Flipbook of CCD Batch 35

Certificate Course on Diabetology (CCD)
Distance Learning Program (DLP)
Batch-35
FLIP BOOK OF DIABETES MELLITUS
Online version, October 2022
For Certificate Course on Diabetology (CCD) Batch-35

Distance Learning Program (DLP)
Diabetic Association of Bangladesh
Editorial Panel
Professor Tofail Ahmed Chief Executive Officer
Dr. Tareen Ahmed Additional Coordinator
Professor S. M. Ashrafuzzaman Assistant Coordinator
Dr. Faria Afsana Assistant Coordinator
Dr. Bishwajit Bhowmik Assistant Coordinator
All rights reserved. No part of this online flipbook may be reproduced or transmitted
in any form or by any means - electronic, mechanical, photocopying, recording or
otherwise - without prior permission of the Distance Learning Program of
Diabetic Association of Bangladesh (BADAS).
Program Chairperson
National Professor A. K. Azad Khan
President, Diabetic Association of Bangladesh (BADAS)
Course Chairperson
Professor Hajera Mahtab
Professor Emeritus, Bangladesh University of Health Sciences (BUHS)
Technical Partner
CT Health Ltd.
Ventura Iconia, Level-3 House-37, Road: 11, Block: H
Banani, Dhaka-1213.
Foreword
The Bangladesh Diabetic Somiti (BADAS)/Diabetic Association of Bangladesh (DAB) is

playing a unique role by organizing diabetic health care throughout the country since its
beginning in 1956. To fulfil the increasing gap of appropriately trained physician to serve
the diabetic population, DAB established DLP in 2003 to run a 6-month Certificate course
called CCD in addition to its activities of formal manpower production by the BIRDEM Acad-
emy. It was in modular format taught in Regional Tutorial Centre (RTC) by tutor. But we
changed the format to a fully online one from the batch-32nd due to pandemic of COVID 19.
In this format the basic study is “Self-study of a Lesson with its online End Lesson Practice”
so we stopped supplying printed text material and introduced a Flip Book for each session.
This system will provide better opportunity to keep peace with more efficient update of
curriculum, changes in evaluation materials like ECE questions etc. This is our 4th Flipbook
and is for the students of batch 35.
We believe the new system adopted justifies more for a Distance Learning Program. We are
very happy to see that our doctors have accepted the new format. We congratulate them
and whish their success.
National Professor Professor Hajera Mahtab Professor Tofail Ahmed

A. K. Azad Khan Course Chairperson, DLP CEO, DLP
Chairperson, DLP
President, BADAS
Content
Phase - A
Module - 1
Introduction and Epidemiology of Diabetes Mellitus
Page
Lesson-1 Objective 3
Lesson-2 Definition of Diabetes Mellitus 3
Lesson-3 Classification of Diabetes Mellitus 4
Lesson-4 Type 1 Diabetes Mellitus 5
Lesson-5 Type 2 Diabetes Mellitus 5
Lesson-6 Other Specific Types of Diabetes Mellitus 6
Lesson-7 Gestational Diabetes Mellitus (GDM) 6
Lesson-8 Diabetes Complications 7
Lesson-9 Treatment of Diabetes 7
Lesson-10 Epidemiology of Diabetes Mellitus 8
Lesson-11 Global trend 9
Lesson-12 South-East Asia trend 10
Lesson-13 Bangladesh and Indian trend 11
Lesson-14 Diabetes in the young 12
Lesson-15 Morbidity and Mortality 13
Lesson-16 Summary 14
Content
Phase - A
Module - 2
Definition, Presentation, Diagnosis andClassification of Diabetes Mellitus
Page
Lesson-2 Definition of DM 16
Lesson-3 Clinical presentation: Asymptomatic 17
Lesson-4 Clinical Presentation: Typical 17
Lesson-5 Clinical presentation: Atypical 18
Lesson-6 Presentation: Complications of DM 19
Lesson-7 Blood (plasma) glucose tests 20
Lesson-8 OGTT: Result interpretation 20
Lesson-9 FPG: Result interpretation 22
Lesson-10 RPG: Result interpretation 23
Lesson-11 HbA1c: Result interpretation 24
Lesson-12 OGTT Procedure 25
Lesson-13 Classification of DM 26
Lesson-14 T1DM 27
Lesson-15 T2DM 28
Lesson-16 T1DM vs T2DM 29
Lesson-17 Secondary DM 29
Lesson-18 Prediabetes 31
Lesson-19 Prediabetes 31
Content
Phase - A
Module - 3
Aetiopathology of Diabetes Mellitus
Page
Lesson-2 Introduction to Aetiopathology 34
Lesson-3 Pancreas 35
Lesson-4 Insulin 36
Lesson-5 Insulin secretion 37
Lesson-6 Tissue & insulin action 38
Lesson-7 Insulin secretion in healthy subjects 39
Lesson-8 Glucose homeostasis during fasting state in healthy subject 40
Lesson-9 Glucose homeostasis after food intake in healthy subjects 41
Lesson-10 Glucose homeostasis during fasting state in healthy subject 42
Lesson-11 Risk factors of diabetes 43
Lesson-12 Pathogenesis of Type 1 DM 44
Lesson-13 Pathogenesis of Type 2 DM 45
Lesson-14 Insulin release in T2DM 46
Lesson-15 Beta cell failure 47
Lesson-16 Insulin resistance & Metabolic syndrome 48
Lesson-17 Incretin, Glucagon, SGLT-2, Brain factors and T2DM 51
Content
Phase - B
Module - 4
General Principles in Management of DM
Lifestyle Modification
Page
Lesson-2 General Principles in Management of DM 55
Lesson-3 Aims and steps of Treatment of DM 57
Lesson-4 Step 1. Diagnosis and 2. Factor Analysis 58
Lesson-5 Step 3. Targets of Treatment 59
Lesson-6 Step 4: Selection & Initiation of a Treatment Regimen 60
Lesson-7 IStep 5: Monitoring & Changing Treatment Regimen 61
Lesson-8 Step 6: Complications Screening, Referral & Step 7: Treatment Evaluation 63
Lesson-9 Lifestyle Modification in DM 63
Lesson-10 MNT in DM 64
Lesson-11 MNT: Calorie Requirement 65
Lesson-12 MNT: Component of Nutrients 66
Lesson-13 MNT: Carbohydrates, Fat & Protein 66
Lesson-14 MNT: Vitamins, Sweeteners & Alcohol 67
Lesson-15 MNT: Weight Management 68
Lesson-16 Meal Timing, Composition and Planning 69
Lesson-17 Anthropometric Measurement 70
Lesson-18 Exercise and DM 71
Lesson-19 Exercise 73
Content
Phase - B
Module - 5
Drug Therapy in Diabetes Mellitus
Page
Lesson-2 Introduction 77
Lesson-3 Oral anti-diabetic drugs (OADs) 78
Lesson-4 Sulfonylureas and Glinides 81
Lesson-5 Metformin & Thiazolidinediones 84
Lesson-6 Alpha-glucosidase inhibitors & DPP-4 inhibitors 85
Lesson-7 SGLT-2 inhibitors & other OADs 87
Lesson-8 Use of OAD 89
Lesson-9 Initiation and dose titration of OADs 91
Lesson-10 Injectable agents 92
Lesson-11 Insulin Therapy 94
Lesson-12 Insulin administration guideline 96
Lesson-13 Insulin administration 97
Lesson-14 Insulin administration guideline 98
Lesson-15 Pancreatic transplant 100
Lesson-16 Diabetic education 101

Content
Phase - B
Module - 6
Acute Complications of Diabetes Mellitus
Page
Lesson-2 Acute complications of DM 104
Lesson-3 DKA & its cause 105
Lesson-4 Clinical feature & diagnosis of DKA 105
Lesson-5 Management (Principle) of DKA 106
Lesson-6 Management of DKA 106
Lesson-7 Complications of DKA 107
Lesson-8 HONK and its Causes 107
Lesson-9 Clinical feature & diagnosis of HONK 108
Lesson-10 Management of HONK 108
Lesson-11 Lactic acidosis 109
Lesson-12 Treatment of Lactic acidosis 110
Lesson-13 Hypoglycemia 110
Lesson-14 Severity of Hypoglycemia 111
Lesson-15 Unaware hypoglycemia and Nocturnal hypoglycemia 112
Lesson-16 Causes of hypoglycemia in a diabetic 113
Lesson-17 Treatment of hypoglycemia 113
Lesson-18 Glycemic management of critically ill patients 115

Content
Phase - B
Module - 7
Microvascular Complications of Diabetes Mellitus
Page
Lesson-3 Factors affecting Microangiopathy 118
Lesson-4 Mechanism of Microangiopathy 119
Lesson-5 Diabetic retinopathy (DR) 120
Lesson-6 Classification of DR 122
Lesson-7 Lesions in different class of DR 123
Lesson-8 Evaluation and Treatment 124
Lesson-9 Other changes in eye 126
Lesson-10 Decision Making Path of DR 127
Lesson-11 Diabetic nephropathy (DN) 127
Lesson-12 Diabetic nephropathy (DN) 128
Lesson-13 Staging of DN 130
Lesson-14 Renal Function evaluation in DM 131
Lesson-15 Treatment of DN 132
Lesson-16 Decision making path of DN 133
Lesson-17 Diabetic Neuropathy 133
Lesson-18 Somatic Neuropathy 135
Lesson-19 Diabetic Neuropathy (Autonomic) 136
Lesson-20 Evaluation of Diabetic Neuropathy 136

Lesson-21 Treatment of Somatic Neuropathy 138
Lesson-22 Treatment of Autonomic Neuropathy 139
Lesson-23 Decision making path of DN 139

Content
Phase - C
Module - 8
Macrovascular Complications of Diabetes Mellitus
Page
Lesson-3 Factors affecting Macroangiopathy 145
Lesson-4 Mechanism of Macroangiopathy 146
Lesson-5 Hypertension 147
Lesson-6 Antihypertensive drugs 148
Lesson-7 Hypertension treatment in DM 149
Lesson-8 Dyslipidemia 150
Lesson-9 Dyslipidema Management 152
Lesson-10 Aspirin use in diabetes 154
Lesson-11 Diabetic foot 155
Lesson-12 High Risk Foot 157
Lesson-13 Foot care education for diabetics 158
Lesson-14 How to choose footwear for a person with diabetes? 159
Lesson-15 Oral and skin care 160

Content
Phase - C
Module - 9
Diabetes Mellitus in Young and Older People
Hyperglycemia in Pregnancy
Page
Lesson-2 DM in the Young 163
Lesson-3 Screening for diabetes in children 164
Lesson-4 Principles of diabetes management in childhood 165
Lesson-5 MNT and drugs DM in Children 166
Lesson-6 Diabetes education for Yong Diabetic 167
Lesson-7 Hypertension and Dyslipidemia in Children 168
Lesson-8 DM in the older people 169
Lesson-9 MNT and Physical activity in Older people 170
Lesson-10 Drug treatment of DM in Older people 170
Lesson-11 Acute emergencies and Co-morbidities 171
Lesson-12 Hyperglycemia (DM) and Pregnancy 172
Lesson-13 DM and pregnancy: Forms & problems 173
Lesson-14 Pre-pregnancy diabetes 174
Lesson-15 GDM and its screening 174
Lesson-16 Diagnosis of GDM 175
Lesson-17 Targets and Check up schedule 176
Lesson-18 Lifestyle and drugs treatment 177
Lesson-19 Delivery & Hypoglycemia of Newborn 178

Content
Phase - C
Module - 10
Diabetes Mellitus in Special Situations
Prevention of Diabetes Mellitus
Page
Lesson-2 DM in special situations 182
Lesson-3 Surgery and DM 183
Lesson-4 General principles of management (Steps 1 & 2) 184
Lesson-5 General principles of management (Steps 3,4 & 5) 185
Lesson-6 Specific strategies of Surgery with DM 186
Lesson-7 Strategies for poorly controlled DM and emergency 187
Lesson-8 DM management on Sick days 188
Lesson-9 Ramadan Fasting and Diabetes Mellitus 189
Lesson-10 Categories of risk in DM for Ramadan 190
Lesson-11 Management of diabetes during Ramadan 191
Lesson-12 Specific measures for T2DM & T1DM 192
Lesson-13 Prevention of DM 193
Lesson-14 Primary prevention 194
Lesson-15 Approach to Prevention of DM 195
Lesson-16 Secondary prevention of DM 197
Lesson-17 Tertiary prevention of DM 198
Lesson-18 Epidemological Aspect of Tuberculosis and Diabetes 200
Lesson-19 Tuberculosis and Diabetes: presentation, Clasification & Diagnosis 201

Lesson-20 Tuberculosis And Diabetes: Treatment 204
Phase-A
Module-1: Introduction and Epidemiology of

Diabetes Mellitus
Module-2: Definition, Presentation, Diagnosis and
Classification of Diabetes Mellitus
Module-3: Aetiopathology of Diabetes Mellitus
1
Module-1
Introduction and Epidemiology

of Diabetes Mellitus
2
P-A M-1 L-1 P-A
Objective
M-1 L-1
Through this module activity, you will be able to
• Define and classify diabetesmellitus.

• Understandwhatismeantbyprevalencerateofdiabetesmellitusandhowitisestimated.
• Explain why there are differences in prevalence rate of diabetes mellitus indifferent
places and in same place at different times.
P-A M-1 L-2 Definition of Diabetes Mellitus
Diabetes mellitus is defined as chronic/persistent hyperglycemia, due to deficiency of

insulin secretion, or of insulin action, or both. Several pathological processes are involved
in causing diabetes. These processes are regulated by genetic and/or environmental
factors.
Three parts of definition
Biochemical Hallmark Physiological Changes Pathological Process
Diabetes mellitus is Deficiency of insulin Several pathological

defined as chronic/per- secretion, processes are involved in
sistent hyperglycemia. Deficiency of insulin causing diabetes.
action or The processes are regu-
Both. lated by genetic and/or
environmental factors
3
P-A M-1 L-3 Classification of Diabetes Mellitus
Diabetes mellitus is classified into four types/classes on the basis of aetiology.
DM: Classification
1. Type 1 diabetes mellitus (T1DM)
2. Type 2 diabetes mellitus (T2DM)
3. Gestational diabetes mellitus (GDM)
4. Other specific types or secondary diabetes mellitus (20DM)
Four classes of DM: on the basis of aetiology
1. Type 1 DM 2. Type 2 DM
Destruction of beta-cells by autoimmune Defect in insulin secretion and/or action
process leading to insulin secretion nil. produced by genetic and/or environmen-
tal factors.
3. GDM 4. Other specific types or Secondary DM

Women identiﬁed to have Glucose Defect in insulin secretion and/or action
Intolerance during pregnancy and is in individual with known disease, drugs
usually due to defect of insulin action. or genetic condition /syndrome.
4
P-A M-1 L-4 Type 1 Diabetes Mellitus
T1DM
Type 1 diabetes (also previously called ‘insulin dependent diabetes/juvenile onset
diabetes') occurs due to destruction of the insulin producing beta cells of the islets of
Langerhans of pancreas by auto-immune mechanism. At the time of onset of diabetes,
there is little or no insulin in the body. Some environmental factors trigger the autoim-
mune reaction in genetically susceptible individuals. This type of diabetes can affect
people of any age, but usually occurs in children or young adults. The onset is often
sudden and symptoms are florid.
T1DM: Important features

Pathophysiology of T1DM Factors of T1DM Some other features of T1DM
Auto-immune destruction of Environmental factors trigger • Usually occurs in children or
the insulin producing beta cells the autoimmune reaction in young adults.
of the islets of Langerhans. genetically susceptible individ- • The onset is often sudden
There is little or no insulin in uals. and symptoms are florid
the body at the time of onset of
diabetes.
P-A M-1 L-5 Type 2 Diabetes Mellitus
T2DM
Type 2 diabetes constitutes major portion of diabetic population. This type of diabetes
occurs due to insulin resistance and relative insulin deficiency, usually develops with
increasing age (previously called ‘non-insulin dependent diabetes/maturity onset diabe-
tes’). Environmental factors like obesity and physical inactivity are known strong deter-
minants in genetically susceptible individuals. This type of diabetes usually passes
through pre-diabetic stage (Impaired Fasting Glucose-IFG and Impaired Glucose Toler-
ance-IGT). At diagnosis a large number of cases of T2DM remain asymptomatic and
often present with diabetic specific complications.

Pathophysiology of T2DM Factors of T2DM Some other features of T2DM
Diabetes occurs due to insulin Environmental factors like • This type of diabetes usually
resistance and relative insulin obesity and physical inactivity passes through pre-diabetic
deficiency, usually develops are known strong determinants stage (Impaired Fasting
with increasing age. in genetically susceptible Glucose-IFG and Impaired
individuals. Glucose Tolerance-IGT).
• At diagnosis a large number
of cases of T2DM remain
asymptomatic and often
present with diabetic specific
complications.
5
P-A M-1 L-6 Other Specific Types of Diabetes Mellitus
20 DM
Some specific diseases, drugs or genetic conditions/syndromes are associated with
development of chronic hyperglycemia. These forms of diabetes are classified as other
specific types of diabetes mellitus.
Occurs in persons with known disease, drugs or genetic condition/syndrome associat-
ed with secretion and/or action defect of insulin. Causes include:
• Endocrinopathies
• Drugs & toxins
• Pancreatic disease etc
20DM: Important features

Pathphysiology of 20DM Factors of 20DM Some features of 20DM
Occurs in persons with known Known factors like This type of diabetes has
disease, drugs or genetic • Endocrinopathies • Features primary condition
condition/syndrome associat- • Drugs & toxins and
ed with secretion and/or action • Pancreatic disease etc • Features related to diabetes.
defect of insulin.
P-A M-1 L-7 Gestational Diabetes Mellitus (GDM)
GDM
GDM is glucose intolerance of any degree which starts or is recognized during pregnan-
cy. Maintaining blood glucose very tightly reduces the risk to the mother and the baby.
Special points to be noted that GDM is glucose intolerance of any degree which is
recognized during a pregnancy; when the pregnancy is over and glucose intolerance
returns to normal then this GDM becomes her past medical history; otherwise she will
be named according to the degree of glucose intolerance i.e. IFG, IGT or DM.

Pathophysiology of GDM Factors of GDM Some features of GDM
GDM is glucose intolerance of Known factors are Pregnancy outcome is bad
any degree which starts or is • Age, Obesity, Family history • For Mother and
recognized during pregnancy. of DM and Bad obs. history. • For Baby.
So hormones released by
placenta have pathophysiolog-
ic link.
6
P-A M-1 L-8 Diabetes Complications
20 DM
Uncontrolled diabetes mellitus sets in an abnormal state in metabolism in the body.

Therefore, all tissues/organs of the body are in threat of developing complications of
diabetes. Long term complications are mediated by microvascular and macrovascular
changes.
• A diabetic is at risk of developing coronary artery disease, stroke, blindness, renal
failure, lower limb amputation etc. many times more than a non-diabetic person.
• Children with uncontrolled diabetes may have problem in growth.
• Pregnancy in women with diabetes threatens both expectant mother and foetus.
• Acute metabolic derangement may lead to life threatening diabetic comas, such as
diabetic ketoacidosis (DKA), hyperosmolar non-ketotic coma (HONK) etc.
Diabetic Complications
Uncontrolled DM is key to complication Long term complications Acute metabolic derangement
Uncontrolled DM sets in an Long term complications are Acute metabolic derangement
abnormal state in metabolism mediated by may lead to life threatening
and thereby all tissues/organs • microvascular and diabetic comas such as DKA,
of the body are in threat of • macrovascular changes. HONK etc
developing complications of
diabetes.
P-A M-1 L-9 Treatment of Diabetes
Treatment of DM
Treatment of diabetes mellitus is to achieve some specific goals. "Treating to target"
provides effective prevention of diabetic complications.
• The primary goal is the control of high blood glucose.
• Other goals includes:
1. Management of co-existing disease conditions (hypertension, dyslipidemia)
2. Modification of risk factors (obesity, physical inactivity) and
3. Screening for early detection of chronic complications.
Treat to Target
Goals of DM treatment Target based treatment Diabetes Education (DE)
1. Control of high blood Treating to target provides Diabetes education to the
glucose, effective prevention of diabetic patients and their families is
2. Management of co-existing complications. essential for cost effective
disease conditions, treatment
3. Modification of risk factors
and
4. creening for early detection
of chronic complications.
7
P-A M-1 L-10 Epidemiology of Diabetes Mellitus
PREVALENCE OF DM
The prevalence rate of diabetes mellitus varies in different places and in same place at
different times. Epidemiological studies called survey or surveillance are done to under-
stand this phenomenon of DM.
• Epidemiological evidences suggest that number of diabetics is increasing worldwide.
In some parts of the world it is alarmingly high.
• It is putting tremendous burden on medical, economic and social infrastructure.
• There are evidences that low and middle-income countries will face the greatest
burden of diabetes.
• Nearly 50% diabetic cases remain undiagnosed
• The change in prevalence rate of DM is due to the change of risk factors in the
population.
• The risk factors of diabetes mellitus are assessed by epidemiological tools called
survey and surveillance study.
PREVALENCE OF DM
Definition of Prevalence Formula of Prevalence Formula of Prevalence Increased
It is the number of persons Prevalence = (Number of Prevalence Increased = [(Pre-
suffering form DM per 100 affected persons x 100) / Total sent Prevalence - Previous
persons in a defined popula- number of population. Preva- lence) x 100] / Previous
tion at a certain time. Preva- lence].
Examples OF DM
PREVALENCE
Prevalence of diabetes mellitus
In a survey in 2009 (time) 800 city dwellers of Dhaka, aged 20 to 79 years (population),
tested for diabetes mellitus and 64 persons were suffering from diabetes mellitus.
Therefore, prevalence of diabetes mellitus documented as 8.0%. [(Number of DM
persons x 100) / Total number of persons tested].
Prevalence increased
8
P-A M-1 L-11 Global trend
Diabetes mellitus is now one of the most common non-communicable diseases globally.
It is epidemic in many developing and industrialized countries. China and India hold the
1st and 2nd positions respectively having 114 and 73 millions of total cases of diabetes
in adult population (20 to 79 years) in 2017.In addition to diabetes, IGT also constitutes a
major public health problem, both because of its association with diabetes incidence and
its own association with an increased risk of cardiovascular disease.
Type 2 diabetes constitutes about 90% of all diabetes. This increasing trend of type 2
diabetes is associated with changing lifestyle such as increasing urbanization, dietary
changes, reduced physical activity along with population aging.
Type 1 diabetes usually accounts for only a minority of total burden in a population.
Now-a-days it is also increasing. High incidence is seen in Finland, Sweden, Denmark,
Norway and UK.
Global estimate of DM and IGT

2017 2045
Total world population (billions) 7.5 9.5
Adult population (20-79 years, billions) 4.8 6.4
DM in adult population
Prevalence (%) 8.8 9.9
Number of people with DM (millions) 425 629
IGT in adult population
Number of people with IGT (millions) 352 532
In 1985 another similar survey documented the prevalence of diabetes mellitus was
5.3%. So, the prevalence of diabetes increased among the Dhaka city dwellers by
50.94% [{(Present Prevalence - Previous Prevalence) x 100}/
Previous Prevalence] in 24-year time.
Almost two thirds of the diabetics are between the ages of 20 and 64 years, with slight
predomi- nance of males.
Prevalence of diabetes and IGT in 7 IDF regions are shown in the figure: Africa (AFR),
Europe (EUR), Middle East and North Africa (MENA), North America and Caribbean (NAC),
South and Central America (SACA), South-East Asia (SEA) and Western Pacific (WP).
9
Prevalence of DM by age & Sex (Time 2015) Prevalence of DM in seven IDF regions
(Time 2015 & projected for 2040)
Africa (AFR), Europe (EUR), Middle East

and North Africa (MENA), North America
and Caribbean (NAC), South and Central
America (SACA), South- East Asia (SEA)
and Western Pacific (WP)
P-A M-1 L-12 South-East Asia trend
South-East Asian Region is one of the most populous regions in the world. Bangladesh
and India are situated in this region. Nearly one-fifth of all diabetics live in this region.
Estimate of DM and IGT in South-East Asia Region

2017 2045
Adult population (20-79 years, millions) 962 1370
DM in adult population
Number of people with DM (millions) 82 151
IGT in adult population
Number of people with IGT (millions) 29 50
10
SEA trend of DM
Number of people suffering from DM in SEA region is also increasing.

• Prevalence of T2DM in adult population (20 to 79 years) was 8.2% in 2013 and 8.5% in
2015 and total number people with DM were 72.1 millions and 78 millions respectively.
• Prevalence of IGT in adult population in 2015 was 4.6% and total number people with
IGT was 42.2 millions.
• Number of Type 1 DM children in 2015 was (0-14 years) 81,400.
• Approximately 1.2 millions people of age 20-79 years died from diabetes in 2015.
• Diabetes accounts for 53.2 % of mortality among the people under 60 years of age.
Prevalence of DM by age & Sex Prevalence of DM by 7 member countries

(Time 2015) in SEA region (Time 2015)
Bangladesh 7.4 [5.5 - 12.5]
Bhutan 7.9 [7.0 - 9.3]
India 8.7 [7.0 - 10.6]
Maldives 7.5 [6.1 - 9.9]
Mauritius 24.3 [21.1 - 28.0]
Nepal 3.3 [2.3 - 9.5]
Sri Lanka 8.5 [6.1 - 12.9]
P-A M-1 L-13 Bangladesh and Indian trend
Magnitude of DM in Bangladesh and India are also increasing. The table below summariz-
es the issue.
11
2017 2017 2045 2045
India and Bangladesh at a glance
(India) (Bangladesh) (India) (Bangladesh)
Diabetes estimates (20-79 years)
Country prevalence, % 8.8 (6.7-10.9) 6.9 (5.6-9.5) 11.4 (8.8-14) 9.4 (7.8-12.8)
Age-adjusted comparative prevalence,% 10.4 (8-12.9) 8.4 (6.8-11.6) 10.4 (8.1-12.9) 8.4 (6.8-11.6)
Number of people with diabetes, 72,946.4 6,926.3 134,298.2 134,298.2

in 1,000s (55,473-90,198.1) (5,628.9-9,513.4) (103,390.8-165,171.9) (103,390.8-165,171.9)
Number of people with undiagnosed 42,210.3 3,878.7 77,711.4 7,649.2

DM, in 1,000s (32,099.4-52,193) (3,152.2-5,327.5) (59,826.9-95,576.5) (6,313.3-10,395.7)
Proportion of undiagnosed cases, % 57.9 56 57.9 56
P-A M-1 L-14 Diabetes in the young
Diabetes in the young

• Rapidly increasing in children and adolescents in many countries.
• The overall annual increase is estimated to be around 3%.
• Total number of type 1 diabetics globally is over 11,00,000.
• Numbers of newly diagnosed cases per year are 132,600 and 19,500 across the globe
and SEAR respectively (<20 years)
• In Bangladesh the incidence is 17.1 per 1000 population.
• Type 2 diabetes in children and adolescents is also increasing in all countries, and
evidence suggests that in a growing number of countries type 2 diabetes is now also
12
P-A M-1 L-15 Morbidity and Mortality
Morbidity and mortality

• Diabetes is one of the major causes of premature illness and death in most countries.
Cardiovascular diseases, resulting from damage to large blood vessels, cause death of
50% or more for people with diabetes depending on the population. At least one compli
cation will be present in 50% of newly detected diabetes cases. Around 4 million deaths
related to diabetes were reported globally in 2017.
• The SEA Region was estimated to have the second highest number of deaths due to
diabetes of all the regions in 2017. An estimated 1.1 million adults were expected to die
from diabetes-related causes accounting for 14.0% of all deaths in the 20-79 years’ age
group, where the global figure was 10.7%.
13
P-A M-1 L-16 Summary
There are 14 Lessons in Module 1. I understand the following points:

• DM is defined as chronic/persistent hyperglycemia due to deficiency of insulin
secretion, or of insulin action, or both
• There are 4 classes of DM based on aetiology - T1DM, T2DM, GDM and Other
specific types.
• Prevalence of DM in a defined population at a certain time is the number of persons
with DM per 100 persons.
• There are some risk factors of DM. Prevalence of risk factors in a population changes
with time, and also is different for other populations.
• Prevalence of DM in a population is a changing parameter.
• Survey or surveillance study are used to determine risk factors and prevalence of DM
in populations.
Further reading
1. Textbook of Diabetes, 4th edition, edited by Richard I G Holt, Clive S Cockram, Allan
Flyvbjerg & Barry J Goldstein, Wiley-Blackwell, 2010.
2. Diabetes Atlas, 8th edition, IDF (International Diabetes Federation), 2017.
14
Module-2
Definition, Presentation,
Diagnosis and Classification
of Diabetes Mellitus
15
P-A M-2 L-1 Objective
Through this module activity, you will be able to:
• Define diabetes mellitus.

• Describe the clinical presentation of diabetes mellitus.
• Supervise the procedure for OGTT.
• Interpret blood glucose values and HbA1c for diagnosis of diabetes, IGT and IFG
P-A M-2 L-2 Definition of DM
Diabetes mellitus must be diagnosed by blood glucose test. Many cases, especially vast
majority of Type 2 diabetes, present without symptom. Whether present with symptom or
not, there are standard criteria for diagnosis based on World Health Organization (WHO)
and American Diabetes Association (ADA) recommendations. Similarly, there is an aetio-
logical classification of diabetes which is being used universally.
• Diabetes mellitus is a metabolic disorder resulting in raised blood glucose
(hyperglycemia).
• Diabetes mellitus results from defects in insulin secretion, insulin action, or both
that arise from genetic as well as environmental factors.
• It is defined by documenting raised blood glucose in fasting state (>7.0 mmol/L)
and/or two hours after a standard oral glucose drink (>11.1 mmol/L).
DIABETES MELLITUS (DM)

Hallmark of DM Pathophysiology of DM Diagnostic criteria of DM
DM is a metabolic disorder DM results from DM is defined by documenting
raised blood glucose
• Resulting in raised blood • Defects in insulin secretion,
glucose hyperglycemia insulin action, or both • In fasting state >7.0 mmol/L
• Defects arise from genetic
as well as environmental • And/or two hours after a
factors standard oral glucose drink
>11.1 mmol/L
16
P-A M-2 L-3 Clinical presentation: Asymptomatic
There are 4 different types of presentations
1 2 3 4
Asymptomatic Typical features Atypical features Complications of DM
• A vast majority of asymptomatic DM belong T2DM. They remain asymptomatic until

blood glucose persistently remains above the renal threshold
(approximately 10 mmol/L).
• GDM and other specific types of DM can have asymptomatic presentation but T1DM
does not have this type of presentation.
• Asymptomatic cases are diagnosed by biochemical test only.
• Routine check-up usually picks up this form of diabetes
Asymptomatic diabetes mellitus
Diagnosed by biochemical test only.
Most cases are picked up by routine check-up.
Type 2 DM, GDM and other specific types of DM can have asymptomatic phase.
Type 1 DM usually does not have this form of presentation.
P-A M-2 L-4 Clinical Presentation: Typical
1 2 3 4
Typical features start with ‘glycosuria’ which means passage of glucose in urine that
begins after the blood glucose level has gone above individual’s renal threshold for
glucose.
17
Features are
• Polyuria, meaning increased urination
• Polydipsia, meaning increased thirst
• Polyphagia, meaning increased hunger
• Weight loss
• General weakness
Diabetes mellitus with typical features
Polyuria, Polydipsia, Polyphagia, Weight loss and General weakness are the 5
features (3Ps+ 2Ws)
Type 1 DM always present with typical features.
Type 2 DM, GDM and other specific type of DM can have typical presentation.
P-A M-2 L-5 Clinical presentation: Atypical
1 2 3 4
• Atypical manifestations are non-specific. A short list includes:

• Non-healing infection
• Infertility or repeated pregnancy loss
• Undue fatigability
Diabetes mellitus with atypical presentation
Diagnosed during evaluation of conditions which are not specific for diabetes.
Except in specific conditions, most diabetic cases fall in the group of asymptomatic
and atypical presentation.
As a class or type they mostly belong to type 2 DM, GDM and other specific type of DM.
18
P-A M-2 L-6 Presentation: Complications of DM
1 2 3 4
• Diabetes and its chronic complications are present at the time of diagnosis.
• T2DM and other specific types show this type of presentations, because they may
remain asymptomatic for quite a long period after the start of diabetes.
• A significant proportion of T2DM cases present with one or more features related to
diabetic specific chronic complications.
• The complications are micro- and macroangiopathies.
• In T1DM, from the start of DM there is total lack of insulin. So presentation will be
almost always typical and florid, but there will be no chronic complications.
DM diagnosed with its Complication

DM detected along with its chronic complication(s).
Microvascular complication(s) may be diabetic retinopathy, nephropathy and/or

neuropathy.
Macrovascular complication(s) may be coronary artery disease, cerebrovascular

disease and/or peripheral vascular disease.
Type 2 DM shows more of this type of presentation and type 1 DM does not have this
form of presentation.
19
P-A M-2 L-7 Blood (plasma) glucose tests
Blood glucose assay in three different tests

Blood glucose assay is done by glucose oxidase
method using auto-analyzer from plasma. It is
done during three tests.
1. Oral Glucose Tolerance Test (OGTT)
2. Fasting Plasma Glucose (FPG)
3. Random Plasma Glucose (RPG)
Three tests
OGTT FPG RPG
• Gold standard test • May miss diagnosis of IGT & • Can suspect (mostly
DM
P-A M-2 L-8 OGTT: Result interpretation
Three tests
OGTT FPG RPG
• Gold standard test • May miss diagnosis of IGT & • Can suspect (mostly
DM
OGTT is the ideal procedure to confirm glucose intolerance.

In this procedure two blood (plasma) glucose levels are determined
1. At fasting and
2. At 120th minute after 75 grams of oral glucose drink
Interpretation of the two blood glucose values of a person can be categorized in one of
4 categories. DM (diabetic), IGT (Impaired Glucose Tolerance), IFG (Impaired Fasting
Glucose), or normal. IGT and IFG together are called Pre-diabetes.
20
1. A person is normal if FPG <6.1 (*5.6) mmol/L and AG <7.8
mmol/L
2. A person is diabetic if FPG =/>7.0 mmol/L or/and AG =/>11.1
mmol/L
3. A person is having Impaired Fasting Glucose (IFG) if FPG 6.1
(*5.6) to 6.9 mmol/L and AG <7.8 mmol/L
4. A person is having Impaired Glucose Tolerance (IGT) if FPG
<7.0mmol/L and AG 7.8 to <11.1mmol/L
Blood (plasma) glucose Normal IFG IGT Diabetes
FPG (mmol/L) <6.1 (*5.6) 6.1 (*5.6) to 6.9 <7.0 >7.0
and and and or/and
After glucose (mmol/L) <7.8 <7.8 7.8 to <11.1 >11.10

NB: * American Diabetes Association (ADA) criteria only; all others WHO & ADA criteria.
Interpretation of OGTT result
Blood glucose curve during OGTT Interpretation of diagnostic test results
Pre-diabetes (IFG+IGT) = Impaired HbA1c%, FBG & 2nd Sample of OGTT
21
P-A M-2 L-9 FPG: Result interpretation
Three tests
OGTT FPG RPG
• Gold standard test • May miss diagnosis of • Can suspect (mostly
IGT & DM
By Fasting Plasma Glucose level, a person can be labeled as

• Diabetic (DM) if it is at or above a set value.
• Normal Fasting Glucose (NFG) if it is below one set value.
• If FPG lies in between the two set values inference is Impaired Fasting Glucose (IFG)
FPG
• A person can be labeled as DM if it is at or above 7.0 mmol/L
• A person is labeled as a Normal Fasting Glucose (NFG) if it is below 6.1 mmol/L.
• If FPG lies in between 6.1 and 6.9 mmol/L he/she is labeled as Impaired Fasting
Glucose (IFG).
Blood glucose Normal IFG IGT
FPG (mmol/L) <6.1 (*5.6) 6.1 (*5.6) to 6.9 <7.0 Diabetes
NB: * 5.6 mmol/L (as per American Diabetes Association – ADA). FPG can denote one
as Diabetic or IFG but not as Normal. A person of either NFG or IFG, if subjected to
OGTT, may be found as Diabetic or IGT.
FPG
22
P-A M-2 L-10 RPG: Result interpretation
Three tests
OGTT FPG RPG
• Gold standard test • May miss diagnosis of • Can suspect (mostly
IGT & DM
RPG
• No preparation is required for this procedure.
• Blood (plasma) glucose levels are estimated from a sample, irrespective of
last meal.
• RPG can suspect diabetes; but often falls in uncertain range.
• So such test result should be interpreted on the clinical background and very
often demands OGTT for subjects in uncertain range
Random Plasma Glucose (RPG)

• RPG can suspect diabetes if it is >11.1 mmol/L (+Symptoms of hyperglycemia).
• RPG often falls in uncertain range (5.5 to <11.1 mmol/L).
• RPG <5.5 mmol/L - inference is DM is unlikely.
Interpretation of RPG result)
Blood glucose DM is unlikely Uncertain zone DM is likely

>11.1 (+Symptoms of
RPG (mmol/L) <5.5 5.5 to <11.1
hyperglycemia)
23
P-A M-2 L-11 HbA1c: Result interpretation
Tests: Blood glucose & HbA1c
Blood glucose HbA1c
• Hba1c is now increasingly being used in

diagnosis of diabetes.
• The test must be highly standardized for
using it in this purpose.
• It can be done any time.

• Yet it is not available easily and also costly.
• It can guide to select treatment regime at diagnosis.
HbA1c%
• A person is diabetic if HbA1c is 6.5 % or more.

• A person is pre-diabetic (IFG/IGT) if HbA1c is 6.0 to 6.4%.
• A person is normal if HbA1c is <6.0%
Interpretation: HbA1c
HbA1c DM Pre- diabetes Normal
% >6.5 6.0*-6.4 <6.0*
NB: * American Diabetes Association (ADA) use 5.7%.
HbA1c
24
P-A M-2 L-12 OGTT Procedure
Some important points related to OGTT procedures
Reporting
Points
Fasting state • The test should begin in the morning after 8-14 hours of
overnight fast.
Carbohydrate in meals • Person should take unrestricted diet containing at least

prior to the test 150 grams of carbohydrate daily for at least previous 3
days.
Blood samples and glucose drink

Events
First blood sample • A fasting blood sample prior to glucose drink is collected.
Glucose drink • An oral glucose load of 75 gm for adult (1.75 gm/kg

body weight, up to maximum 75 gm for child) is given in
250-300 ml of water.
• The drink must be completed within 5minutes.
Second blood sample • A blood sample is collected at 120th minute after the
glucose drink. If glucose is not estimated immediately then
the blood sample may be preserved with sodium fluoride (6
mg/ml whole blood).
• Blood should be centrifuged, and plasma separated and
frozen until estimation.
• Smoking, tea or physical stress is not allowed during the
test.
Blood samples and glucose drink

• Glucose in urine (glycosuria) informs us that blood glucose of the person has
crossed his/her renal threshold for glucose.
• Other than diabetes, glycosuria may occur during pregnancy, in renal glycosuria or
alimentary glycosuria etc.
• So, it is not a diagnostic parameter of diabetes.
25
P-A M-2 L-13 Classification of DM
There are 4 different classes. Classification is based on aetiology
Four classes
1 2 3 4
Type1 diabetes Type2 diabetes Gestational diabetes Other specific types or
mellitus (TIDM) mellitus (T2DM) mellitus (GDM) Secondary DM (20 DM)
Four classes of DM: on the basis of aetiology

1.Type 1 DM 2.Type 2 DM
Autoimmune destruction of beta cells Genetic and/or environmental factors
producing secretion of insulin to nil producing secretion and/or action defect
of insulin.
3. GDM 4. Other specific types or Secondary DM
Autoimmune destruction of beta cells Genetic and/or environmental factors

producing secretion of insulin to nil producing secretion and/or action defect
of insulin.
26
P-A M-2 L-14 T1DM
There are 4 different classes. Classification is based on aetiology.
T1DM
Type 1 diabetes, also previously called ‘insulin dependent diabetes (IDDM)’/‘juvenile
onset diabetes’.
• It occurs due to destruction of the insulin producing beta cells of the islets of
Langerhans of pancreas by auto-immune mechanism.
• From the time of onset of diabetes, there is little or no insulin in the body.
• Some environmental factors trigger the autoimmune reaction in genetically
susceptible individuals.
T1DM: important features

Pathophysiology of T1DM Clinical features of T1DM Treatment of T1DM
• Destruction of the insulin • This type of diabetes can • Patients with type 1 diabetes
producing beta cells of the affect people of any age, but are dependent on insulin to
islets of Langerhans of pancre- usually occurs in children or survive, so previously they were
as by auto-immune mecha- young adults. called ‘Insulin Dependent
nism. • Usually the people are lean. Diabetes Mellitus’ (IDDM).
• There is little or no insulin in • The onset is often sudden
the body. and symptoms are florid.
• Environmental and genetic
factors are responsible.
27
P-A M-2 L-15 T2DM
T2DM
Type 2 diabetes constitutes major portion of diabetic population.
• This type of diabetes occurs due to insulin resistance and relative insulin deficiency,
usually develops with increasing age (previously called; non-insulin dependent
diabetes’/‘maturity onset diabetes’).
• Environmental factors like obesity and physical inactivity are known strong
determinants in genetically susceptible individuals.
• This type of diabetes usually passes through pre-diabetic stage (Impaired Fasting
Glucose- IFG and Impaired Glucose Tolerance-IGT). At diagnosis a large number of
cases of T2DM remain asymptomatic and often present with diabetic specific
complications.
T2DM: important features

Pathohysiology of T2DM Clinical features of T2DM Treatment of T2DM
• It is associated with both • It occurs more often in older • Improvement occurs with
impairment of insulin secretion people who are obese and lead weight reduction, balanced diet
and resistance to insulin action sedentary lifestyles. and increased exercise.
(insulin resistance).
• The onset of symptoms is • Oral agents, and in advanced
• Type 2 diabetes is often slower and the disease may go cases, insulin may be required.
associated with a strong undiagnosed for many years.
genetic predisposition, more so
than type 1 diabetes.
28
P-A M-2 L-16 T1DM vs T2DM
The two major classes of DM: T1DM & T2DM can be clinically differentiated.
See the following table.
T1DM vs T2DM
The two major classes can be clinically different in many ways
Points T1DM T2DM
Age of onset < 30 years > 30 years
Body habitus Normal to wasted Obese/overweight
Acute complications DKA HONK/HHS
Symptoms Sudden, typical Gradual, atypical
Insulin therapy Mandatory May be required
Sulphonylurea therapy Unresponsive Responsive
Insulin reserve Absent Normal to high
Markers of beta cell destruction Present Absent
Genetic link Less, HLA link More
P-A M-2 L-17 Secondary DM
Secondary DM
• Some specific diseases, drugs or genetic conditions/syndromes are associated with
development of chronic hyperglycemia. These forms of diabetes are classified as
Other Specific Types of diabetes mellitus.
• Occurs in persons with known disease, drugs or genetic condition/syndrome
associated with secretion and/or action defect of insulin.
29
20DM: important features
Pathohysiology of 20DM Treatment of 20DM Some features of 20DM
• Occurs in persons with • Simultaneous treatment of • This type of diabetes has
Known disease, drugs or DM & primary condition. Features primary condition and
genetic condition/syndrome.
• Features related to diabetes.
• Risk factors: Endocrinopa-
thies, drugs & toxins, pancreat-
ic disease etc.
Some examples of other specific types of DM

Pancreatic
Endocrinopathies Drugs & toxins Others
diseases
• Cushing’s syndrome • Glucocorticoids • FCPD • Genetic defects of
• Acromegaly • ACTH • Chronic or recurrent the beta cell function
• Thyrotoxicosis • Diazoxide pancreatitis • Genetic defects in
• Hyperaldosteronism • Diuretics • Haemochromatosis insulin action
• Pheochromocytoma • Phenytoin • Infections
• Pentamidine • Uncommon forms
• Vacor of immune-mediated
diabetes
• Other genetic
syndromes
30
P-A M-2 L-18 Prediabetes
GDM
• GDM is glucose intolerance of any degree which starts or is recognized during
pregnancy.
• Age, obesity, family history of DM and bad obstetric history.
• Now-a-days universal screening to diagnose GDM cases and very tight glycemic
control is advocated to reduce the
• risk to mother and baby.
GDM: important features

Pathohysiology of GDM Treatment of GDM Some features of GDM
• GDM is glucose intolerance • Very tight glycemic control • A significant portion of the
of any degree which starts or is by MNT + insulin improve GDM cases become normal
recognized during pregnancy. pregnancy outcome. afterwards.
• Age, obesity, family history • Even if GDM becomes

of DM and bad obs. History are normal, the mother has
independent risk factors. increased risk of developing
GDM in subsequent pregnan-
cies.
• Children of GDM mother

have increased risk of becom-
ing a diabetic earlier than
others.
P-A M-2 L-19 Prediabetes
Prediabetes
• Prediabetes has high risk of development of diabetes (25% IFG and 30% IGT cases
become diabetic overtime).
• Prediabetes may develop cardiovascular diseases.
• With lifestyle modifications and drugs may revert 40% of IFG and 30% IGT
cases to normal.
31
Prediabetes = IGT+IFG
Prediabetes Forerunner of T2DM Treatment of prediabetes
• IGT and IFG are referred as • Any diabetes can pass • With lifestyle modifications
‘Prediabetes’. through prediabetic stage, but and drugs use may revert to
it is most obvious in T2DM. normal.
• Prediabetes have high risk of
development of diabetes • Obesity correction & physical
activity are the 2 effective
• Important cardiometabolic tools.
risk factors - obesity, dyslipid-
emias, hypertension etc.
There are 18 Lessons in this Module 2. I understand the following points:

• DM of an individual is diagnosed by his/her FPG >7.0 mmol/L and/or two hours after a
standard oral glucose drink - AG >11.1mmol/L
• There are 4 types of clinical presentations of DM - 1. Asymptomatic, 2.Typical, 3. Atypi
cal or 4. Specific diabetic complications.
• I know how to supervise an OGTT and interpret its result, and also that of HbA1c.
• DM is classified on the basis of aetiology. There are 4 classes of DM: 1. T1DM,
2. T2DM, 3. GDM and 4. Other specific types.
Further Reading
1. Standards of Medical Care in Diabetes, ADA (American Diabetes Association), 2021.
2. Diagnosis and Classification of Diabetes Mellitus and Intermediate Hyperglycemia,
Report of a WHO (World Health Organization)/IDF (International Diabetes Federation),
2006.
3. Global Guideline for Type 2 Diabetes, Clinical Guidelines Task Force, IDF (International
Diabetes Federation), 2012.
32
Module-3
Aetiopathology of Diabetes Mellitus
33
P-A M-3 L-1 Objective
Through this module activity, you will be able to:

• Describe the relationship between blood glucose and insulin in healthy people.
• Discuss insulin actions.
• Discuss consequences of insulin lack and insulin resistance in diabetes.
• Identify the factors (modifiable and non-modifiable) associated in a diabetic person.
• Describe pathogenesis of diabetes mellitus
P-A M-3 L-2 Introduction to Aetiopathology
• Diabetes mellitus primarily affects the carbohydrate metabolism; but it also affects
protein and fat metabolism.
• The disturbed metabolism is due to defects in insulin secretion or insulin action
or both.
• The causes and events related to defects of insulin secretion and action rest on
genetic susceptibility and are aggravated by some environmental factors.
• There are some other pathological processes that have been implicated in
diabetes in recent time.
• Understanding both physiological and pathological events are fundamental to the
understanding of the disorder for appropriate management strategies.
Aetiopathology of DM
DM is metabolic disorder Factor of DM development Other factors
• Primarily affects the carbo- • Defects in insulin secretion Abnormalities of
hydrate metabolism; or insulin action or both.
• Glucagon,
• But it also affects protein • Defects are due to genetic • Incretins,
and fat metabolism. susceptibility and • Kidney and
• Brain functions.
• Are aggravated by environ-
mental factors [like obesity &
lack of physical activity].
34
P-A M-3 L-3 Pancreas
• The pancreas consists of exocrine (80%) and endocrine portions (2%); rest is formed
by ducts, blood vessels and connective tissue.
• Human pancreas contains 1-2 million islets of Langerhans. These are scattered
throughout the pancreas, more plentiful in the tail.
• Each islet consists of at least four types of cells- A (alpha), B (beta), D (delta) and
F (PP) cells.
• Beta cells account for 60-75% of cells of an islet; these are generally located in
the centre.
Islets of Langerhans
Islets of Langerhans Cells of Islets of Langerhans Secretion of cells
• Human pancreas contains 1-2 • These are scattered through- • Alpha cells secrete glucagon
million islets of Langerhans. out the pancreas, more plenti-
ful in the tail. • Beta cells secrete insulin
• These are the endocrine units
of pancreas. • Each islet consists of at • Delta cells secrete soma-
least four types of cells- tostatin
• A (alpha), B (beta), D (delta) • PP cells secrete pancreatic

and F (PP) cells. polypeptide.
• Beta cells account for

60-75% of cells;
• Alpha cells make up about

20% of an islet.
Islets of Langerhans
Islets of Langerhans Pancreas
35
P-A M-3 L-4 Insulin
• Insulin is a hormone synthesized in the beta cells.

• It is first formed as preproinsulin in the rough endoplasmic reticulum.
• It is then cleaved immediately into proinsulin and transported to Golgi apparatus
where packaging into secretory granules takes place.
• Then it is cleaved further into insulin and C-peptide in equimolecular amounts.
Insulin is composed of two peptide chains- A chain of 21 amino acids and B
chain of 30
amino acids connected by two disulfide bridges.
• Insulin has a circulatory half-life of 3-5 minutes.
Insulin synthesis in the beta cells (in 3 steps)

It is first formed as preproinsulin in the
Step 1 Preproinsulin
rough endoplasmic reticulum
It is then cleaved immediately into proinsu-
lin and transported to Golgi apparatus
Step 2 Proinsulin
where packaging into secretory granules
takes place.
During secretion it is cleaved further into
Step 3 insulin and C-peptide in equimolecular Insulin
amounts.
Insulin structure
Insulin hormone Insulin molecule with C-peptide
1. Insulin is composed of two peptide
chains
2. A chain of 21 amino acids and B chain
of 30 amino acids connected by two
disulfide bridges.
3. Insulin has a circulatory half-life of 3-5
minutes.
4. It is catabolized by the liver, kidney
and also placenta.
36
P-A M-3 L-5 Insulin secretion
Blood glucose stimulates beta cells to secrete insulin. Events during the
process are:
1. Blood glucose molecules enter into the beta cell through the Glucose Transporter-2
(GLUT2) of cell membrane. Glucose does not require insulin here
(This cell is an insulin independent cell).
2. Within the cell, ATP/ADP ratio goes up due to increased production of ATP
from glycolysis.
3. ATP sensitive potassium channels get blocked.
4. Membrane becomes depolarized.
5. Voltage-gated calcium channels get opened.
6. Entry of calcium within beta cell.
7. Insulin is released by exocytosis.
Insulin secretion by blood Glucose
3 steps
glucose GLUT2 ATP-sensitive

uptake potassium
channel
voltage-gated
calcium channel
storage granules
Step 1. Glucose entry to beta cell

Beta cell is an insulin independent cell and blood glucose molecules enter into the cell
through the Glucose Transporter-2 (GLUT2) of cell membrane.
Step 2. Depolarization of beta cell membrane
Within the cell, ATP/ADP ratio goes up due to increased production of ATP from glycol-
ysis. ATP sensitive potassium channels get blocked.
Membrane becomes depolarized.
Step 3. Insulin release
Voltage-gated calcium channels get opened. Entry of calcium within beta cell. Insulin is
released by exocytosis.
37
P-A M-3 L-6 Tissue & insulin action
Our body cells/tissues can be divided in to 2 groups on the basis of their dependency
on insulin for uptake of blood glucose: Insulin dependent and Insulin independent.
Skeletal
Brain cells
muscle cells
Gut epithelium Smooth muscle cells
Cells of nephron Cardiac muscle cells
Red blood cells Liver cells
Beta cells of Fat cells

pancreas
Blood glucose can enter into the cell Blood glucose cannot enter into the cell
without help of insulin without help of insulin
Insulin action at tissue level

Tissue: Liver Tissue: Fat Tissue: Skeletal muscle
• Increased protein synthesis • Increased glucose entry • Increased glucose entry
• Increased lipid synthesis • Increased fatty acid • Increased glycogen
• Decreased glucose output synthesis synthesis
• (due to decreased glucone- • Increased triglyceride • Increased protein synthesis
ogenesis, increased glycogen deposition • Decreased protein c
synthesis & increased glycoly- • Activation of lipoprotein atabolism
sis). lipase • Decreased release of
• Inhibition of hormone-sen- gluconeogenic amino acids
sitive lipase
38
P-A M-3 L-7 Insulin secretion in healthy subjects
Blood glucose is the principal stimulator of beta cells of the pancreas to

secrete insulin
• There is a continuous low-level secretion of insulin (approximately 1 unit per hour)
between meals and throughout night. It is called ‘basal insulin’. So about 24 units
of insulin is secreted as basal secretion.
• Following meals there is sharp rise, which is called ‘prandial or bolus insulin’
release. The rate and amount of secretion is influenced by the amount and
composition of meals. On an average there is also another 24 units of insulin
secretion per day as meal related bolus.
• A bolus release shows two phases: 1st phase is sharp and transient rise lasting
for less than 10 minutes; this is followed by 2nd phase that is sustained and
persists till the blood glucose goes back near to the basal state.
Blood glucose and insulin throughout the day
Basal insulin release

There is a continuous low-level secretion of insulin (approximately 1 unit per hour)
between meals and throughout night. It is called ‘basal insulin’. So about 24 units of
insulin is secreted as basal secretion.
Prandial or bolus insulin release
Following meals there is sharp rise, which is called ‘prandial or bolus insulin’ release.
The rate and amount of secretion is influenced by the amount and composition of
meas. On an average there is also another 24 units of insulin secretion per day as meal
related bolus.
Phases of bolus insulin release
A bolus release shows two phases: 1st phase is sharp and transient rise lasting for
less than 10 minutes; this is followed by 2nd phase that is sustained and persists till
the blood glucose goes back near to the basal state.
39
Glucose homeostasis during fasting state in healthy
P-A M-3 L-8
subject
Glucose homeostasis during fasting state

• When there is no glucose supply to blood from the gut such as during night and
between meals, our body mechanism is adjusted to ensure glucose supply to the
vital tissues.
• This adjustment takes place by the three processes
• insulin secretion goes down,
• hepatic glucose output (HGO) increases and
• glucose uptake predominantly by insulin independent cells (vital tissues of brain,
heart, kidney)
Blood glucose during fasting state
Three adjustment processes during fasting state
Glucose utilization during fasting state
Fasting state Events to adjust

In between meals and throughout night, Insulin secretion goes down (1)
when there is no glucose supply to blood
from the gut, our body mechanism is IIncreased hepatic glucose output (2)
adjusted to ensure glucose supply to the
Glucose uptake by insulin independent
vital tissues by the three processes: cells (3)
40
Glucose utilization during fasting state
Following an overnight fast, the majority 1. Insulin-independent tissues - the brain
(~75%) of glucose disposal occurs in and splanchnic organs utilize ~50% and
insulin independent tissues. ~25% respectively;
2. Insulin-dependent tissues- primarily

muscle utilizes only 25% .
Basal glucose utilization (~2 mg/kg/min)
is precisely matched by glucose production
by liver.
Glucose homeostasis after food intake in healthy

P-A M-3 L-9
subjects
Glucose homeostasis after food intake
Following ingestion of meal, when there is excess glucose supply to blood from the gut,
our body mechanism is adjusted to ensure euglycemia by the following processes and
effects:
• Three adjustment processes: a) Insulin secretion increases; b) Suppression of
hepatic glucose output (HGO) and c) Glucose uptake by insulin dependent cells
(muscle, fat).
• Two effects of hyperglycemia following meal: a) Enhanced muscle glucose uptake

(mass effect) and b) Suppressed hepatic glucose output.
Glucose after food intake
41
Postprandial state Events to adjust
Following ingestion of meal, when there is Insulin secretion increases (1)
excess glucose supply to blood from the
gut, our body mechanism is adjusted to IIncreased hepatic glucose output (2)
ensure euglycemia by three processes.
Glucose uptake by insulin independent
cells (3)
The hyperglycemia induced following meal per se can independently
enhance muscle glucose uptake (mass effect) and
suppress of hepatic glucose output (HGO).
Glucose homeostasis during fasting state in healthy

P-A M-3 L-10
subject
• Different pathophysiological mechanisms of different types of diabetes

result in ‘Hyperglycemia’ and it is the biochemical hallmark of DM.
• Environmental factors trigger the diabetogenic process in a genetically
susceptible individual.
• Impaired beta cell function (insulin deficiency) and/or inefficient action
(insulin resistance) are the central mechanisms of hyperglycemia
• The complications in diabetic state are most likely secondary to
hyperglycemia.
Pathophysiology
Hyperglycemia Mechanisms of hyperglycemia Mechanisms of complication
Hyperglycemia, the Environmental factors The complications in diabet-
biochemical hallmark of trigger the diabetogenic ic state are most likely
diabetes mellitus, is the process in a genetically secondary to hyperglyce-
reflection of different patho- susceptible individual. mia.
physiological mechanisms Impaired beta cell function
playing differently in differ- (insulin deficiency) and/or
ent classes of diabetes. inefficient action (insulin
resistance) are the central
mechanisms of hyperglyce-
mia.
42
Pathway to development of DM
P-A M-3 L-11 Risk factors of diabetes
Risk Factors (RF) are of two types: Modifable and Non-modifable

Risk factors for T1DM
Modifiable Non-modifiable
• Immunological, viruses • Genetics
• Dietary- cow milk, smoked & cured
meat, coffee, gluten etc.
• Stress
Risk Factors (RF) are of two types: Modifable and Non-modifable

Risk factors for T2DM
Modifiable Non-modifiable
• Over-weight/obesity • Genetics
• Physical inactivity • Aging
• Pregnancy
• Intra-uterine & early childhoodmalnutrition
• Stress
• Smoking
43
P-A M-3 L-12 Pathogenesis of Type 1 DM
Pathogenesis of Type 1 DM
Key defects:
• Absolute insulin deficiency is the main defect.
• Hyperglycemia starts abruptly.
• If not treated with insulin, an acute complication like DKA costs the life within a
short period
Insulin deficiency and ‘Honeymoon’ phase
• The insulin deficiency is present at the time of clinical onset of the disease and
throughout the entire course.
• Though some residual beta cell function may be seen and transient periods of
remission can occur producing the so-called ‘Honeymoon’ phase of the disease.
Genetic and environmental factors
• The decrease in insulin secretory capacity is due to actual loss of beta cell mass.
• An immunological mechanism of beta cell destruction is initiated and maintained
by interplay of genetic and environmental factors.
Genetic influence
• The precise nature of the genetic influence in the pathogenesis of T1DM is still
unclear.
• Monozygotic twins have a 20-50% concordance for T1DM.
• The risk for siblings of diabetic patients is 6-10%.
• The offsprings of women with T1DM have a lower risk of disease (2.1%) than
off springs of men with T1DM (6.1%).
HLA linkage
• HLA DR3 and DR4 are associated with 3-5 folds increase in risk for T1DM.
• HLA B8 and B15 also show similar associations.
• Increasingly HLA B8/DR3 are associated with a persistence of islet cell antibodies
(ICA), whereas HLA B15/DR 4 are associated with development of high titer of
insulin auto-antibodies (IAA).
44
Parthenogenesis of T1DM
Factors interplaying Natural history
P-A M-3 L-13 Pathogenesis of Type 2 DM
Key points
• T2DM is heterogenous disorder.

• Hyperglycemia is not only result of defective insulin action (sensitivity) but also
contributed by progressive beta cell destruction leading to diminishing insulin release.
• The impact of the two defects - sensitivity and release of insulin - varies from person
to person and in same person from time to time. One group of patients may exhibit
severe impairment of insulin release and normal sensitivity. Another group of patients
demonstrate exaggerated insulin release, mostly in the early phase of the disease.
• T2DM is polygenic disorder. The exact interaction of genetics and environment during
its development is unclear
• Monozygotic twins have a 60-90% concordance for T2DM.
• The risk for T2DM in siblings of diabetic patients is 10-33%. Connubial has more
chance of T2DM than an offspring of single parent with diabetes.
• Offsprings of women with T2DM have 2-3 folds greater risk of developing diabetes
than do offsprings of men with the disease
Natural history of T2DM
• It starts by breakdown of healthy status of a genetically susceptible individual.

• Earliest abnormality is insulin resistance without any glucose-intolerance.
• Glucose intolerance begins with the appearance of IFG or IGT.
• Ultimately it reaches DM level with increasing glucose intolerance.
45
Parthenogenesis of T2DM
Factors interplaying in T2DM Natural history
P-A M-3 L-14 Insulin release in T2DM
Basal insulin secretion

• In early stage the basal insulin secretion is usually normal in non-obese and high
in obese type 2 DM patients.
• In late cases due to progressive failure of beta cells the basal insulin secretion
becomes low or low normal.
Post meal insulin secretion

• 1st phase is absent from very early stage (before the pre-diabetic stage).
• 2nd phase may be high or normal in early stage but become low later.
Insulin release in T2DM

Basal insulin secretion Post meal insulin secretion Phases of insulin release
• In early stage the basal • There is impairment of • The first phase of insulin
insulin secretion is usually the capacity of beta cells to release is lost/suppressed
normal in non-obese and release insulin when stimu- and the second phase may
high in obese patients. lated by glucose or carbohy- be low, normal or high.
drate-rich meal in type 2
• In late cases due to diabetes.
progressive failure of beta
cells the basal insulin
secretion becomes low or
low normal.
46
P-A M-3 L-15 Beta cell failure
Progressive beta cell failure

• Progressive beta cell failure starts as a very early process of diabetogenesis of
T2DM and is much advanced by the time hyperglycemia starts.
Progressive failure
• As individuals progress from normal glucose tolerance to IFG state, there is a 50%
decline in beta cell mass.
• A person in IGT state have already lost over 80% of their beta cell function.
• So, a significant loss of cell mass and function long before the onset of T2DM.
Important causes of beta cell failure
• Advancing age
• Genetic factors
• Insulin resistance - causes beta cell failure by continuous hyper secretion of
insulin and amyloid polypeptide, and direct beta cell impairment
• Glucotoxicity - chronically elevated glucose level impairs beta cell function
• Lipotoxicity - elevated plasma free fatty acid (FFA) level and deposition of fat in
the beta cell impair insulin secretion
• GLP-1 deficiency
47
P-A M-3 L-16 Insulin resistance & Metabolic syndrome
Insulin resistance (IR) and T2DM

• IR is also an early finding in type 2 DM especially in obese and some non-obese
patients.
• It may exist many years prior to the onset of diabetes.
• The molecular basis of the resistance seems to reside both at the receptor as well
as post-receptor levels.
Observations provide ample evidence to support this in T2DM

• higher basal insulin level,
• low glucose-insulin ratio,
• decreased effect of exogenous insulin,
• glucose clamp with insulin infusion study etc.
48
Insulin resistance — impact in diabetogenesis
• The rate of basal hepatic • IR at muscle accounts • IR causes increased
glucose production (HGP) for over 85-90% of the lipolysis leading to high
is increased by an increase impairment in total body plasma FFA concentration,
in hepatic gluconeogenesis glucose disposal in T2DM which induces hepat-
due to hepatic insulin subjects. It results in a ic/muscle insulin resis-
resistance, increased large increase in blood tance and impairs insulin
circulating glucagon level glucose. secretion.
and activity.
• Glucotoxicity and lipotox- • Dysfunctional fat cells
• Glucotoxicity and lipotoxicity are also important. produce excessive amount
icity also play important of insulin resistance-induc-
role here. ing adipocytokines.
• Enlarged fat cells are

insulin resistant, and have
diminished capacity to
store fat.
Insulin resistance: causal factors and effects

Causal: Genetic, Aging, Medication, Obesity, Inactivity, Rare conditions
Effects: Type 2 DM, Hypertension, Dyslipidemia,
49
Metabolic syndrome (MS)
Metabolic syndrome (MS) is associated with increased insulin resistance
and plays key role in development of many NCDs including T2DM.
• A waist circumference more than normal represents insulin resistance and
regarded as the most important component of the syndrome.
• MS is diagnosed by three or more features from 5 features, namely a) central
obesity by waist circumference. b) high blood pressure, c) dyslipidemia
(high TG & low HDL Cholesterol) and d) raised fasting blood glucose.
MS is the combination of three or more of the 5 features

(IDF criteria: No. 1 plus any two from No. 2-5)
No. Parameter Value
• >90 cm (in male) and
1. Waist circumference
• >80 cm (in female)
2. Blood pressure • >130/85 mm of Hg
• <40 mg/dl (in male) and

3. HDL cholesterol
• <50mg/ dl (in female)
4. TG • >150 mg/ dl
5. Fasting blood glucose • >5.6 mmol/L
50
P-A M-3 L-17 Incretin, Glucagon, SGLT-2, Brain factors and T2DM
Beyond Insulin
In addition to beta cell and its insulin other factors play important roles in
the development of T2DM are
• alteration of incretins of gastrointestinal tract,
• hyperglucagonemia by alfa cells of pancreas,
• increased glucose reabsorption by SGLT-2 (sodium glucose cotransporter-2) in the
kidney, and
• hypothalamic factors of brain.
Incretins: GLP-1 and GIP

Two incretin hormones contribute in development of T2DM.
• GLP-1 (glucagon like peptide-1) and
• GIP (glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide).
GL P-1 is secreted by L-cells of distal intestine and GIP is secreted by K-cells of
proximal intestine.
The progressive beta cell failure is linked with incretin abnormality since its early
stage of diabetes. In T2DM there is deficiency of GLP-1.
Glucagon
• Glucagon level is elevated in T2DM patients and it contributes to raised hepatic

glucose output (HGO) and is responsible for raised fasting blood glucose.
• In T2DM liver tissue is hypersensitive to glucagon and therefore there is increased
gluconeogenesis.
SGLT-2
• Normally the kidneys filter l60gm of glucose every day.

• Ninety percent of the filtered glucose is reabsorbed by SGLT2 (sodium glucose
cotransporter) in the convoluted segment of the proximal tubule, and the rest is
reabsorbed by the SGLT1 in the straight segment of the descending proximal tubule.
• In diabetes the renal tubular reabsorptive capacity for glucose by SGLT2 is increased.
51
Brain factors
• Normally after food intake appetite is suppressed by raised insulin.
• But in obese subjects appetite does not go down despite hyperinsulinemia leading
to worsening obesity and glucose intolerance.
• It is very much clear that the current epidemic of diabetes is being driven by obesity.
• In the hypothalamic key centers for appetite regulation, the inhibitory response
following food ingestion is reduced in obese, insulin-resistant subjects. The brain,
like other organs (liver, muscle and fat), may be resistant to insulin.
There are 16 study Lessons in Module 3. I understand the following points.
In healthy people blood glucose is maintained within a range by insulin actions; and
secretion of insulin is regulated by blood glucose.
In DM insulin actions and insulin secretion are impaired; total beta cell failure is seen
in T1DM from beginning while in other classes it occurs progressively.
In addition to abnormalities of insulin - a. glucagon, b. incretins, c. kidney and d. brain

functions contribute to T2DM development.
There are risk factors of DM development - some of them are modifiable. So there is
scope of prevention also.
Further reading
1. Text Book of Diabetes, 4th edition, edited by Richard I G Holt, Clive S Cockram, Allan
2. Davidson's Diabetes Mellitus -Diagnosis & Treatment, 5th edition, edited by A P
Hamel & R Mathur, Saunders, 2004.
3. Clinical Diabetes - Translating Research into Practice, 1st edition, V A Fonseca,
Saunders, 2006.
4. From the Triumvirate to the Ominous Octet: A new Paradigm for the Treatment of
Type 2 Diabetes Mellitus, Ralph A DeFronzo, Diabetes, 2009.
52
Phase-B
Module-4: General Principles in Management of DM

Module-5: Drug Therapy in Diabetes Mellitus
Module-6: Acute Complications of Diabetes
Mellitus
Module-7: Microvascular Complications of
Diabetes Mellitus
53
Module-4
General Principles in Management

of DM
54
P-B M-4 L-1 Objective
Objective
• To know the general principles of management of diabetesmellitus.
• To discuss/learn the issues regarding adjustment of one’s/ individual daily life by
setting specific targets that will enable living healthy in spite of diabetes.
• To acquire the skill on self monitoring of blood glucose (SMBG), urinary glucose,
protein and ketone body tests, etc.
• To discuss/learn the basic principles of dietary modification in diabetes and to teach
healthyeating.
• To make/ advice recommendations for intensity, duration and frequency of exercise
for individualpatient.
P-B M-4 L-2 General Principles in Management of DM
Management of diabetes mellitus, till date, in general aimed at supporting

people to live with minimum or no risk of complication(s).
• This is achievable through some specific goals of blood glucose, blood pressure,
lipids, body weightetc.
• The specific or set goals are termed as targets. "Treat to target" is the principle of
management ofDM.
• There are algorithms for initiation, maintenance and switching over to other regimen
for Treat toTargets.
55
Key points
• Diabetes mellitus is a life-long disorder. Diabetic Education (DE) is an important
component todevelop knowledge, skill and attitude of patient and family to take part
inmanagement.
• T1DM is a deficiency disorder from the onset and its management is ‘efficient
replacement of the deficiency,’ and lifestyle is to be synchronized with insulin
administration.
• T2DM is a more complex disorder, and here lifestyle modifications/interventions
have the potentiality to correct some of factors which are not only proven as risk
factors for developing diabetes but also responsible for deterioration in glycemic
status and development of other co-morbidities e.g. hypertension, cardiovascular
diseases, dyslipidemia etc.
• A significant portion/numberof these T2DM patients can achieve and maintain the
goals set for management with only lifestyle measures for a reasonable period
(if diagnosed early). Drug therapy is added along with the lifestyle changes when the
treatment target falls below that is to be achieved, or when there is compelling
reason. The lifestyle modification becomes more important as because that needs
to be synchronized withdrug.
Key points
General Treatment Components of Diabetes mellitus
DiabetesMellitus E
D
U
C
MNT A
Exercise Monitoring T
Medication I
O
N
Target
N.B: MNT - Medical Nutrition Therapy
56
P-B M-4 L-3 Aims and steps of Treatment of DM
Aims and steps of treatment of DM are shown in tables below
Aims of treatment of DM
1 To make the patient symptom-free
2 To maintain (near) normal blood glucose level round the clock or most of the
time of the day
To prevent acute metabolic derangement, such as hypoglycemia, ketoacidosis,
3
HHS etc
4 To prevent or delay chronic complications of diabetes, such as nephropathy,
retinopathy, neuropathy etc
To ensure proper growth and development of children or young subjects
5
To maintain health of pregnant and lactating mothers
6
To support a productive and socially respectful life
7
Steps of management of DM
Steps
1 Confirmation of diagnosis
2 Analysis of factors to initiate treatment
Targets of treatment (glycemic & nonglycemic)

3
4 TSelection & initiation of a treatment regimen
Monitoring & changing treatment regimen

5
Screening for complications & referral
6
Evaluation
7
57
P-B M-4 L-4 Step 1. Diagnosis and 2. Factor Analysis
Step 1 and Step 2 of treatment of DM are shown tables below
Step 1. Confirmation of Diagnosis by Test

Tests for confirmation of diagnosis
Other tests: FBG only, HbA1c, RBS can
also be done.
See details in Module 2
Step 2. Analysis of Factors

Factors
(patient factors may influence the choice of
initial treatment regimen)
• Age of theperson
Type of DM
1 • Bodyweight
• Acute/chronic complications/illnesses, pregnan-

cy/lactation, major surgeryetc.
2 Associated conditions
• Lifestyle of the person
• Degree ofhyperglycemia
• Previous anti-diabetic agents (if any)

3 History
• Socio-economiccondition
58
P-B M-4 L-5 Step 3. Targets of Treatment
Treat to targets is the most important agenda in management of DM.

Treatment targets of DM are glycemic, lipid and others as follows:
Blood (plasma) glucose (For adult)

Parameter Target
1 Fasting /pre-meals < 6.0 mmol/L
2 Non-Fasting/post meals? < 8.0 mmol/L
3 HbA1c < 7.0 %
Blood Lipids
Parameter Target
1 LDL cholesterol < 100 mg/dl
2 HDL cholesterol > 40 mg/dl (male) & > 50 mg/dl (female)
3 Triglyceride < 150mg/dl
Other Targets
Parameter Target
Systolic < 140 mm of Hg & Diastolic < 80
1 Blood Pressure
mm of Hg.
BMI < 25kg/M2 & Waist circumference
2 Body weight
(WC) < 90 cm (male) < 80 cm (female)
Teaching, training & empowerment to take
3 Diabetic Education
part in treatment
59
P-B M-4 L-6 Step 4: Selection & Initiation of a Treatment Regimen
Key points on selection of regimen for treatment at diagnosis

• Severity of Glucose Intolerance is the primary determinant of initial treatment regi
men in T2DM.
• Insulin is the single treatment option in T1DM
• In GDM if lifestyle fails to achieve the glycemic target only insulin is added.
• Principles of T2DM is mostly followed in other type of DM.
Type Lifestyle based Secretagogue based Insulin based
Consist of lifestyle + Insulin Insulin secretagogue Insulin with lifestyle

sensitizer with lifestyle + + Insulin
Insulin
(+ other)* sensitizer (+ other) sensitizer (+ other)
Used in T2DM & GDM T2DM All types of DM
Termed Regimen A Regimen B Regimen C
*Thiazolidinedione, alpha-glucosidase inhibitor, DPP-4 inhibitor, GLP-1 agonist, amylin

analogue, SGLT2 inhibitors etc
Which regimen to choose to start treatment of Type 2 DM?
Lifestyle based Secretagogue based Insulin based
• Lifestyle+ Insulin • Insulin secretagogue • Insulin with Lifestyle+

sensitizer (+ other) with Lifestyle+ Insulin Insulin
• sensitizer (+ other) • sensitizer (+ other)
• HbA1c <8% • HbA1c 8 –<10 % • HbA1c > 10%
• (FBG <11.1 mmol/L) • (FBG 11.1 -<16.7 • (FBG >16.7 mmol/L)

mmol/L)
When there is contraindica-

tion of secretagogue regime
A or C can be used
60
P-B M-4 L-7 Step 5: Monitoring & Changing Treatment Regimen
Monitoring of DM
Glucometer and SMBG Laboratory test HbA1c
Blood Glucose test is done If all these facilities are HbA1c should be tested at
by glucometer covering unavailable, blood glucose diagnosis and during follow
pre-meal, post-meal and measurement at laboratory up of DM because it helps
critical periods in persons. can be done in selection / change of a
therapeutic regimen.
Structured different pre-and post-meal blood glucose testing should be

done so that it helps in decision making in treatment. See some examples
below:
SMBG of an Adult with Type 2 DM
• All values (pre & post meals) are withintargets.

• Existing treatment is continued
• Provided any drug(s) of the regimen do not have any limitation inuse.
61
• All values (pre & post meals) are higher than targets but post meals are not higher
than pre meal(<+4mmol/L)
• Treatment priority will be to bring fasting blood glucose totarget
• It is done by adding or increasing dose of long acting secretagogues /insulin.
• Fluctuating or Erratic values.

• Priority will be to look into lifestyle (meals, physical activitiesetc).
• Education (Diabetic Education) is to be strengthened in addition to
treatmentregimen.
Which regimen to choose to start treatment of Type 2 DM?
Lifestyle based Secretagogue based Insulin based
Lifestyle ± Metformin Lifestyle ± Secretagogue ± Lifestyle ± Insulin ±

(± Others) Metformin ± Others Metformin ± Others
Continue Regimen A Continue Regimen B Continue Regimen C

• so long HbA1c < 7% • so long HbA1c < 7% • maintain HbA1c withintar-
(forAdult) (forAdult) get
• if not go to Regimen B • or no contraindication of
Secretagogue
• if not go to Regimen C
62
Step 6: Complications Screening, Referral &
P-B M-4 L-8 Step 7: Treatment Evaluation
Step 6. There are 2 basic components of diabetes management

Screening and referral
1. Early detection of complication by routine screening.
2. Appropriate referral
Step 7. The whole management strategy should be analyzed and evaluated

from time to time so that the best treatment can be offered.
Evaluation
• Continuous evaluation is an integral step of DM management.
• The whole management strategy should be analyzed and evaluated from time to
time
P-B M-4 L-9 Lifestyle Modification in DM
The important issues of lifestyle of diabetics (also prediabetics):

• Appropriate lifestyle of diabetics include their dietary habit, physical activity and
exercise, regular monitoring of blood glucose, physical care such as foot and oral
care, regular follow up etc.
Lifestyle Management of DM include
Diet Physical activity Monitoring
•Healthy Dietary habit • Regular Physical activity • Regular monitoring of

/exercise blood glucose,
• Physical care such as
foot and oral care,
• Regular follow up etc.
63
P-B M-4 L-10 MNT in DM
MNT
A proper diet is a fundamental element of therapy in all diabetic individuals.
An appropriate dietary management is called Medical Nutrition Therapy (MNT).
Some important terms relevant to MNT

• Diet: A proper diet is a fundamental element of therapy for all diabetic individuals . A
diet recommended for a diabetic patient is, in fact, a ‘balanced diet’ for any one.
• Balanced diet: A balanced meal is a combination of carbohydrates, fats, proteins and

fibres appropriate for the individual; at the same time, it should provide sufficient
vitamins, minerals and micronutrients.
• Dietplan: A diet plan should be individualized according to his/her needs; it must be

simple to understand and easy to follow.
• Dietician: All diabetics should be referred to a dietician for counseling at diagnosis of
diabetes and also subsequently if they have problem with their diet adjustment.
• Special diet: Special counselling is necessary in children and adolescents, pregnant
and lactating women, and other conditions of acute or chronic illnesses where diet is
of immense concern.
Goals of MNT in Diabetes

1. To eat a balanced and regular meal
2. To achieve metabolic goals, e.g. blood glucose, lipid, hypertension etc
3. To attain and maintain desirable body weight.
4. To provide adequate nutrition for health and growth in pregnant and lactating
mothers, and children
5. To prevent/delay complications of diabetes
6. To preserve the pleasure of eating
Goals of MNT in Diabetes

1. Calorie intake
2. Components of nutrients
3. Meal timing and consistency
4. Weight management
64
P-B M-4 L-11 MNT: Calorie Requirement
Calorie requirement of diabetes

The daily calorie requirement is related to existing body weight and activity level but not
on diabetic status. Calorie requirement is similar in diabetics and non-diabetics.
Factors determining calorie requirement

The daily calorie requirement is determined primarily by two factors
a. existing body weightand
b. activity level.
Other factors that have influence on caloric requirements are lifestyle, pregnancy,
lactation, other illnesses, and age, especially in growing period.
Determinant of Daily Calorie allowance

The following formula is used
Daily calorie allowance (Kcal)=Ideal body weight (IBW) X Calorie factor (CF).
• BW is obtained from standard height-weight charts. It can also roughly be
calculated by subtracting 100 from height (in centimetres).
• CF is obtained from a body weight-activity level chart (see below).
Caloric Factor (CF)
Activity Level
Body Weight
Sedentary Moderately Active Active
Over weight 20/25 25/30 30/35
Normal weight 30 35 40
Under weight 35 40 45
65
P-B M-4 L-12 MNT: Component of Nutrients
Components of nutrients
The impact of specific dietary composition on glycemic control and cardiovascular risk
remains uncertain in diabetes
Composition of macronutrient
The optimal macronutrient composition should be individualized depending upon
• weight lossgoal,
• other metabolic needs (e.g. hypertension, dyslipidemia, nephropathy etc.)and
• individual preference.
Table: Distribution of macronutrient

Carbohydrate Fat Protein
50-60% of DCI 30% of DCI 10-20% of DCI
Fibber 20-35 grams (or 14 Saturated fats < 10%
grams 1000/kcal) Trans-fat <1% Cholesterol
< 300 mg
P-B M-4 L-13 MNT: Carbohydrates, Fat & Protein
Carbohydrates, fat & protein intake by diabetic person

Carbohydrates
(Intake of carbohydrates causes sudden rise in blood sugar level. Should be limited
or avoided and Carbohydrates with lower glycemic index and glycemic load are to be selected.)
Limit or avoid Carbohydrates: Select Carbohydrates:

Refined or simple carbohydrates Un-refined complex carbohydrates such
e.g. Sugar, glucose, soft drinks, jam, as bread, cereals, potatoes, rice etc. are
honey, marmalade, sweets, cakes, more suitable, as they are digested more
chocolate etc. cause sudden rise in slowly in the body And causeless rapid
blood sugar level. Intake of these should rise in blood sugar levels. Carbohydrates
be limited. with lower glycaemic index and glycaemic
load are preferred.
66
Fats intake
(Fatty foods have high calorie which lead to weight gain and increase the risk of
cardiovascular disease.)
Fats solid at room temperature are high in saturated fat. It is abundantly present in
cream, cheese, butter, ghee, animal fat, coconut oil, palm oil etc. Rich sources of trans
fat are margarine, French fry, doughnut, pastry, pizza, pie, biscuit/cracker/cookie etc.
Dietary cholesterol is high in egg yolk, butter, ghee etc.
P-B M-4 L-14 MNT: Vitamins, Sweeteners & Alcohol
Vitamin and minaral supplements

• There is no sufficient or clear evidence of benefit from vitamin or mineral
supplementation in diabetes who do not have under lying deficiencies.
• Routine supplementation with antioxidants or micronutrients (e.g. chromium,
magnesium, vitamin D) or other herbs/supplements in diabetes is not recommended.
Alternative sweeteners
• Sweetening agents, which provide sweetness but little calories, are now approved
for use.
• Non-nutritive sweeteners include aspartame, neotame, saccharin, acesulfame and
sucralose. These are preferred in diabetes. Reduced calorie sweeteners include
sorbitol, mannitol etc. All are safe when consumed within acceptable limit.
Alcohol
• Alcohol has various adverse effects in diabetes.
• Daily intake should be limited to one dink (15-gram ethanol) or less in females and
two drinks (30 gram) or less in males.
• Alcohol should be avoided in pregnancy, liver disease, pancreatitis, advanced
neuropathy and severe hypertriglyceridemia.
• Alcohol may cause delayed hypoglycaemia, especially in those using
hypoglycemicagents
67
P-B M-4 L-15 MNT: Weight Management
As most of the people with type2 diabetes and prediabetes are over-weight or
obese, an important aim of MNT in this group is to achieve body weight goals.
This can be achieved by calorie allowance as stated earlier.
Caloric restriction and Increase in physical activity are the main strategies of
weight loss.
Caloric restriction
• A moderate caloric restriction (250-500 calories less than average daily intake as
calculated from food history) can be done.
• A hypo-caloric diet, irrespective of weight loss, is associated with increased
sensitivity to insulin and improvement in blood glucose level. Moderate sustained
weight loss (5-10%, or 2-8 kg), irrespective of initial weight, in overweight/ obese
individuals can have a lasting benefit on blood glucose, dyslipidemia and
hypertension.
Increase in physical activity

• The dietary practice must be supported by an increase in physical activity
Benefits of weight loss in overweight/obese

• Decrease in mortality
• Normalization of blood glucose
• Maintenance of blood pressure at normal level
• Improvement in blood lipids (all components)
• Fall in cancer-death
68
P-B M-4 L-16 Meal Timing, Composition and Planning
The diet remains a big problem in diabetes care. One of the main reasons for
this is lack of nutritional self-management training. Depending on the individu-
al patient’s learning capabilities, clinical needs, level of motivation and
lifestyle, different methods of teaching can be used:
Meal timing
Consistency with meal timing and day-to-day carbohydrate intake is very important,
specially in those treated with anti-diabetic medications, to avoid erratic blood glucose.
• A meal plan should be based on the individual’s usual food in take, integrating with
lifestylepattern,activitylevel,drugs(ifused)andbloodglucoseresults
Calorie distribution in meals
69
P-B M-4 L-17 Anthropometric Measurement
Body Mass Index (BMI) and Waist Circumference (WC) are 2 important mea-
surements of overweight and obesity. Overweight/Obesity is a risk of diabetes
and other non-communicable diseases like hypertension, dyslipidaemia,
ischemic heart disease, chronic respiratory disease and certain cancers.
Correction of BMI and WC are incorporated as targets of treatment of T2DM
Weight and height measurements are required to determine BMI. The

formula for calculation is as follows:
BMI = Weight in Kg/Height in Meter
BMI helps to diagnose and grade obesity using standard norm gram
Category
<18.5 Underweight
18.5 - 24.9 Normal
25 - 29.9 Overweight
30 - 39.9 Obese
>40 Morbid Obese
Waist circumference
Waist circumference (WC) is a measure of central adiposity. Central adiposity rather
than total adiposity is more related to cardio-metabolic risk. Adiposity is referred as
‘pear’ or ‘apple’ shaped. A person with pear shape have a higher WC and so greater risk
of cardiovascular complications than apple shaped (higher gluteal fat) person
Desirable Waist Circumference:
for male <90 cm and
for female <80 cm
Hip Circumference (HC) and WC are used to calculate a parameter called 'Waist-Hip
Ratio’ (WHR) or abdomino-gluteal ratio. The formula to have WHR is asfollows:
WHR= WC (in cm)/HC (in cm)
WHR is considered risky for developing cardiovascular and metabolic diseases if >0.9
for male and if >0.8 for female
70
Waist or abdominal circumference is a Hip or gluteal circumference is taken at
measure at midway between the costal the largest circumference at the posterior
margin and the iliac crest; it is the extension of the buttocks, measured over
smallest circumference at the waist the greater trochanters
P-B M-4 L-18 Exercise and DM
Exercise
Exercise is an important component of treatment of diabetes mellitus. In addition to
physical fitness exercise helps in preventing atherosclerosis and thereby macroangio-
pathic complications in diabetes. It also improves mental well-being and quality of life.
An exercise plan should be individualized according to his/her physical status, meals,
drugs, profession, interest etc. To start with exercise one should be gradual in increas-
ing the duration and intensity. For adults over the age of 18 years there should be
ultimate target of doing aerobic exercise of moderate intensity for at least 150 minutes
per week or vigorous intensity for at least 75 minutes per week, or equivalent combina-
tion of both types, spread over at least 3 days per week, with no more than 2 consecu-
tive days without exercise. T2DM should perform anaerobic exercise involving all major
muscle groups at least 2 days a week.
Intensity of exercise
Intensity of exercise is assessed by the Maximum Heart Rate (MHR). Formula for MHR
is as follows.
MHR = 220 - Age.
Intensity of exercise is called
a. Vigorous if Heart Rate achieved is > 70% of MHR ; b. Moderate if Heart Rate
achieved is 50 - 70% of MHR; c. Low if Heart Rate achieved is < 50%
71
Prior to recommending any exercise programme one should be careful of
a) Coronary HeartDisease,
b) proliferativeretinopathy,
c) neuropathy, advance renalfailure,
d) hypoglycemia unawareness,etc.
Exercise: Aerobic and Anaerobic
Exercise: Aerobic
• Aerobic exercise uses large group of muscles, can be maintained continuously, and
isrhythmic in nature.
• This type of exercise overloads the heart and require oxygen to provideenergy.
• Examples- Walking, running, treadmill, stair climbing, cycling, aerobic dancing,
swimming, joggingetc.
Benefit of aerobic exercise

• Increases maximal oxygen consumption
• Improves cardiovascular and respiratory function
• Increases blood supply of muscles and ability to use oxygen
• Lowers resting systolic and diastolic blood pressure in people with hypertension
• Increases HDL Cholesterol and reduces LDL Cholesterol & Triglyceride
• Reduces body fat and improves weight control
• Improves glucose intolerance and reduces insulin resistance
72
Exercise: Anaerobic
• Anaerobic exercise is of short duration.
• This type of exercise can be supported byenergy stored in the muscles and dose nor
require oxygen.
• Examples- Weight lifting, strength training, sprinting at very fast speed etc.
Benefit of anaerobic exercise

• Increase muscular strength
• Improves flexibility of joints
• Reduces body fat and improves lean body mass (musclemass)
• Improves glucose intolerance and reduces insulin resistance
• Improves strength, balance and functional ability in older adults
P-B M-4 L-19 Exercise
Practical points on Exercise
Exercise recommendations for a person with diabetes are same as for a non
1
diabetic.
Exercise program includes a proper warm-up and cool-down periods.
Warm-up should consist of 5 - 10 minutes of aerobic activity (e.g. walking) at
allowed intensity level; it prepares heart for exercise.
After a short warm-up, muscles should be gently stretched for another 5 - 10
2 minutes; it prepares muscles for exercise without injury. This period is called
' stretching period'.
The cool-down period also consists of 5 - 10 minutes of aerobic activity at a
low intensity level after main activity session. It gradually brings heart rate
down to pre-exercise level.
Person with T1DM who do not have any complications and satisfactory
blood glucose profile can do all levels of exercise, including leisure activities,
3 recreational sports and competitive professional performances. The empha-
sis must be given on adjusting therapeutic regimen with level of exercise
and diet and avoiding hypoglycaemia.
In children, extra attention needs to be paid to balance glycaemic control

4 with activity level and for this the support of parents, teachers and trainers
may be necessary. Their meal and activity in school are impertinent.
73
Person with T2DM must view exercise as a vital component for manage-
ment. Exercise along
with a reduced calorie intake may enhance weight loss. Combination of diet,
5
exercise and behavioral modifications is the most effective approach to
weight control. Normally low to moderate intensity long duration exercise is
recommended for weight loss.
The diabetic patient with peripheral neuropathy and loss of protective sensa-
tion should not engage in repetitive weight bearing exercise eg. prolonged
6 walking, treadmill, jogging etc. as these activities may result in blistering,
ulceration and fracture. Non-weight-bearing exercise, eg. swimming, cycling,
rowing, chair exercise, arm exercise, yoga etc. may be better
Person with severe Charcot's joint should avoid weight-bearing exercise, as it

7 can result in multiple fracture and dislocation of ankles and feet even with-
out patient being aware of it.
In patients who have proliferative and moderate to severe non-proliferative
diabetic retinopathy, strenuous activity may precipitate vitreous hemorrhage
or fractional retinal detachment. These individuals should avoid anaerobic
8 exercise and physical activities that involves straining, jarring or Valsalva
maneuvers eg. weight lifting, boxing, heavy competitive sports etc. These
persons may be recommended low impact exercise like swimming (but not
diving), walking or stationary cycling.
Patient with stable coronary heart disease should perform exercise of mod-
9 erate intensity. Person with uncontrolled hypertension should withhold
exercise until control of blood pressure.
If a person develops symptomatic hypoglycemia or ketosis, exercise should
10 be postponed. If blood glucose goes below 5.5 mmol/L the person should
take extra 15 - 30 grams of carbohydrate before exercise.
One should not do exercise during any significant acute illness or uncom-
11
pensated major chronic illness.
During pregnancy moderate exercise eg. walking at moderate speed for 30
12 minutes a day at a time or in divided fashion is advised. Vigorous exercise or
exercises causing pressure in the abdomen should be avoided.
74
P-B M-4 L-20 Summary
There are 18 sections in module 4. I understand the following points.

• Management of DM is aimed at supporting people to live with minimum or no risk
of complication(s).
• There is treatment goals/targets of blood glucose, BP, lipids, body weight etc
• "Treat to target" is the principle of management of DM. There are algorithms for
initiation, maintenance and switching over to other regimen.
• Lifestyle- which includes dietary habit, physical activity and exercise, regular
monitoring of blood glucose, physical care such as foot and oral care, regular
follow-up etc. - is an essential component of DM management.
Further Reading
1. Text Book of Diabetes, 4th edition, edited by Richard I G Holt, Clive S Cockram,
Allan Flyvbjerg & Barry J Goldstein, Wiley-Blackwell, 2010.
2. Davidson's Diabetes Mellitus -Diagnosis &Treatment, 5th edition, edited by A P
Hamel & R Mathur, Saunders, 2004.
Saunders, 2006.
4. Clinical Practice Recommendations, ADA (American Diabetic Association), 2014.
5. Global Guideline for Type 2 Diabetes, Clinical Guidelines Taskforce, IDF
(International Diabetes Federation),2012.
6. Comprehensive Diabetes Management Algorithm, AACE (American Association of
Clinical Endocrinologist) Task Force, 2013.
7. Patient's Guide Book, Diabetic Association of Bangladesh.
75
Module-5
Drug Therapy in Diabetes Mellitus
76
Objective
• To describe the mechanisms of action and maximum doses of
various anti-diabetic agents.
• To identify appropriate time to commence drug treatment and type
of drug to be used in different clinical situations.
• To identify failure of oral anti-diabetic agents.
• To identify appropriate regimen of insulin to be used in different
clinical situations.
• To provide hands-on training on insulin administration to patients
and their family members.
P-B M-5 L-2 Introduction
• Diabetes mellitus is a serious disorder in respect to its potentiality of

complications alone.
• The availability of insulin and other drugs with different modes of action has
brightened the management of diabetes mellitus.
• Some of these drugs have benefits beyond glycemic control.
• Prevention of complications of diabetes is now more realistic that ever before.
• At the beginning of the 20th century, physicians had no useful weapon against
diabetes.
• Prolonged fasting with rigorous calorie restriction was being practiced in
treatment of diabetes
• before the discovery of insulin. With discovery of insulin and later the oral agents,
treatment of diabetes has become much easier.
Various treatment modes are needed in dealing diabetes, which can be

divided into two:
1. Non-pharmacological (Lifestyle modifications) and
2. Pharmacological (Oral and injectable agents).
Non-pharmacological approach initially can be sufficient for some cases of T2DM;
but all type 1 diabetics and most of the T2DM require pharmacological agents also.
77
Drugs for DM Treatment
Oral anti-diabetic drugs (OADs) Injectable agents
1 Insulin secretagogues 1 Insulin
2 Insulin sensitizers 2 Other agents
3 Alpha-glucosidase inhibitors
4 DPP-4 inhibitors (Gliptin)
5 SGLT-2 inhibitors (Gliflozin)
6 Other agents
P-B M-5 L-3 Oral anti-diabetic drugs (OADs)
• OADs are drugs, which can be administered orally, and help to reduce plasma
glucose concentrations if there is some insulin reserve in the beta cells.
• They are not useful in type 1 diabetes and in those patients with type 2 diabetes
who have advanced beta-cell failure.
• Several oral agents are used in the treatment of diabetes and their number is
increasing day by day.
OAD can be classified on the basis of mechanism of action.
Oral anti-diabetic drugs (OADs)

1 Insulin secretagogues
2 Insulin sensitizers
3 Alpha-glucosidase inhibitors
4 DPP-4 inhibitors (Incretin mimetics - Gliptin)
5 SGLT-2 inhibitors (Gliflozin)
6 Other agents
78
Table showing different classes and sub-classes of OADs (based
on mode of action) used in treatment for T2DM.
OAD Classes Sub-classes OADs Advantages, Hazards & Limitations
Glibenclamide Advantages: Potent drug; reduces

Glipizide premeal and post meal blood
glucose.
Gliclazide
Sulfonylureas Hazards: Hypoglycemia and
Glimepiride weight gain.
Tolbutamide Limitations: Impaired renal and
OAD Classes liver function.
Chlorpropamide
Advantages: Reduces postmeal
Tolbutamide blood glucose only, less hypogly-
Non- Sulfony- cemia.
lureas (Glinide) Hazards: Weight gain.
Chlorpropamide Limitations: Impaired renal and
liver function
Advantages: Improves insulin

sensitivity; reduces premeal
(mostly) and postmeal blood
glucose, favourable effect on lipids
Biguanide Glibenclamide
and NAFLD.
Hazards: GI upset.
Limitations: Impaired renal and
liver function.
Insulin sensitizers
Advantages: Improves insulin
sensitivity; reduces premeal
(mostly) and postmeal blood
glucose, favourable effect on lipids
Thiazolidine-di- (Pioglitazone) and NAFLD.
Pioglitazone Hazards: Weight gain, fluid reten-
ones (Glitazone) tion; raised LDL and IHD (Rosiglita-
zone).
Limitations: Impaired liver function

and heart failure.
79
OAD Classes Sub-classes OADs Advantages, Hazards & Limitations
Advantages: Weight friendly;

Acarbose
reduces postmeal blood glucose.
Alpha-glucosi- Hazards: GI upset.
Miglitol Limitations: Inflammatory bowel
dase inhibitors
disease and malabsorption state;
Voglibose Impaired renal and liver function.
Sitagliptin Advantages: Weight friendly;

reduces premeal and postmeal
Vildagliptin blood glucose.
DPP-4 inhibitors Hazards: GI upset, upper RTI and
Linagliptin pancreatitis.
(Gliptin)
Limitations: Impaired renal func-
Saxagliptin
tion (except Linagliptin)
Alogliptin
Advantages: Weight friendly;

Dapagliflozin
reduces premeal and postmeal
SGLT-2 inhibitors blood glucose.
Canagliflozin Hazards: UTI, genital infection.
(Gliflozin)
Limitations: Impaired renal
Empagliflozin function.
NB: NAFLD - Non Alcoholic Fatty Liver Disease, RTI - Respiratory Tract Infection,
UTI - Urinary Tract Infection. Advantage of one agent over the other and hazard/limitation
80
P-B M-5 L-4 Sulfonylureas and Glinides
1.A. Insulin secretagogues: Sulfonylureas (SU)

• SUs increase the release of insulin from pancreatic beta cells and thus exert a hypo
glycemics effect in diabetic as well as non-diabetic persons. First introduced in 1955,
these are the oldest oral agents and still in use in large scale in type 2 DM.
• Pancreatic action of SU is initiated by binding to a specific sulfonylurea receptor on

the pancreatic beta cells leading to closure of potassium-dependent ATP (K-ATP)
channel. With the closure of K-ATP channel, there is increase in calcium influx and
translocation of secretary granules on the cell surface and extrusion of insulin by
exocytosis.
• Extra pancreatic effect of SU are: a. reduces hepatic glucose output, b. improves

insulin stimulated glucose uptake in muscle, c. stimulates lipogenesis in fatty tissue.
But these effects are not significant.
• Metabolism: SU are rapidly absorbed from gut, have extensive plasma protein
binding and almost completely metabolized by liver, excreted in urine and faeces.
• SU are potent in reducing both pre- and postprandial blood glucose, may cause
hypoglycaemia and weight gain, have limitation of use in impaired renal and liver
function.
• SU are contraindicated in impaired renal and liver function.
81
Table showing duration of action, route of elimination and doses of
different SUs (in secretagogue-based treatment for T2DM)
Dose
Duration Starting Maximum
SUs Elimination adjustment Remark
of action dose dose
interval
Gliben- 24 h Urine & 1.25-2.5 mg 20 mg Every 2
clamide faeces x1; 30 min (in 1-2 weeks
ac doses)
Glipizide 8-12 h Urine 2.5 mg x1; 40 mg Every 2
(~70%) & 30 (in 1-2 weeks
faeces min ac doses)
Gliclazide 8-12 h Urine 40 mg x1; 320 mg Every 2
(~65%) & 30 (in 1-2 weeks
faeces min ac doses)
MR 120 mg
(in 1 dose)
Glimepiride 24 h Urine 1 mg x1 8 mg Every 2
(~60%) & (in 1 dose) weeks
faeces
Tolbut- 6-12 h Urine 100%
amide
Not in use at present
Chlorpropa- 24-72 h Urine >90%
mide
NB: ac - before meal; MR - modified release preparation
82
1.B. Insulin secretagogues: Non-sulfonylureas/Glinides
• Mechanism of action of glinides is similar to the sulfonylureas. But because of their
slightly different binding site, pharmacokinetic profile is also different.
• First introduced in 1983, and is in use in large scale for type 2 DM.
• Hypoglycaemic action is glucose-dependent and hence work better in the presence

of hyperglycaemia and effect wears off as the plasma glucose concentration returns
to the normal range. Therefore these agents are also called ‘prandial glucose
regulator’.
• Metabolism: Glinides are rapidly absorbed from gut, have extensive plasma protein
binding and almost completely metabolized by liver, repaglinide is excreted mostly in
faeces and Nate glinide mostly in urine.
• Glinides are potent in reducing only postprandial blood glucose, cause less hypogly
caemia or weight gain, may be used cautiously in mildly impaired renal and liver
function.
Table showing duration of action, route of elimination and doses of

different Glinides (in secretagogue-based treatment for T2DM)
Dose
Duration Starting Maximum
SUs Elimination adjustment Remark
of action dose dose
interval
Repaglinide 4-5 h Mostly in 0.5 mg x3; 12 mg Every 1-2
faeces 15 min ac (in 3 doses) weeks
(~90%)
Nateglinide 4-5 h Mostly in (60 mg) x3; 360 mg Every 1-2
urine 15 min ac (in 3 doses) weeks
(~80%)
83
P-B M-5 L-5 Metformin & Thiazolidinediones
2.A. Insulin sensitizers: Biguanide/Metformin

• Metformin is the only biguanide now in use to treat T2DM and become a first line
treatment option.
• It has lower risk of hypoglycemia; can be combined with other anti-diabetic drugs
including insulin.
• This do not alter blood glucose levels in non-diabetic persons, but produce
an anti-hyperglycemic effect in persons with diabetes.
• This is well absorbed on oral administration, not bound to plasma proteins,
not metabolized, and are excreted almost unchanged in urine.
• Precise mechanism of action is not clear, but possibilities include: a) inhibition of
hepatic neoglucogenesis; b) increase in insulin sensitivity with peripheral utilization
of glucose; c) delay in absorption of glucose in gut.
• Metformin is started with 500 mg x1 dose during the largest meal daily and then
build up dose weekly. The maximum dose is 2500 mg in 2-3 doses or ER 2000 mg in
single dose. The dose adjustment should be slow e.g. monthly.
• Common side effect of metformin include nausea, vomiting, abdominal pain and
diarrhea.
2.A. Insulin sensitizers: Biguanide/Metformin

• Thiazolidinediones are class of drugs that improve insulin sensitivity and are useful
type 2 diabetes where insulin resistance is a major component in the pathogenesis.
• Mechanism of action of the drug include:
1. Reduces hepatic glucose output and
2. Increases peripheral glucose utilization by improving insulin sensitivity.
• Thiazolidinediones have low risk of hypoglycaemia.
• Pioglitazone is started with 15 mg x1 dose daily and then increase every 4-6 weeks.
The maximum dose is 45 mg in 1 dose.
• Rosiglitazone is started with 4 mg x1 dose daily or 2 mg x1-2 doses daily and then
increase every 4-6 weeks. The maximum dose is 8 mg in 1-2 doses.
• Common side effects of Pioglitazone and Rosiglitazone include weight gain and
fluid retention, and for Rosiglitazone raised LDL and IHD.
84
Table showing initiation and dose titration of insulin sensitizers: Met-
formin and Thiazolidinediones in T2DM
Starting daily
OAD Class Name of OAD Maximum Adjustment
dose
500 mg x1 2500 mg Increase (on the
with meal; build (in 2-3 doses) built-up) by
up the dose ER 2000 mg smallest every 4
weekly (1 dose) weeks.
Biguanide Metformin Reduce dose or
do not initiate - if
eGFR <45;
Stop – if eGFR
<30
15 mg x1 45 mg (in 1dose) Increase by
Pioglitazone smallest every
Thiazolidine-
diones 4-6 weeks.
4 mg x1 or 2 mg 8 mg
Rosiglitazone x1-2 (in 1-2 doses)
NB: ER - Extended release preparation. eGFR ml/min/1.73m2
P-B M-5 L-6 Alpha-glucosidase inhibitors & DPP-4 inhibitors
3. Alpha-
• These agents competitively block the action of the intestinal enzyme
alpha-glucosidase which breaks down oligosaccharides (break down product of
starch), and thus inhibit the complete digestion of carbohydrate.
• They cause formation of gases due to unabsorbed carbohydrate in the colon.
• Acarbose is poorly absorbed from the gut and extensively metabolized in the
intestinal wall.
• But Miglitol and Voglibose are completely absorbed from the gut and excreted
unchanged.
• Three drugs of this class are currently available:
o Acarbose
o Miglitol
o Voglibose
85
4. DPP-4 inhibitors
• DPP-4 inhibitors are incretin mimetics.
• Mechanism of action:
o DPP-4 inhibitors inhibit action of the DPP-4 enzyme; so delayed clearance of gut
hormone incretins; incretin level remains higher for longer time.
o Incretins lower blood glucose by: a) increasing insulin secretion, b) reducing
glucagon secretion and thus hepatic glucose production, c) slowing gastric
emptying, d) suppressing appetite and food intake.
• Common side effects of DPP-4 inhibitors include:

o Gastrointestinal problems – including nausea, diarrhoea and abdominal pain;
o Flu-like symptoms – headache, runny nose, sore throat;
o Skin reactions – pain followed by red or purple rash and
o Pancreatitis.
• Currently available classes are: Sitagliptin, Vildagliptin, Linagliptin, Saxagliptin,

Alogliptin.
Table showing initiation & dose titration of Alpha-glucosidase

inhibitors & DPP-4 inhibitors for T2DM
Maximum Dose
OAD Class OAD Elimination Starting dose dose adjustment
25-50 mg 300 mg x Increase
x1-3 within (in 3 doses) (on the built
Acarbose Faeces(~98%) meal; build up dose) by
Urine (~2%) up dose smallest
weekly every 6
weeks
25-50 mg 300 mg Increase
Alpha- x1-3 within (in 3 doses) (on the built
glucosidase Miglitol Urine (~100%) meal; build up dose) by
inhibitors up dose smallest
weekly every 6
weeks
0.2 mg x1-3 0.9 mg Increase
within meal, (in 3 doses) (on the built
Voglibose Mostly faeces build up dose up dose) by
weekly smallest
every 6
weeks
86
Maximum Dose
100 mg x1 100 mg I50 mg -
(in 1dose) if eGFR <45;
Sitagliptin Urine (~80%) 25 mg -
if eGFR <30
50 mg x2 100 mg 50 mg -
Vildagliptin Urine (~80%) (in 2 doses) if eGFR <50
DPP-4 5 mg x1 5 mg Full dose in
inhibitors Linagliptin Bile (~80%) (in 1 dose) renal failure
(Gliptin)
2.5 mg x1 5 mg 2.5 mg -
Saxsagliptin Urine (~60%) (in 1 dose) if eGFR <50
25 mg x1 25 mg 12.5 mg -
(in 1 dose) if eGFR <60;
Alogliptin Urine (>70%) 6.25 mg -
if eGFR <30
eGFR ml/min/1.73m2
P-B M-5 L-7 SGLT-2 inhibitors & other OADs
5. SGLT-2 inhibitors
• Currently available classes are: Dapagliflozin, Canagliflozin, Empagliflozin
• The sodium-glucose cotransporter-2 (SGLT-2) is the main site of reabsorption of

filtered glucose in renal tubules. SGLT-2 inhibitors inhibit this SGLT-2 in the proximal
tubules, thus reduce the reabsorption of filtered glucose from the tubular lumen and
lower the renal threshold for glucose.
• Reduction of filtered glucose reabsorption and lowering of renal threshold result in

increased urinary excretion of glucose, ultimately reduction of plasma glucose con
centration.
87
Table showing initiation and dose titration of SGT-2 inhibitors for T2DM
Maximum Dose
5 mg x1, 310 mg Avoid -
morning (in 1 dose) if eGFR <45;
Dapagliflozin Urine (~10%) Stop -
if eGFR <25
100 mg x1, 300 mg 100 mg -

SGLT-2 morning (in 1 dose) if eGFR <60;
inhibitors Canagliflozin Mostly faeces Stop -
(Gliflozin) if eGFR <30
10 mg x1, 25 mg Avoid -
morning (in 1 dose) if eGFR <45;
Empagliflozin Urine & faeces Stop -
if eGFR <30
eGFR ml/min/1.73m2.
6. Others
a) Dopamine-2 agonist - Bromocriptine

• The mechanism of action of dopamine-2 agonist bromocriptine is largely unknown.
• Hypothalamic circadian activities are altered by obesity.
• It is postulated that bromocriptine (when administered during the morning and
released into the systemic circulation in a rapid, ‘pulse-like’ dose) may reset this
circadian rhythm by its dopaminergic activity (on D2 dopamine receptors).
• Bromocriptine results in the reversal of insulin resistance and decrease in glucose
production, without increasing serum insulin concentrations.
b) Bile acid sequestran - Colesevelam
• The exact mechanism of effect on glycemia remains unexplained.
• Colesevelam may reduce hepatic glucose production; and probably affect secretion
of incretin hormones.
88
P-B M-5 L-8 Use of OAD
OAD use in T2DM

For most OADs to have any significant effect, the presence of sufficient amount of insulin
or the ability of the beta cells to secrete endogenous insulin is a must.
Prescriptions of T2DM person are of three types

1. Insulin based (it contains insulin along with lifestyle modification with or without
OADs).
2. Secretagogue based (it contains insulin secretagogues along with lifestyle with or
without other OADs but no insulin) and
3. Lifestyle based (it contains lifestyle modification with or without OADs but
no insulin or insulin secretagogues).
Use of secretagogue based prescription in two situations

1. In newly diagnosed cases with moderately severe glucose intolerance
(HbA1c 8-10% or Fasting blood glucose 11.1-16.7 mmol/L).
2. In old cases when a lifestyle based prescription fails to maintain glycemic target
(HbA1c < 7% in adults).
Use of other OADs

• In general they can be added to all the 3 types of prescriptions.
• Choice of particular molecule depends on its mode of action(s) that are beneficial
for the individual. Hazards and limitations of the molecules are to be considered.
Combination of OADs
• Now it is preferred to combine the second or sometimes the third agent before
maximizing the existing one(s).
• But combination of two secretagogues should be avoided and
• DPP-4 inhibitors cannot be combined with GLP-1 agonists.
Combination of OADs with insulin

• Secretagogues should not be continued in an insulin based prescription if it is a
case of secretagogue failure.
• Other OADs may be used in combination with insulin.
89
OAD (secretagogues) Failure
Failure is said to occur when an orally administered particular anti-diabetic agent does
not produce fall in blood glucose level adequately.
The failure of a drug may be one of two types:

• Primary failure - occurring from initiation of treatment, or
• Secondary failure - after initial control of hyperglycemia with that drug
Primary failure occurs mostly in those who have been diagnosed late in the course of the
disease, and have suffered beta cell exhaustion.
Before defining failure of any particular agent, it is important to consider that the agent
has been used with maximum dose for adequate time to produce its full effect, and other
components of treatment (e.g. diet, exercise) have been practiced properly.
Any of the OADs can fail. When secretagogues fail, it should ultimately be replaced by
insulin. For other agents, addition of another drug or insulin can be done to overcome the
deficient effect.
OAD should not be used in type 2 DM:

• Severe acute complication/illness
• Uncompensated chronic complication/illness
• Pregnancy, lactation, major surgery
• Very high blood glucose
• OAD failure & adverse effect with OAD
90
P-B M-5 L-9 Initiation and dose titration of OADs
Initiation and dose titration of OADs

OADs Dose adjustment
Starting dose Maximum dose (by smallest dose)
Glibenclamide 1.25-2.5 mg x1 dose; 20 mg (in 1-2 doses) every 2 weeks
30 min ac
Glipizide 2.5 mg x1 dose; 30 40 mg (in 1-2 dose) every 2 weeks
min ac
Gliclazide 40 mg x1 dose; 30 320 mg(in 1-2 doses) every 2 weeks
min ac MR 120 mg(in 1dose)
Glimepiride 1 mg x1 dose 8 mg (in 1 dose) every 2 weeks
Repaglinide 0.5 mg x3 doses; 15 12 mg (in 3 doses) every 1-2 weeks
min ac
Nateglinide 60 mg x3 does; 15 360 mg (in 3 doses) every 1-2 weeks
min ac
Metformin 500 mg x1 dose with 2500 mg every 4 weeks
meal; build up the (in 2-3 doses)
dose weekly ER 2000 mg
(in 1 dose)
Pioglitazone 15 mg x1dose 45 mg (in 1dose) every 4-6 weeks
Rosiglitazone 4 mg x1 dose, or 2 8 mg (in 1-2 doses) every 4-6 weeks
mg x1-2doses
Acarbose; 25-50 mg x1-3 doses 300 mg (in 3 doses) every 6 weeks
Miglitol within meal; build up
the dose weekly
Voglibose 0.2 mg x1-3 doses 0.9 mg (in 3 doses) every 6 weeks
within meal; buildup
the dose weekly
Sitagliptin 100 mg x1 dose 100 mg (in 1 dose) 50 mg - if eGFR<45;
25 mg - if eGFR<30
Vildagliptin 50 mg x2 doses 100 mg (in 2 doses) 50 mg - if eGFR<50
Linagliptin 5 mg x1 dose 5 mg (in 1dose) Full dose in renal
failure
Saxsagliptin 2.5 mg x1 dose 5 mg (in 1dose) 2.5 mg - if eGFR<50
Alogliptin 25 mg x1 dose 25 mg (in 1dose) 12.5 mg - if eGFR<60;
6.25 mg - if eGFR<30
Dapagliflozin 5 mg x1 dose, 10 mg (in 1 dose) Avoid - if eGFR<45;
morning Stop - if eGFR<25
Canagliflozin 100 mg x1 dose, 1300 mg (in 1 dose) 100 mg - if eGFR<60;
Empagliflozin 10 mg x1 dose, 125 mg (in 1 dose) Avoid - if eGFR<45;
91
NB: ac - before meal; MR - modified release preparation; ER - extended release
preparation. Various combination preparations are also available. eGFR ml/min/1.73m2.
P-B M-5 L-10 Injectable agents
Insulin is the main injectable agent in treatment of diabetes.

Now-a-days other agents are also available. Injectable agents include:
1. Insulin
2. Other agents
INSULIN preparations for treatment of DM

Type Name Onset of Peak Duration Time with meal
action action of action
Conventional Insulin
Short acting Regular 0.5-1 hr 2-4 hr 6-8 hr 0.5-1 hr ac (higher BG,
more interval)
Intermediate NPH Lente 2-4 hr 6-8 hr 12-18 hr 0.5-1 hr ac or bed time
acting
Long acting Ultralente 4-6 hr 8-14 hr 24-36 hr No specific time
Insulin Analogues
Rapid acting Aspart Lispro Glulisine 5-15 1-1.5 hr 3-4 hr With meals (within 15
analogue min. min ac/pc)
Long acting Glargine Detemir 2-4 hr No 24 hr No specific time
analogue peak
Ultra long acting Degludec 0.5-1.5 hr No 40+ hr No specific time
analogue peak (half life
>24 hr)
Premixed (Biphasic) Insulin
Premix Short & intermediate acting insulin are mixed in different proportions
conventional (30/70%, 50/50%, 25/75%)
Premix Rapid & intermediate acting analogues (protaminated rapid acting
analogue analogue)
are mixed in different proportions (30/70%, 50/50%, 25/75%)
92
Types of insulin according to their blood levels
1. Short/rapid acting (Regular, Aspart, Lispro, Glulisine etc)

2. Basal/long acting (Glargine, Detemir etc)
3. Intermediate acting (NPH)
93
P-B M-5 L-11 Insulin Therapy
INSULIN
• After the discovery of insulin in 1921, it has revolutionized the treatment of diabetes.
• In 1922 the first short of insulin (initially named ‘isletin’, later ‘insulin’) was pushed into
human. Commercial production began in 1923.
• This oldest anti-diabetic agent is still the most potent one.
IIndications of insulin
• Type 1 DM
• Severe acute complication/illness
• Uncompensated chronic complication/illness
• Pregnancy, lactation, major surgery, very high blood glucose
• Failure of or adverse effect with OAD or non-insulin agent
Insulin secretion pattern in a healthy person is continuous basal and meal related bolus
release. Ideal insulin therapy in diabetic should mimic normal secretion pattern.
Insulin regimens are introduced to have that pattern in a diabetic person.

Insulin regimens
a. One injection of intermediate acting
insulin is given in evening or long-acting
insulin analogue is given in morning or
evening.
It serves as basal secretion.
b. It may be effective only in type 2 DM

as monotherapy or in combination with
OAD.
94
Two injections a day
a. Most commonly used regimen.
b. Injections are given before breakfast

and dinner. Any of the following insulins
can be used:
• Intermediate insulin- only in type 2 DM
• Biphasic (premixed) insulin
• including analogue- though convenient
for patients, sometimes it is difficult to
achieve glycemic control with this regi-
men
• Split-mixed (self-mixed) regimen- short
acting insulin or rapid acting insulin ana-
logue is mixed with intermediate acting
insulin in proportions that are adjusted by
trial.
c. When pre-mixed or split-mixed regi-

men is started twice daily, the total daily
dose is divided into morning dose of 2/3rd
and evening dose of 1/3rd with an aim of
providing 2/3rd longer acting insulin with
1/3rd shorter acting insulin.
Multiple injections a day

a. Three to 7 injections per day are used
where there is difficulty in achieving
optimal control with previous regimens.
b. Intermediate acting insulin is given at
bedtime or long acting insulin analogue is
given at bedtime or morning as basal
doses and short acting insulin or rapid
acting insulin analogue is given before
each meal as bolus doses (basal- bolus
regimen).
c. The total daily dose is divided into 50%
longer acting insulin with 50% shorter
acting insulin.
d. This is very flexible and ideal for those
who are very active and cannot comply
with the rigid meal plan or in whom diabe-
tes control is
e. difficult with the above regiments
95
Insulin pump
a. Continuous subcutaneous insulin
infusion (CSII)- small device delivering
insulin at basal rate throughout 24 hours
and patient activated boluses during meal
times through a subcutaneous cannula.
Some of the devices are also equipped
with continuous glucose monitoring
(CGM) system.
b. Used only in selected patients.
Intravenous insulin infusion

Indications:
• DKA; HHS
• Critical illnesses, e.g. acute Ml, stroke
etc.
• Prolonged (>12 hours)
• Nothing Per Oral (NPO) status
• Total Parenteral Nutrition (TPN)
• Perioperative period
• During delivery
P-B M-5 L-12 Insulin administration guideline
Guideline
Insulin regimen and dose for Type 1 DM
Any of the following regiments of insulin can be used.
• Multiple injection regimen (most preferred)
• Split-mixed (self-mixed) regimen
• Premixed regimen (least preferred) and
• Insulin pump
Total insulin replacement is required. Initial total dose is 0.2-0.5 u/kg/day, distributed as
described previously. Increment is made in small doses depending on blood glucose
results.
Insulin regimen and dose for Type 2 DM
Any of regiments of insulin can be used.

The total starting insulin dose is 0.2-0.4 u/kg/day, distributed as described previously.
Increment is made in small doses depending on blood glucose results.
96
P-B M-5 L-13 Insulin administration
Insulin regimens
Once daily Twice daily Multiple injections
Insulin delivery
Syringe Pen device Pump
Insulin injection
Abdomen, upper arms, Subcutaneous fat Needle insertion
thighs, buttocks (least
Absorption of insulin differs at different sites; it is the fastest and highest at the abdom-
inal region, slower at the brachial areas and still slower at the femoral region. These
regional differences are related to differences in tissue perfusion. It is important that
day after day the injection should be pushed into predefined areas and not randomly.
Within the region, injection site is to be rotated. Injection into lipoatrophic sites must be
avoided, as it is likely to be highly unreliable.
Secretagogues with insulin
• Most authorities advocate not use secretagogues with insulin.

• To replace secretagogues with insulin, some prefer to taper the OAD and simultaneous
initiation and increment of insulin dose, with some period of overlapping.
• Patients in whom insulin has been started at diagnosis for symptomatic diabetes or
high blood glucose or acute conditions, OAD can replace insulin, or be added to insulin
when the prevailing conditions are over and when the patient is having stable glycemic
control.
97
P-B M-5 L-14 Insulin administration guideline
Among the other injectable agents GLP-1 agonists (incretin mimetics)

and Amylin analogues are two important ones.
GLP-1 agonists (incretin mimetics)
These are gut hormones or incretins (glucagon-like peptide-1 or GLP-1).

Incretins reduce postprandial glucose increase via:
• increasing insulin secretion and reduce postprandial glucagon secretion resulting in
decreased hepatic glucose production
• slowing gastric emptying
Incretins reduce postprandial glucose increase directly by:
• decreased food intake (appetite suppression)
• increased beta cell growth/replication
Amylin analogues
These are the synthetic analogues of human amylin co-secreted with insulin by pan-
creatic beta cells.
Amylin reduce postprandial glucose increase via:
• prolongation of gastric emptying time
• reduction of postprandial glucagon secretion
Amylin reduce postprandial glucose increase directly by:
• reduction of caloric intake through centrally-mediated appetite suppression.
Hazards of injectable agents

Hypoglycemia, weight gain, lipodystrophy, oedema, allergy
Insulin
(local/systemic)
GLP-1 agonists GI upset; pancreatitis
Amylin analogues Hypoglycemia, GI upset, upper RTI
98
HbA1c lowering potentials of various drugs
Drug Maximum HbA1c (%) reduction
Insulin 2.5 (or more)
Sulfonylurea 1.5
Metformin 1.5
Non-sulfonylurea secretagogue 1.5
Thiazolidinedione 1.4
GLP-1 agonist 1.0
Amylin analogue 1.0
SGLT-2 inhibitor 0.9
Alpha-glucosidase inhibitor 0.8
DPP-4 inhibitor 0.8
Bromocriptine 0.7
Colesevelam 0.5
99
P-B M-5 L-15 Pancreatic transplant
Pancreatic transplant
Pancreas transplantation may be an option in management of diabetes, only in patients
with serious progressive complications e.g. end stage renal disease, having or planning
for kidney transplantation.
It may also be done if there is history of frequent, acute, severe metabolic complications
(hypoglycemia, marked hyperglycemia, ketoacidosis), incapacitating clinical and emotion-
al problems with exogenous insulin therapy, and consistent failure of insulin-based man-
agement to prevent acute complications.
Islet transplantation is an evolving technology; it can be performed only in research
settings.
Pancreas transplantation has a higher rate of insulin independence and morbidity than
islet transplantation.
Transplantation for diabetes management
Pancreas transplantation Pancreas plus kidney Islet transplantation

transplantation
100
P-B M-5 L-16 Diabetic education
Diabetes self management education (DSME) or diabetes education is an integral compo-

nent of effective diabetes management. The diabetic patients should be trained in self
management skills. Otherwise there will be no coordination among the other components
of management, notably MNT, exercise, drugs, monitoring etc.
• The patients are to be educated immediately after detection of diabetes.

• At least 10 hours of initial education is required in multiple sessions over 3 months.
DSME Curriculum
1. The curriculum of diabetes education should include ideas about

• Basic concepts of the disease and its complications,
• Dietary measure,
• Physical activity,
• Drug therapy,
• Skill development on glucometer use, insulin administration, foot care, sick day’s
management etc.
2. Members of diabetes education team are Physician/diabetologist, diabetes spe

cialist nurse, nutritionist, psychologist and some other health care professionals.
3. Education material: Each patient should have a booklet (preferably in own

language) which will contain all the education materials for a diabetic.
DSME materials
Booklet Diet charts of different daily calories
Booklet Diet charts of different daily calories
101
Charts (pictorial) for carbohydrate, fat & Instructions for insulin injection
protein exchange & preservation
There are 15 Lessons in Module 5. I understand the following points:

• The mechanism of action and maximum doses of various anti-diabetic agents.
• The appropriate time to commence drug treatment and types of drugs to be used in
different clinical situations.
• How to identify failure of oral anti-diabetic agents.
• Selection of appropriate regimen of insulin for a patient.
• How to provide hands-on training on insulin administration to patients and their family
members.
Further reading
1. Textbook of Diabetes, 4th edition, edited by Richard l G Holt, Clive S Cockram, Allan
2. Davidson’s Diabetes Mellitus- Diagnosis & Treatment, 5th edition, edited by A P
Har mel& R Mathur, Saunders, 2004.
3. Clinical Diabetes - Translating Research into Practice, 1st edition, VA Fonseca, \
Saunders, 2006.
4. Clinical Practice Recommendations, ADA (American Diabetes Association), 2018.
5. Global Guideline for Type2 Diabetes, Clinical Guidelines Task Force, IDF
(International Diabetes Federation), 2012.
Clinical Endocrinologists) Task Force, 2017.
102
Module-6
Acute Complications of
Diabetes Mellitus
103
Objective
1. To identify DKA along with its cause and/ or precipitating factors; thereby to
initiate its treatment.
2. To identify HONK along with its cause and/ or precipitating factors; thereby to
3. To have some idea about lactic acidosis and glycemic management of critically ill
patients.
4. To diagnose and treat cases of hypoglycemia and educate the patient how to
prevent hypoglycemia.
P-B M-6 L-2 Acute complications of DM
The complications of diabetes mellitus may be acute or chronic. The acute complications
are related to immediate and rapid changes in metabolism that arise within a short time
(hours to weeks).
Acute complications
1. To identify DKA along with its cause and/ or precipitating factors; thereby to initi
ate its treatment.
2. To identify HONK along with its cause and/ or precipitating factors; thereby to
3. To have some idea about lactic acidosis and glycemic management of critically ill
patients.
4. To diagnose and treat cases of hypoglycemia and educate the patient how to
prevent hypoglycemia.
• The acute complications are to some extent preventable and require immediate
medical attention.
• The chronic complications occur after a long period (usually in terms of years) of
uncontrolled diabetes.
• Main chronic complications are micro-vascular and macro-vascular diseases.
104
P-B M-6 L-3 DKA & its cause
Diabetic ketoacidosis (DKA)
• Diabetic ketoacidosis (DKA) is a medical emergency in diabetic patients.

• It is commonly found in type1 DM. But it also occurs in other types of diabetes
during stressful situations.
• It results from lack of insulin and rise in counter-regulatory hormones that lead to
hyperglycaemia and subsequent lipolysis.
Causes of DKA
1. Undiagnosed diabetes
2. Omission of insulin dose.
3. Injudicious reduction of insulin dose
4. Intercurrent illness, especially acute infection
5. Trauma
6. Pregnancy, etc.
P-B M-6 L-4 Clinical feature & diagnosis of DKA
Clinical feature of DKA
1. DKA develops rapidly (hours todays)

2. Symptoms of uncontrolled diabetes precedes
3. Weakness, vomiting, impairment of level of consciousness, acute abdomen
4. Dehydration is the most obvious clinical feature with dry skin and tongue, low BP,
rapid weak pulse
5. Acidotic breathing is characteristic; there may be acetone smell inbreath
Diagnosis of DKA by biochemical features
• Blood glucose – usually > 15 mmol/L

• Acidosis – arterial pH < 7.3; plasma bicarbonate <15 meq/L
• Ketone bodies in blood and urine are greatly increased
• Serum osmolality is variable
105
P-B M-6 L-5 Management (Principle) of DKA
Principle of Management of DKA
• Hospitalization
• Clinical assessment
• Determination of blood glucose, electrolytes, arterial blood gas with pH, osmolality
• Complete blood picture, urea etc.
• Blood/urine for ketone body
• Treatment institution is to be done immediately without waiting for laboratory reports.
Treatment components of DKA Management
• Fluidreplacement
• Insulin
• Potassiumreplacement
• Bicarbonate use
• Monitoring -clinically, biochemically and othersand
• Nursingcare
P-B M-6 L-6 Management of DKA
Management of DKA
Fluid replacement:
• To infuse initially normal saline (0.9% NaCl) rapidly, then 0.9% or 0.45% NaCl
calculating against clinical and biochemical status.
• When blood glucose comes down to 14.0mmol/L, 5% dextrose is to be started.
Short acting insulin.

• If infusion pump is available, infused at a rate of 0.1 unit/kg/ hour; otherwise,
10-20 units bolus i.m. is given, followed by 0.1 unit per kg i.m. hourly.
• Hourly fall of blood glucose should be in the range of 3-4 mmol/L; otherwise,
insulin dose should be increased.
• Insulin dose is reduced when blood glucose comes to 14.0 mmol/L.
• Usual sub-cutaneous regimen of insulin may be started when the patient stable
clinically and biochemically, and able to take oral food
106
Potassium replacement depends on blood level of K+.
• If blood level of K+ <3.5 mmol/L– 40 mmol/hr. K+ Infusion
• If blood level of K+ 3.5-5.5 mmol/L – 20 mmol/ hr. K+ Infusion in each litre of fluid
• If blood level of K+ >5.5 mmol/L – Not to give K+
Sodium bicarbonate
• In severely acidotic patient (pH <7.0) sodium bicarbonate is to be infused slowly.
Proper nursingcare
Monitoring:
• Assessment of Clinical condition,
• Blood glucose, electrolytes, arterial blood gas frequently (1-4 hourly) until stable,
• Blood/urine ketone and
• Other tests as required
P-B M-6 L-7 Complications of DKA
Complications of DKA
1. Cerebral oedema
2. Circulatory failure
3. Thromboembolism,
4. DIC, etc.
Overall mortality for DKA is 2% or less.
P-B M-6 L-8 HONK and its Causes
Hyperosmolar nonketotic coma (HONK) (Hyperglycemic hyperosmolar state-HHS)
• HONK is a combination of a) severe degree of hyperglycemia, b) dehydration and

c) hyperosmolality, without significant ketonuria.
• Usually seen as complication of elderly type2 DM patients.
• Here residual insulin reserve prevents ketosis.
107
Causes of HONK
• Lack of proper treatment of diabetes

• Any acute stress, e.g., infection, stroke, myocardial infarction, trauma
• Compromised fluid intake
• Drugs, e.g., glucocorticoids, diuretics.
P-B M-6 L-9 Clinical feature & diagnosis of HONK
Clinical features of HONK
• Develops slowly (days to weeks)

• Symptoms of uncontrolled diabetes precede
• Dehydration is profound
• Impairment of consciousness is common
Diagnosis of HONK
• Blood glucose – usually > 30 mmol/L

• Hyperosmolality – effective serum osmolality > 320mosm/kg
• No acidosis – arterial pH > 7.3; plasma bicarbonate > 15meq/L
• Absence of significant ketonemia/ketonuria
P-B M-6 L-10 Management of HONK
Principles of Management of HONK
• Hospitalization
• Clinical assessment
• Determination of blood glucose, osmolality, electrolytes, arterial blood gas with pH
• Complete blood picture, urea etc.
• Treatment institution is to be done immediately without waiting for laboratory reports.
108
Management of HONK
Treatment and monitoring are very similar to DKA except few points:
• rapid change in plasma osmolality should be checked
• less insulin is required than DKA
• 5% dextrose and lower insulin dose are started at a higher blood glucose level
• sodium bicarbonate is not required
Complications of HONK
Complications of HONK are similar to that of DKA

• Cerebral oedema
• Circulatory failure
• Thromboembolism, DIC, etc.
• Overall mortality for HONK is 10 -20%
P-B M-6 L-11 Lactic acidosis
• Impaired tissue oxygenation, leading to increased anaerobic metabolism, is usually

responsible for lactic acidosis.
• It may be precipitated by hypovolemia, cardiac failure. Cardiopulmonary arrest,
sepsis, various drugs (including metformin) alcoholism, severe infection, hepatic
failure, malignancy etc.
• In Diabetes mellitus lactic acidosis can be precipitated by:
o biguanide therapy, although the risk is very low; or
o sometimes in diabetic ketoacidosis (DKA), probably due to hypovolemia.
Features of Lactic acidosis
• The onset may be rapid (minutes to hours) or progressive (several days).

• Patients present with severe dehydration, marked acidosis, mild (or no) ketonuria etc
• Diagnostic feature: Plasma lactate concentration exceeds 4meq/L.
109
P-B M-6 L-12 Treatment of Lactic acidosis
Treatment of Lactic acidosis consist of
• Fluid replacement,
• Correction of acidosis,
• Improvement of tissue perfusion,
• Control of blood glucose
• Correction of the precipitating factor,
• Other supportive measures etc.
Mortality rate is very high, may be up to 75% in severe cases
P-B M-6 L-13 Hypoglycemia
Hypoglycemia
• It is defined biochemically with blood glucose level below 70 mg/dl (4.0 mmol/L) with
clinical features of neuroglycopenia and autonomic overactivity.
• However, some diabetics, specially those with high blood glucose, may develop
clinical features (particularly autonomic) of hypoglycemia at a higher blood glucose
level due to relative hypoglycemia.
• Hypoglycemia is a very common phenomenon in diabetes. It occurs much in T1DM

than T2DM.
110
Hypoglycemia
Clinical features depend on hormonal and neural response to hypoglycemia and called
Autonomic features and Neuroglycopenic features respective
Autonomic features (also called ‘warning symptoms’)
These are due to response of adrenal glands and sympathetic nervous system to low
blood glucose.
1. Sweating
2. Palpitation
3. Tremor
4. Irritability
5. Hunger
Neuroglycopenic features
These are due to disturbance of central nervous system from low glucose availability.
1. Headache
2. Confusion
3. Visual disturbances
4. Behavioural abnormality
5. Drowsiness
6. Convulsion
7. Coma
P-B M-6 L-14 Severity of Hypoglycemia
Severity of Hypoglycemia (based on Clinical features)
Hypoglycemia may vary from mild to severe. In severe hypoglycemia the affected indi-
vidual requires assistance of another person and cannot be treated with oral carbohy-
drate due to confusion or impaired consciousness
111
Severity of Hypoglycemia (based on Clinical features)
Mild to moderate
Type of Features TSevere Hypoglycemia
Hypoglycemia
Sweating Palpitation Absent
Autonomic Tremor
Irritability Hunger
Headache Confusion
Neuroglycopenic Visual disturbances Drowsiness
Behavioral abnormality
Convulsion
Coma
P-B M-6 L-15 Unaware hypoglycemia and Nocturnal hypoglycemia
Unaware hypoglycemia and Nocturnal hypoglycemia
• Individuals with long-standing type1 diabetes,

• Autonomic neuropathy,
• Medication (like non-selective beta-blockers) or
• very strict glycemic control may not have warning symptoms.
Nocturnal hypoglycemia
• Night-time hypoglycemia, usually occurring between 2 and 4am

• Patients or their relatives may be awakened due to trembling or sweating.
• Sometimes the patient may have morning headache, dizziness, forgetfulness, and
confusion.
• Confirmation of the suspected condition is made by blood test at appropriate time.
112
P-B M-6 L-16 Causes of hypoglycemia in a diabetic
Causes of hypoglycemia in a diabetic
• Administration of too much insulin

• Excess intake of insulin secretagogues
• Delay or omission of a meal
• Doing more exercise than usual
• Overindulgence in alcohol
• Severe impairment of renal or hepatic function
P-B M-6 L-17 Treatment of hypoglycemia
Treatment of hypoglycemia is according to its severity and type
Mild to moderate hypoglycemia
• Most cases are treated by the patient him/herself or by a family member.

• It is usually relieved by 15 gm glucose or equivalent food, e.g.
o A glass of soft drink or fruit juice or snacks or meal (if it is due).
o These measures are usually adequate to raise blood glucose to reasonably
safe limit (5.5 mmol/L).
o The food/drink is repeated every 15 minutes until the patient is stable.
• If recurrent hypoglycemia follows, hospitalization is to be considered as in a case of
severe hypoglycemia.
• Modification in treatment may be required.
113
Severe hypoglycemia
• Diagnosis is made with a finger prick.

• Injection glucagon 1 mg intramuscularly or subcutaneously may be given. 50-100
mal of 25% dextrose is given intravenously, for which hospitalization maybe required.
• If hypoglycemia is due to longer acting anti-diabetic medications, then 10% dextrose

infusion should be started to prevent recurrent hypoglycemia.
• Ongoing activity of the anti-diabetic medication may lead to recurrence of

hypoglycemia; so food ingestion is to be ensured after initial recovery.
• If recovery does not occur search for additional causes and modification in
treatment should be done.
Nocturnal hypoglycemia:
• Reduction of evening dose of insulin.

• Changing the time of evening insulin dose with dinner time.
• Bed time snacks may help.
• These adjustments are made in conjunction with blood glucose monitoring.
Unaware hypoglycemia
• Frequent blood glucose monitoring to prevent and treat severe hypoglycemia.

• Each patient with hypoglycemia should be evaluated and provided with appropriate
education to prevent and manage future episodes.
Consequences of ‘hypoglycemia’
• Recurrent hypoglycemia may cause behavioral change and cognitive impairment.

• In T2DM – increased incidence of life-threatening cardiovascular events and mortali
ty (cardiovascular and all cause).
• In T1DM – increased mortality (4-10% of deaths).
114
P-B M-6 L-18 Glycemic management of critically ill patients
Glycemic management of critically ill patients
• Insulin should be initiated for persistent hyperglycemia at blood glucose >10.0

mmol/L in critically ill patients.
• Once insulin is started blood glucose level should be maintained at 7.8 – 10.0
mmol/L for the majority of critically ill patients. More stringent goals may be appro
priate for selected patients if this can be achieved without significant hypoglycemia.
But blood glucose <6.1 mmol/L is not recommended.
• For majority of critically ill patients in ICU setting insulin infusion should be sued to
control hyperglycemia.
There are 17 Lessons in this module 6. I understand the following points:

1. How to identify DKA along with its cause and/ or precipitating factors; thereby to
2. How to identify HONK along with its cause and/ or precipitating factors; thereby to
3. I know about lactic acidosis and glycemic management of critically ill patients.
4. How to diagnose and treat cases of hypoglycemia and educate the patient how to
prevent hypoglycemia
Further reading
1. Text Book of Diabetes, 4th edition, edited by Richard l G Holt, Clive S Cockram, Allan
Flyvbjerg & Barry J Goldstein, Wiley-Blackwell, 2010
2. Davidson’s Diabetes Mellitus- Diagnosis & Treatment, 5th edition, edited by A P Harmel
& R Mathur, Saunders, 2004.
3. Clinical Diabetes- Translating Research into Practice, 1st edition, VA Fonseca,
Saunders, 2006.
5. Global Guideline for Type2 Diabetes, Clinical Guidelines Task Force, IDF (International
6. Comprehensive Diabetes Management Algorithm,
AACE (American Association of Clinical Endocrinologists) Task Force, 2017.
115
Module-7
Microvascular Complications of
Diabetes Mellitus
116
Objective
1. To enumerate the micro-vascular complications of diabetes mellitus and discuss

their pathogenesis.
2. To detect and manage various types of diabetic retinopathies.
3. To detect and manage diabetic nephropathy.
4. To detect and manage various types of diabetic neuropathies.
P-B M-7 L-2 Introduction
Chronic complications of diabetes mellitus
Diabetes mellitus is a chronic, debilitating disease, which is associated with a range of

severe complications. Diabetes mellitus as a disease has earned its importance by its
wide spread complications.
• Chronic complications produce changes in small or large vessels of the body.

Accordingly, these complications are grouped into two types:
o Micro-vascular complications or microangiopathy (when smaller vessels, e.g.
capillaries are affected) and
o Macro-vascular complications or macroangiopathy (when bigger vessels
are affected)
• Hyperglycemia is the principal risk factor to develop micro- and macro-angiopathies

in a diabetic individual. Both the lesions result in organ dysfunctions.
• Early detection of these angiopathies and meticulous management to prevent compli
cations is the major challenge of diabetes care.
• Magnitude and pattern of complications are changing with time.

• During pre-insulin era, life expectancy was very short due to acute metabolic compli
cations, like ketoacidosis.
• However, with the discovery of insulin and subsequently other drugs, lives of diabetic
patients have been prolonged, exposing the patients to chronic complications, some
of which may lead to premature death or considerable morbidity.
117
• Complications may be present at detection of diabetes.
• Routine/annual health check-up programs pick up significant of diabetic subjects with
chronic complications.
• Many studies namely DCCT (in T1DM), and UKPDS and ADVANCE (in T2DM), have
shown that the morbidity as well as mortality risks associated with diabetes can be
reduced by treating to its targets.
P-B M-7 L-3 Factors affecting Microangiopathy
Factors affecting Microangiopathy
1. Duration of diabetes: Microangiopathies of DM generally increase with duration of

diabetes.
• In type1 DM they are rarely seen before 5-7 years. Microangiopathies occurs
usually after 10 years or more.
• T2DM people often have a long undiagnosed period and therefore significant
proportions may have one or more microangiopathies at diagnosis of diabetes,
their prevalence increases with duration of diabetes.
2. Status of glycemic control (blood glucose or HbA1c): strongly related to both micro
and microangiopathies of diabetes.
• Numerous studies have proved that good control of blood glucose reduces the rate
of development of complications.
• But some diabetics do not seem to be affected by complications regardless of
their duration or metabolic control.
3. Other factors
• Genetic susceptibility to certain complications may be present.

• Age may be related to some complications.
• Hypertension and dyslipidemia are the two very important modifiable factors in the
development of both micro and microangiopathiesg1in a diabetic person.
All these factors should be taken into account during prevention and treatment of
complications.
118
P-B M-7 L-4 Mechanism of Microangiopathy
Micro-vascular complications/ Diabetic micro-angiopathy: Proposed

Mechanisms (by hyperglycemia)
Changes due to Hyperglycemia
• Increased glycation leading to accumulation of basement membrane collagen and
membrane leakiness.
• Stimulation of intracellular polyol pathway (with production of sorbitol) leading to
basement membrane and capillary endothelial cell damage.
• Accumulation of a number of other chemical substances, e.g. Advanced
Glycosylation End products (AGEs), free radicals etc.
Overall effects of Hyperglycemia

• Capillary basement membrane ethickening
• Protein leakage
• Microthrombus formation
• Tissue ischemia
Organ affected by microangiopathy

• Kidneys- leads to nephropathy
• Eyes- leads to retinopathy
• Peripheral nerves- leads to neuropathy (together with chemical, mainly, sorbitol).
Major organ problems by microangiopathy in diabetes mellitus in

comparison to normal
Problems Prevalence
Blindness 25 times
Kidney failure 5 times
Lower limb amputation 20 times
119
P-B M-7 L-5 Diabetic retinopathy (DR)
Diabetic Retinopathy (DR)

It is a specific form of micro-angiopathy of retina with one or more of the following
lesions:
1. Microaneurysm
2. Haemorrhage
3. Exudate
4. New vessel formation
Early changes may be asymptomatic, but later may even lead to blindness. Diabetic
retinopathy is the leading cause of blindness. Some degree of retinopathy is evident
after 30 years in 87-98% T1DM and after 15 years in 60 - 85% of T2DM.
Diagnosis of DR and classification of DR is done on the basis of findings of
a) Fundoscopy,
b) Stereoscopic color fundus photography
c) Fluorescein angiography.
Features of Normal Eye
Stereoscopic Colour
Fundoscopy Fundus Photography Fluorescein angiography
120
Fundoscopy & Photography:
• Disc: 1. margins sharp, 2. color: yellowish orange to creamy pink, 3. shape: round or
oval,
• 4. Cup to disc ratio: < .5.
• Vessels: 1. AV ratio, 2. AV crossing: no indentation, 3. No arterial light reflex
• Fundus background: 1. No exudates or hemorrhages, 2. color : red to purplish
• Macula: 1. macula is located 2.5 disc distance temporal to disc, 2. no vessels are noted
around Macula, 3. it may be slightly pigmented
Fluorescein angiography:
1. Blood vessels will have normal shape and size,
2. No blockages or leaks in the vessels.
121
P-B M-7 L-6 Classification of DR
Classification of Diabetic retinopathy (DR)
Classification of Diabetic retinopathy is on the basis of the lesions that are documented
in eye examination.
Lesions in an advance or severe class of DR may or may not have the lesion(s) of
preceding class. For example PDR = Lesion(s) of PDR (+Lesion(s) of NPDR)
The table below is the summery of classes of DR
Class of DR Description/ Lesions
1. Microaneurysm
Early Non-Proliferative Diabetic
2. Dot & blot haemorrhage
Retinopathy (NPDR)
3. Hard exudates
1. Cotton wool spots/soft exudates
Moderate to severe NPDR 2. Venous beads & loops

3. Intra-Retinal Microvascular Abnormalities (IRMA)
1. Neovascularization of Disc - NVD
Proliferative Diabetic 2. Neovascularization of elsewhere - NVE

Retinopathy (PDR)
3. Vitreous haemorrhage
4. Tractional retinal detachment
In and around the macula-
1. Oedema,
Maculopathy
2. Exudate
3. Haemorrhage
122
P-B M-7 L-7 Lesions in different class of DR
Diabetic Retinopathy (DR)
• Non-proliferative diabetic retinopathy (NPDR)

o NPDR is again sub classified as early, moderate to severe NPDR depending on the
type of lesions.
• Proliferative diabetic retinopathy(PDR).
• Specific lesions (Oedema, exudate & haemorrhage) in and around the macula is
called Maculopathy.
The tables below show lesions in different classes of DR.
NPDR (Early) NPDR (Moderate to severe)
1. Microaneurysm: Small red dots, often 1. Cotton wool spots/soft exudates:

in punctate pattern. white spots or patches (composed of
exoplasm& organelles of nerve fibers)
2. Dot & blot haemorrhage: Red round or indicating localized retinal ischemia.
blot shaped in the inner nuclear layer, or
flame shaped in nerve fibre layer. 2. Venous beads & loops: of retinal
veins.
3. Hard exudates: yellowish specks or
patches of lipid - protein mixture 3. IRMA (Intraretinal microvascular
abnormalities): loops of fine vessels
arising from either major arteries or veins.
123
PDR Maculopathy
1. NVD: Large bundles of new vessels on the optic nerve- Oedema, exudate &
head. haemorrhage in and
2. NVE: Large bundles of new vessels on the periphery of around macula
retina.
3. Vitreous haemorrhage: Vitreous is cloudy or opaque
and often has reddish hue.
4. Tractional retinal detachment: loss of vision if macula
involve
P-B M-7 L-8 Evaluation and Treatment
Evaluation
• Visual acuity should be checked routinely.

• Direct ophthalmoscopy should be done.
• Indirect ophthalmoscopy to be done if media is hazy and when peripheral lesions are
anticipated.
• Fundus photography and drawing - to document haemorrhage, exudate, oedema and
new vessels.
• Fluorescein angiogram - to evaluate:
• Ischemic retinal leakage
• Neovascularization and
• Unexplained reduction of vision
124
Treatment
1. Metabolic control • Good metabolic control reduces the incidence of diabetic

retinopathy and delays its progression significantly.
2. Control of • It is very important because uncontrolled hypertension

Hypertension causes rapid progression of diabetic retinopathy.
3. Panretinal • Patient with proliferative diabetic retinopathy are treated

Photocoagulation (PRP) by PRP with Argon laser.
• In this procedure a series of 1200 to 1600 laser burns of
500 micrometers of diameter are applied in the mid-
peripheral retina ( avoiding macular region).
• This procedure can reduce the rate of progression to
blindness by about 50%.
4. Vitrectomy • It is done in advance cases of proliferative diabetic
retinopathy.
• It often restores useful vision of eyes that would other-
wise be blind.
5. Pharmacotherapy • Drugs such as aldose reductase inhibitors are being tried

to reduce the progression of diabetic retinopathy with vari-
able success.
• Anti-vascular endothelial growth factor (VEGF) is promis-
ing in prevention of vision loss in Proliferative Diabetic
Retinopathy.
125
P-B M-7 L-9 Other changes in eye
Other changes in eye of diabetics

Cataract and glaucoma occur earlier and more frequently in diabetics than
non-diabetics
1. Cataract: Premature Cataract Snow-Flake Cataract
• Similar to senile cataract;

but changes are accelerat-
ed and occurs prematurely.
• Very rarely, diabetes

specific ‘snow-flake cata-
ract’ occurs in young sub-
jects
2. Glaucoma: Secondary Glaucoma Rubeosisiridis
• Secondary (angle-clo-
sure) glaucoma develops
due to blockage of aqueous
flow by new vessels on
anterior surface of iris
(rubeosisiridis).
126
P-B M-7 L-10 Decision Making Path of DR
Decision making path of Diabetic Retinopathy Management (5 steps)

Decision making path of Diabetic Retinopathy Management
• in T2DM at diagnosis and then once a
year.
Eye Evaluation in diabetic
Step 1 • in T1DM at diagnosis and after 5 years
person (Schedule)
or earlier (when no retinopathy is docu-
mented).
Dilated eye examination for
Step 2 Direct Ophthalmoscopy
retinopathy
Documentation & Indirect Ophthalmoscopy, angiogram,
Step 3
classification of retinopathy fundus photo etc.
a. Establish and maintain

• HbA1c <7%,
Step 4 Care strategies
• Maintain BP<140/80 mm ofHg
b. Look for other micro-angiopathies
Establish joint care if the retinopathy is
Step 5 Referral to ophthalmologist
beyond early NPDR
P-B M-7 L-11 Diabetic nephropathy (DN)
Diabetic nephropathy (DN)

DN is a specific form of micro-angiopathy of kidney with hallmarks of:
1. Persistent loss of albumin in urine and
2. Progressive renal insufficiency with or without
3. Hypertension
• Diabetic nephropathy is the leading cause of end-stage renal failure (ESRD) in the
world.
• Approximately 30% of T1DM will eventually develop diabetic nephropathy.
• Nephropathy is less common in T2DM (15-20%) than T1DM, but due to the greater
number of T2DM, the majority of patients with ESRD are T2DM.
127
P-B M-7 L-12 Diabetic nephropathy
Diagnosis of Diabetic nephropathy (DN)

• A diabetic person is diagnosed to have DN upon documenting hall marks of DN.
• Persistent loss of albumin in urine and progressive renal insufficiency with or without
hypertension are the hall mark of DN.
• DN has a progressive natural history. In early stage it is asymptomatic, which
progresses to end stage renal failure (ESRD) passing through some intermediate
stages.
Hallmark Diabetic Nephropathy
1 A diabetic person with persistent Urinary albumin: > 200 mcg/min or > 300
albumin loss in urine and mg/day
a. declining Glomerular Filtration Rate
Progressive renal insufficiency (GFR)
2
b. declining Creatinine Clearance Rate
(CCR)
1 Hypertension (may or may not be)
Ideally diagnosis of DN depends on documentation of diabetic specific

changes in kidney biopsy material.
Tests use for DN diagnosis
Sl Test Result/value Remark

Urinary Albumin Excretion • < 20 mcg/min or < 30
(UAE mg/day = Normal
• 20 to < 200 mcg/min or
1 30 to < 300 mg/day
= Microalbuminuria
• ≥200 mcg/min or > 300
mg/day
= Overt proteinuria
Estimated Glomerular • 100 - 130 ml/min/1.73

Filtration Rate (eGFR) sq. M for adult male and
2
• 90 - 120 ml/min/1.73
sq. M for adult female
128
Estimated Creatinine • Cockcroft-Gault formu Indirect estimation
Clearance Rate (eCCR) la= (140-Age) x Weight GFR
(in Kg) x 72.
• For women: to multiply
3 by 0.85.
• Normal value: 97 to 137
mL/min for male and 88
to 128 mL/min for
female
Albumin-Creatinine Ratio Normal value: <30 micro- Preferred Method

4 (ACR) gram/mg (It matches with
Microalbuminuria)
Kidney Biopsy Glomerular size increased, Reserve for specific

basement membrane cases.
thickens, mesangial
5
proliferation, glomerular
sclerosis (Kimmelstiel-
Wilson lesion) etc.
129
P-B M-7 L-13 Staging of DN
Stages of Diabetic Nephropathy

• Staging of diabetic nephropathy is an essential step in management. There are two
commonly use system of staging of diabetic nephropathy
• GFR based staging and b. combining GFR , UAE Rate, BP and Histological changes
together (adopted from Mogensen).
a. Staging of DN by GFR
Stages of DN / CKD by GFR
Stage Description GFR (ml/minute)
1 Renal damage + Normal/raised GFR > 90
2 Renal damage + mild decreased GFR 60 to 89
3 Moderately decreased GFR 30 to 59
4 Severely decreased GFR 15 to 29
5 Kidney failure < 15 or on dialysis
b. Staging of DN by combing UAE, BP, GFR, and Histological changes.

Stages of DN (adopted from Mogensen 1999)
Stage UAE BP GFR Histology

(mcg/min)
1. < 20 Normal Increased by 20 - Increased glomerular size
Hyperfiltration 50%
2. < 20 Normal Increased Basemen Membrane (BM)

Normoalbu- thickening
minuria
3. 20 - <200 Normal/elevated Still high, but start BM thickening with

Microalbu- declining mesangial proliferation
minuria
4. > 200 Elevated Reduced Pronounced & progressive

Overt abnormalities.
proteinuria
5. > 200 Elevated Reduced Advanced abnormalities

Renal Failure
130
P-B M-7 L-14 Renal Function evaluation in DM
Renal Function evaluation in DM

Structured evaluation strategies for prevention and early detection of complication in
diabetes care protocol have brightened the dream of complication-free life for people
with diabetes. Renal function evaluation is one of the most prioritized issues in diabetic
management.
Stages of DN / CKD by GFR
Stage Tests Schedule

Full clinical check-up, spe- during each visit
1 cially blood pressure, pedal
oedema etc.
2 UAE Two of three samples of UAE abnormal in

3-6 months
Blood urea, creatinine, If UAE abnormal or at least once in every
3 protein, electrolytes, eGFR, year (Otherwise screening and follow-up
CCr and ACR estimation. with only urine albumin will miss> 20% of
progressive renal disease).
Monitoring of other urinary If bladder dysfunction (autonomic blad-
4 complications der) etc or at least once in every 6/ 12
e.g. UTI months
Monitoring by sonogra- If DN present at least once in every 6
phy-kidney size, progressive months of advice of nephrologist.
5 increase in echogenicity of
cortex.
Renal biopsy Indicated in nephropathy
In absence of retinopathy,
6 Heavy proteinuria,
Rapid unexplained deterioration of renal
function etc
131
P-B M-7 L-15 Treatment of DN
Treatment of Diabetic Nephropathy

Treatment of DN
1 Treatment of DN Good metabolic control
reduces
• incidence of diabetic
nephropathy and
• Delaysits progression
significantly.
2 Control of • Uncontrolled hypertension • Target of BP is <140/80 mm

hypertension causes rapid progression of of Hg.
diabetic nephropathy and • Intensive and combination
• Nephropathy itself makes regimens are often needed.
hypertension refractory to • ACE inhibitors and ARBs are
antihypertensive drugs. Thus, drugs of first choice to reduce
necessitates intensive and or revert nephropathy, (these
combination regimens. two drugs must not be
combined).
3 Dietary protein • Protein intake up to • Protein restriction is not
restriction • 0.8 gm/kg/day of ideal body required in early nephropathy
weight may be appropriate in
advanced kidney disease.
4 Fluid and • Should be maintained
electrolyte balance
5 Treatment of • Iron supplementation often
anaemia fails to correct anaemia in
renal failure.
• Iron along with erythropoie-
tin provide optimum response.
6 Renal replacement • Should start earlier (CCr 15 Renal replacement therapy

therapy: ml/ min unlike 10 ml/min in includes dialysis and renal
• non-diabetic) because most transplantation.
patients with ESRD have • Dialysis comprises hemodi-
severe organ involvement and alysis and peritoneal dialysis
fluid overload are often diffi- (intermittent or continuous
cult to treat. ambulatory peritoneal
dialysis).
• Renal transplantation com-
prises only kidney transplanta-
tion and dual transplantation
of pancreas with kidney.
132
P-B M-7 L-16 Decision making path of DN
Decision making path of Diabetic Nephropathy Management (5 steps)

Decision making path of Diabetic Nephropathy Management
Kidney Evaluation in diabetic • In T2DM at diagnosis and then once a
person (Schedule) year.
Step 1 • In T1DM at diagnosis and after 5 years
or earlier. (when no nephropathy is docu-
mented).
Step 2 Screening tests Urinary albumin and serum creatinine
Documentation & a. eGFR, CCr and ACR estimation.

Step 3 classification/staging of b. Ultra-sonogram, biopsy (if indicated)
nephropathy
Care strategies a. Establish and maintain
• HbA1c <7%,
Step 4
• Maintain BP<140/80 mm of Hg
Referral to nephrologist Establish joint care if the nephropathy is
Step 5 at CKD stage 4
P-B M-7 L-17 Diabetic Neuropathy
Diabetic Neuropathy
Diabetic neuropathy is a descriptive term that denotes demonstrable (either clinical or
sub-clinical) evidence of peripheral or autonomic neuropathy in a diabetic individual.
Diabetic polyneuropathy is the most common neuropathy. Approximately 50% of

patients with diabetes eventually develops neuropathy.
Classification of Diabetic neuropathy:

1. Somatic neuropathyand
2. Autonomicneuropathy
133
Diabetic Neuropathy
1. Chronic/insidious sensory neuropathy
2. Acute painful neuropathy and Diabetic amyotrophy
Somatic neuropathy
3. Diffuse motor neuropathy
4. Focal neuropathies
1. Gastroparesis
2. Diabetic diarrhoea
3. Impotence (in male)
Autonomic neuropathy
4. Gustatory Sweating
5. Neurogenic Bladder
6. Impaired Cardiovascular reflexes’
134
P-B M-7 L-18 Somatic Neuropathy
Diabetic Neuropathy (Somatic)

1. Chronic/insidious sensory neuropathy:
• Progressive development of unpleasant sensations
• Pain and hyperesthesia in legs and feet
• Associated muscle wasting and autonomic dysfunctions are common
2. Acute painful neuropathy and diabetic amyotrophy:
• Sudden onset of pain in legs and/ or thighs
• Usually, unilateral amyotrophy
• Severe muscle wasting may lead to severe weight loss
• No sensory loss
• These often begin during hyperglycemia; may improve on strict control of blood
glucose
3. Diffuse motor neuropathy
• Severe, generalized muscle wasting and weakness
• No pain or sensory loss
• Recovery is poor
4. Focal neuropathies
Occur due to pressure damage or vascular damage.
• Examples Pressure damage – median nerve, common peroneal nerve
• Examples Vascular damage – III, IV VI, VII nerve palsies, phrenic and thoracic nerve
palsies
135
P-B M-7 L-19 Diabetic Neuropathy (Autonomic)
Diabetic neuropathy (Autonomic)

1. Gastroparesis
Delayed emptying or retention of gastric contents may lead to nausea, vomiting, abdom-
inal discomfort.
2. Diabetic diarrhoea
Bacterial overgrowth from stasis in small intestine may lead to passage of large volume
of watery stool even in bed at night.
3. Impotence (in male)
Diabetes is responsible for about 15% cases of total number of impotence. It may be
combination of neuropathy and vasculopathy.
4. Gustatory sweating
Profuse sweating of face during eating
5. Neurogenic bladder
Gradual loss of ability to void urine is the clinical hallmark. Diagnostic confirmation is
done by cystometric abnormality and residual volume. Chronic retention may lead to
repeated infection and renal failure.
6. Impaired cardiovascular reflexes
Orthostatic hypotension and persistent tachycardia result from autonomic neuropathy
affecting cardiovascular reflexes.
P-B M-7 L-20 Evaluation of Diabetic Neuropathy
Evaluation of Diabetic neuropathy

• Up to 50% of diabetic polyneuropathy may be asymptomatic.
• Systematic assessment of neuropathic symptoms and signs include:
o Thorough neurological examination
o Exclusion of confounding disorders
136
Neurological Examination /Test
• Orientation to time, place and person.
• Recent and remote memories.
Evaluation of higher • Attention span and concentration

instigative function • Language (e.g.; naming objects, repeating phrases, spon-
taneous speech).
• Fund of knowledge (e.g. awareness to current events, past
history, vocabulary)
• For 1st Cranial nerve (e.g. smell tests).
• For 2nd Cranial nerve (e.g. visual acuity, visual field, fundi
tests).
• For 5th Cranial nerve (e.g. facial sensation, corneal
reflexes test).
• For 7th Cranial nerve (e.g. facial symmetry, strength test).
Cranial Nerve
• For 8th Cranial nerve (e.g. hearings with tuning fork, whis-
Examination
pered voice and/or finger rub tests).
• For 9th Cranial nerve (e.g. spontaneous or reflex palatal
movement test).
• For 10th Cranial nerve (e.g. autonomic neuropathy tests).
• For 11th Cranial nerve (e.g. shoulder shrug strength test).
• For 12th Cranial nerve (e.g. tongue protrusion test).
Examination of
e.g. by touch, pin, vibration, proprioception tests.
sensation
Examination of deep in limbs with notation of pathological reflex. e.g. Babinski
tendon reflexes sign
e.g. finger/nose, heel/knee/shin, rapid alternating movement
Test of coordination in limbs .sign
Exclusion of confounding disorders:

1. Lumbar root disease
2. Peripheral vascular disease
3. Non-diabetic neuropathies – may be present in 10%diabetics
137
Autonomic nerve function tests
1. Resting tachycardia > 100/minute.
2. Postural drop of systolic blood pressure > 20mmHg (normally drop by <10mmHg).
3. Slowing of heart rate by <10/minute during deep breathing (normally heart rate falls
by>15/minute).
Special nerve function tests

1. Nerve action potential amplitude measurement represents total number of active
fibres.
2. Motor and sensory nerve conduction study reflects functional status of large,
myelinated fibres.
3. EMG done on intrinsic foot muscle may reveal partial degeneration as an early sign
of diabetic neuropathy.
4. Electrodiagnostic studies are usually done on ulnar and/ or median nerve (upper
limb) and peroneal nerve (lower limb) for motor function; ulnar and/ or median nerve
(upper limb) and medial plantar/ sural nerve (lower limb) for sensory functions.
5. Non-invasive, reproducible, and highly sensitive vibration thresholds are measured
by biothesiometer.
P-B M-7 L-21 Treatment of Somatic Neuropathy
Treatment of Painful Diabetic Peripheral Neuropathy

• Metabolic control: Optimum glycemic control.
• For burning pain: Antidepressants e.g. duloxetine, tricyclic anti-depressants etc. or
anticonvulsants e.g. gabapentin, pregabalin, or topical capsaicin etc. are used.
• For lancinating pain: Anticonvulsants e.g. carbamazepine, phenytoin or valproate are
used.
• For painful cramps: Quinine sulfate.
• Aldose reductase inhibitors may be used.
• Other contributing factors e.g. alcohol. cord lesions, vitamin deficiency, renal failure
etc. should be addressed.
138
P-B M-7 L-22 Treatment of Autonomic Neuropathy
Treatment of Autonomic Neuropathy

• Metabolic control: Good metabolic control may halt its progression.
• For gastroparesis: Erythromycin, metoclopramide, domperidone.
• For diarrhoea: antibiotics, loperamide.
• For impotence: PDES inhibitors.
• For neurogenic bladder: intermittent catheterization, surgery, drug (rarely).
• For orthostatic hypotension: midodrine, mineralocorticoids, elastic stockings, fluid
and salt intake, positional adjustments etc.
• Supportive measurese.g. physiotherapy.
P-B M-7 L-23 Decision making path of DN
Decision making path of Diabetic Neuropathy Management (5 steps)
Decision making path of Diabetic Neuropathy Management

• In T2DM at diagnosis and then once a
Detailed neurological year.
Step 1 examination in diabetic • In T1DM at diagnosis and after 5 years
person (Schedule) or earlier.
(When no neuropathy is documented)
Clinical examinations Monofilament,

Step 2 Screening tests pin-prick, vibration, postural hypotension
etc.
Step 3 Evidence of neuropathy With classification
a. Establish and maintain

• HbA1c <7%,
Step 4 Care strategies • Maintain BP<140/80 mm of Hg
Establish joint care if the neuropathy is

Step 5 Referral to neurologist
difficult to manage
139
There are 22 Lessons in this module 7. I understand the following points:

1. The micro-vascular complications of diabetes mellitus and their pathogenesis.
2. How to detect and manage various types of diabetic retinopathies.
3. How to detect and mange diabetic nephropathy.
4. How to detect and manage various types of diabetic neuropathies.
Further reading
Flyvbjerg & Barry J Goldstein, Wiley-Blackwell,2010
2. Davidson’s Diabetes Mellitus- Diagnosis & Treatment, 5th edition, edited by
A P Harme
l& R Mathur, Saunders,2004.
3. ClinicalDiabetes-TranslatingResearchintoPractice,1stedition, VA Fonseca,
Saunders,2006.
5. Global Guideline for Type2 Diabetes, Clinical Guidelines Task Force, IDF
(International Diabetes Federation),2012.
6. Evidence-Based Guideline for the Management of High Blood Pressure in Adults,
Report from the Panel Members Appointed to the Eight Joint National Committee
(JNC 8) 2013.
7. Guideline on the Treatment of Blood cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults, a Report of the ACC (American college of Cardiology)/
AHM (American Heart Association) Task Force on Practice Guidelines, 2013.
140
Retinopathy
Hypertension
Neuropathy
Nephropathy
CAD
PVD
Dyslipidaemia
Hypoglycaemia
HHS
Skin Disease
Gastro Complications
Foot Complications
Stroke
Phase-C
Module-8: Macrovascular Complications of

Diabetes Mellitus
Module-9: Diabetes Mellitus in Young and Older People
Module- 10 : Diabetes Mellitus in Special Situations
141
Module-8
Macrovascular Complications of
Diabetes Mellitus
142
P-C M-8 L-1 Objective
Objective
• To enumerate the macro-vascular complications of diabetes mellitus and discuss

their pathogenesis.
• To discuss on management of hypertension and dyslipidemia of a diabetic person.
• To perform clinical examinations of foot to detect ‘high risk foot’ and advice
diabetics for appropriate foot care practice.
P-C M-8 L-2 Introduction
Macroangiopathies
Diabetes mellitus is a disease associated with several macro-vascular complications

in the heart, brain and periphery (lower limb). The pathology that sets in such compli-
cations are called Macroangiopathy.
According to site of involvement there are three types of macroangiopathies.

• Coronary artery disease (CAD)-in the heart
• Cerebrovascular disease (CVD) – in the brain
• Peripheral vascular disease (PVD) – in the lower limb
Macroangiopathy
CAD CVD PVD
143
1. Coronary artery disease is the commonest cause of death in persons with
diabetes.
2. Stroke (cerebrovascular disease) is the second most common macro-vascular
problem in diabetes. Both of the above are also important causes of premature
mortality in diabetes.
3. Peripheral vascular disease (PVD) affecting the large arteries particularly of the
lower limbs are also common in diabetes. It adds considerably to the morbidity
related to foot problems leading to lower extremity amputations.
Macro-vascular complications of diabetes mellitus
Problems Prevalence
Stroke 6 Times
Blindness 25 Times
Heart Attack (MI) 2-3 Times
Kidney Failure 5 Times
Lower Limb Amputation 20 Times
144
P-C M-8 L-3 Factors affecting Macroangiopathy
Factors affecting Macroangiopathy
Duration of diabetes: Like microangiopathy, macroangiopathies of diabetes also

increases with duration of diabetes. T2DM people often present with macroangiopathy.
Status of glycemic control (blood glucose or HbA1c): strongly related to both micro
and macroangiopathies of diabetes.
3. Other factors
• Hypertension and dyslipidemia are the two very important modifiable factors in the
development of macroangiopathies.
• Smoking, obesity and lack of exercise are risk factors for coronary artery diseases.
• Genetic susceptibility to certain complications may be present.
• Age may be related to some complications.
• Insulin resistance is an independent risk factor.
All these factors should be taken into account during prevention and treatment of
complications.
145
P-C M-8 L-4 Mechanism of Macroangiopathy
• Atherosclerosis is the fundamental mechanism in development of macrovascular

disease.
• The blood vessels become thick, hard and less elastic. This makes it difficult for the
blood to flow through.
• People with diabetes have atherogenic dyslipidemia.
• High blood glucose affects the RBCs and makes them less pliable and may produce
hypoxemia.
• There is increase in the factors that favour blood clotting, damage, and change in
vascular endothelial lining, increased platelet stickiness etc.
• Atherosclerosis is several-fold more frequent in persons with diabetes. In diabetic
people atheromatous lesions are more severe and widespread.
• Insulin resistance probably plays an important role.
Findings during histopathology
Duration of diabetes: Like microangiopathy, macroangiopathies of diabetes also

increases with duration of diabetes. T2DM people often present with macroangiopathy.
A. Tear in the arterial wall

B. Macrophage cells
C. Cholesterol deposit
D. Red Blood Cells
E. Macrophage Foam cells
F. Fat cells
A. Tear in the arterial wall

B. Macrophage cells
C. Cholesterol deposit
D. Red Blood Cells
E. Macrophage Foam cells
F. Fat cells
146
P-C M-8 L-5 Hypertension
High blood pressure causes damage to large and small blood vessels in the
body. The higher the blood pressure the greater is the risk. The adverse
effect of hypertension mainly involves the blood vessels of heart, brain,
eyes and kidneys.
Changes in blood vessels due to hypertension
• In larger arteries the internal elastic lamina is thickened, smooth muscle is hypertro
phied, and fibrous tissue is deposited.
• In smaller arteries hyaline arteriosclerosis occurs in the wall, the lumen narrows, and
aneurysm may develop.
Some key points on hypertension in diabetes mellitus

• Hypertension contributes to the development and progression of chronic complica
tions of diabetes. In patients with type1 diabetes, persistent hypertension is often a
manifestation of diabetic nephropathy. In type2 diabetes, hypertension is often a part of
metabolic syndrome.
• Depending on the severity of hypertension, the optic fundi reveal a series of changes
(hypertensive retinopathy). Hypertension is also associated with central retinal vein
thrombosis. Hypertension accelerates the progression as well as increases the severity
of existing diabetic retinopathy.
• Hypertension may cause proteinuria and progressive renal failure by damaging the
renal vasculature. Diabetics are already at risk of kidney disease and added
hypertension increases the risk of kidney disease several folds.
Target organ damage (TOD) in hypertension
Organ Damage
Heart LVH, ML, angina, heart failure
Brain Stroke, TIA
Kidney CKD
Limb PVD
Eye Retinopathy
147
Target of blood pressure in diabetes
Many prospective studies with hypertensive diabetic persons have documented that
reduction of blood pressure is the single most important factor that reduces both renal
disease progression and cardiovascular events.
On the basis of those evidence now it is advised to lower the blood pressure to <140/80
mmHg, in all individuals, specially in patients with diabetes, chronic kidney disease or
target organ damage (TOD) due to hypertension.
Target of blood pressure
<140/80 mm of Hg
P-C M-8 L-6 Antihypertensive drugs
Group Drugs
Diuretics Hydrochlorothiazide, Chlorthalidone,
Indapamide
Angiotensin converting enzyme inhibitors Captopril, Enalapril, Lisinopril, Ramipril,
(ACEI) Perindopril
Angiotensin II receptor blockers (ARB) Losartan, Valsartan, Candesartan,
Irbesartan, Olmesartan, Telmisartan
Calcium channel blockers (CCB) Amlodipine, Lercanidipine, Lacidipine,
Nifedipine, Cilnidipine, Diltiazem,Verapamil
Beta adrenergic receptor blockers (BB) Atenolol, Metoprolol, Bisoprolol, Carvedilol
(BB+AB), Labetolol (BB+AB)
Alpha adrenergic receptor blockers (AB) Prazosin, Terazosin
Others Alpha methyldopa, Hydralazine, Eplerenon,

Aliskiren, Clonidine
148
Hypertension: decision making
P-C M-8 L-7 Hypertension treatment in DM
Treatment of hypertension in diabetes
Blood pressure should be measured at the initial visit and subsequently at every
follow-up visit.
At initiation of therapy usually a single drug is used but if B.P >160/100 mmHg two
drug regimen may be considered.
Follow-up monthly or more frequently to adjust medications; then at every follow-up

visit.
Drug Therapy:
• Antihypertensive regimens should include ACE inhibitors (ACEI) or angiotensin II
receptor blockers (ARB) in order to provide maximum cardio- and renoprotection in
these patients. But these two must not be combined.
• In virtually all patients with diabetes, combination of antihypertensive medications
may be needed to achieve the desired blood pressure target.
• At least one drug is to be given at bed-time.
• Glycemic and lipid control must be ensured.
149
Non-pharmacological interventions
• Weight loss for obese
• Regular exercise
• Medical nutrition therapy-plenty of vegetables and fruits, reduced total and
saturated fat
• Restriction of salt intake (<6 g/day)
• Limitation alcohol
Pharmacological interventions
Pharmacological interventions can be made with any of the following drug(s) accord-
ing to clinical situation. For dosage schedule follow standard text books.
P-C M-8 L-8 Dyslipidemia
• Dyslipidemia is defined as an abnormal level of one or more blood lipids-total cho

lesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and/ or
triglyceride (TG).
• There is strong evidence that elevated LDL and decreased HDL levels directly con
tribute to the formation of atherosclerotic plaques and in turn increase the patient’s
risk of cardiovascular disease.
• Though the concentration of total and LDL cholesterol in type2 diabetic patients is
usually not significantly different from non-diabetic individuals, the diabetics may
have elevated levels of non-HDL cholesterol (LDL and VLDL).
• However, type2 diabetic patients typically have a preponderance of small and dense
LDL particles, which possibly increase atherogenicity even if the absolute
concentration of cholesterol is not significantly increased.
Key features of diabetic dyslipidemia

• Hypertriglyceridemia
• A reduction in high-density lipoprotein cholesterol (HDL)
• A rise in small dense low-density lipoprotein cholesterol (LDL)
150
Apoprotein Cholesterol
Phospholipids
The main lipids in blood are carried in lipoproteins, which are globular packages that
also contain apoproteins and phospholipids.
• Cholesterol is an essential element of all animal cell

membranes and forms the backbone of steroid hormones
and bile acids.
Cholesterol • Although dietary cholesterol found in foods of animal origin
contributes to the plasma cholesterol level, endogenous
production is believed to account for most plasma
cholesterol.
• Triglycerides are simple lipids derived from fatty acids.
Vegetable oils, dairy products and animal fast contain
triglycerides.
Triglycerides • VLDL, a precursor of LDL, is involved in the transportation
of endogenous triglyceride from the liver to the peripheral
tissues.
• Chylomicron transports triglyceride from the gut to the
peripheral tissues.
• The major production of HDL occurs in the liver.
• Studies have reported that the HDL has a closer inverse
association with atherosclerosis. HDL shows an inverse
relationship with plasma LDL and triglyceride levels.
High-density
• Insulin treatment in type1 DM restores HDL to normal
lipoprotein (HDL)
range.
• In type 2 DM, HDL concentration is favourably associated
with female sex, weight loss, cessation of smoking, exercise,
and low intake of alcohol.
• The rate of LDL secretion from the liver is influenced by
Low-density diet, insulin, degree of adiposity etc; therefore, a wide variabili-
lipoprotein (LDL) ty in its level is common.
• High level of plasma LDL has been shown to be associated
with atherosclerosis and macro-vascular complications.
151
Target of blood lipids
Target of blood lipids is set to protect cardiovascular risk. It is dependent on:
• Presence of cardiovascular disease, e.g. coronary artery disease (CAD) or
equivalent conditions
• Diabetes mellitus (is considered as a CAD risk equivalent)
• Number of CVD risk factors present
Target of blood lipids for people with diabetes mellitus

No definite target is recommended
1. LDL cholesterol
<70 mg/dl – probably safe
>190 mg/dl – very high
<150 mg/dl
2. Triglyceride
>40 mg/dl (in male), >50 mg/dl (in female)
3. HDL cholesterol
P-C M-8 L-9 Dyslipidema Management
Screening for dyslipidemia

Studies have shown that correction of dyslipidemia very effectively helps to reduce the
risk of developing CVD in persons with diabetes. A lipid profile examination at baseline
and annually thereafter is therefore recommended in all adults with diabetes.
Treatment strategy of dyslipidemia in diabetes

• All intentions of management of dyslipidemia are aiming at reduction of ASCVD
(atherosclerotic cardiovascular disease). Now there is no recommendation for or
against any specific LDL-c or non-HDL-c targets.
• Statin has taken over the center stage because of its overwhelming cardiovascular
benefit.
Four major statin benefit groups:

1. Clinical ASCV
2. Primary elevation of LDL-c >190 mg/dl
3. Without ASCVD, with DM, LDL-c 70-189 mg/dl and age 40-75 yrs
4. Without ASCVD and DM, LDL-c 70-189 mg/dl and 10-yr ASCVD risk >7.5% (estimated
by risk calculator utilizing age, gender, total cholesterol, HDL-c, SBP, BP treatment, DM,
smoking)
152
Other indications for lipid treatment:
• Primary LDL-c >160 mg/dl
• Genetic dyslipidemias
• Family H/O premature ASCVD
• Elevated lifetime risk of ASCVD
Non-pharmacological interventions
• Medical nutrition therapy-plenty of vegetables and fruits; reduced total fat, saturated
fat (<7%) and dietary cholesterol (<200 mg/day)
• Weight loss for obese
• Regular exercise
• Limitation of alcohol
Pharmacological interventions
• Rosuvastatin 5-20 mg (upto 40 mg), or atorvastatin 10-40 mg (upto 80 mg) per day, or
equivalent doses of other statins are preferred according to risk level.
• In case of inadequate response or intolerance to statin, non-statin drugs, eg ezetimibe
or PCSK9-inhibitor may be added.
• TG >500 mg/dl is taken as very high. But realistic risk of pancreatitis is high at TG level
of >1000 mg/dl. TG lowering drug, eg fibrates, fish oil or nicotinic acid may be consid
ered if TG is >500 mg/dl. Statin should still be considered if the individual falls in one of
four statin benefit groups.
Groups Drugs Remarks

Statin (inhibits HMG-CoA a. Atorvastatin a. Lowers LDL
reductase activity) b. Fluvastatin b. Lowers triglyceride
c. Rosuvastatin c. Raises HDL
d. Pitavastatin
e. Simvastatin
Fibrate (stimulates a. Fenofibrate a. Lowers triglyceride

lipoprotein lipase activity; b. Gemfibrozil b. Raises HDL
increases VLDL
breakdown)
Nicotine acid (inhibits a. Nicotinic acid a. Lowers LDL

production of VLDL) b. Lowers triglyceride
c. Raises HDL
153
Cholestyramine (prevents a. Cholestyramine a. Lowers LDL
intestinal absorption of
cholesterol)
Ezetimibe (prevents a. Ezetimibe a. Lowers LDL

intestinal absorption of
cholesterol)
Fish oil (inhibits production a. Contains omega-3 fatty a. Lowers triglyceride

of VLDL) acids-eicosapentaenoic b. Raises HDL
acid and docosahexaenoic
acid
PCSK9-inhibitor (inhibits a. Evolocumab Lowers LDL

enzyme PCSK9) b. Alirocumab
P-C M-8 L-10 Aspirin use in diabetes
Aspirin use in diabetes
• Aspirin (75-150 mg/day) is to be used as secondary prevention strategy of CVD in

those with history of CVD.
• Aspirin (75-150 mg/day) is to be used as primary prevention of CVD in diabetics
with age >50 years, with hypertension, dyslipidemia, family history of CVD,
albuminuria, or smoking.
• It can also be considered in age group less than the above in presence of multiple
cardiovascular risk factors.
• Clopidogrel may be an alternative.
154
P-C M-8 L-11 Diabetic foot
Diabetic Foot
There are several reasons why foot of a diabetic person is vulnerable to lesion.
These include:
• Loss of sensation (neuropathy)
• Poor circulation (peripheral vascular disease)
• Higher likelihood of developing infections
Diabetic foot ulcers are the most common cause for prolonged hospitalization.
Lifetime risk of foot ulcer in diabetes is about 25%. Diabetes is the most important
cause of non-traumatic foot amputations; 50% of these patients have diabetes. After
amputation mortality rate reaches 40-80%.
Foot lesions in diabetes
Wagner’s grading of diabetic lesions

0 No ulcer but high risk foot
1 Superficial ulcer
2 Deep ulcer but no bony involvement, no abscess
3 Deep ulcer with abscess or bony involvement
4 Localized gangrene (at toe, heel)
5 Gangrene of whole foot
155
Wagner’s grading of diabetic lesions
Grade Description of lesion Example
0 No ulcer but high risk foot
1 Superficial ulcer
2 Deep ulcer but no bony involvement, no abscess
3 Deep ulcer with abscess or bony involvement
4 Localized gangrene (at toe, heel)
5 Gangrene of whole foot
Pathway of amputation
156
P-C M-8 L-12 High Risk Foot
A foot is labeled as ‘High risk’ if one or more of the 6 factors is/are present:
High Risk Foot

1 Loss of protective sensation
2 Absent pedal pulses
3 Severe foot deformity
4 Limited joint mobility
5 History of foot ulcer
6 Previous amputation
Screening for high-risk foot in diabetic person
Screening for high risk foot should be done at initial visit and at least yearly thereafter.
Follow-up of high risk foot should be done every 3-6 months.
Clinical assessment of foot

• Previous history of ulcer or amputation.
• Presence of thick nails, limited joint mobility and/ or bone deformity.
• Evidence of infection or increased pressure e.g. erythema, heat, callus formation,
haemorrhage under a callus.
• Peripheral vascular disease by examining peripheral pulses and by Doppler test
(ABI-Ankle-Brachial Index).
• Impairment of fine t ouch using Semmes-Weinstein nylon monofilament.
• Impaired thermal sensation using hot and cold test tubes separately.
• Raised vibration perception threshold using biothesiometer or graduated tuning fork.
157
P-C M-8 L-13 Foot Care Education for Diabetics
How to avoid heat injury to the foot?

Because of the associated nerve damage, a person with diabetes cannot sense tempera-
ture changes. So to avoid heat injury, the following precautions must be made known to
them:
• Do not have very hot baths.
• Avoid sitting too close to the heater or fire.
• Do not use hot fomentations.
• Avoid hot water bottles or electric blankets in the bed at night.
• Avoid all possible injuries.
How to inspect feet?

• Inspect feet regularly (preferably daily)-the toes, between the toes and the sole, and
look and feed for breaks in the skin, cuts, scratches, bruises, blisters, sores and discol
oration.
• Use a mirror or friend/ relative to aid better viewing.
How to cut nails?

• Cut nails after a bath, when these are soft and pliable.
• Cut nails straight, not too deep on the sides.
• Do not use sharp instrument to clean under the nail, or in the grooves.
• In case of pain or difficulty in cutting, consult nurse or doctor.
158
P-C M-8 L-14 How to Choose Footwear for a Person with Diabetes?
Shoes must provide proper support to the foot. Following points should be considered:
Components Recommendations
Shoes must be of the correct shape and size for the feet. It is
important to draw the outline of the feet by placing them on
Shape and size paper. Then to cut this outline and carry it when buying shoes.
The cut paper must fit the inside of the shoe properly without
crimping or folding anywhere.
This would be the correct and comfortable shoe size.
Flat shoes should be chosen. Thick, sturdy soles protect the

Heel & sole
feet from sharp objects.
Toe box Rounded wide toe box gives more space to the feet.
Material Leather shoes help the feet breathe freely.
Shopping for shoes should be always in the evening when the

Shopping
feet are the largest.
Woolen/cotton socks are to be used. Knee-high socks, or
Socks socks with tight tops or rough seams should be avoided.
Check the size of the shoes wearing the thickest socks.
Slippers and sandals do not provide adequate support to the
Slippers and sandals feet and should be avoided for full-day-wear. They should be
used only for short periods like night-wear.
159
P-C M-8 L-15 Oral and Skin Care
Besides foot lesions, elevated blood glucose increases the risk of dry mouth, gingivitis
and periodontitis, dental caries, tooth loss, oral infections, etc. Diabetics are also prone to
develop various dermatological problems. So, it is very important to maintain adequate
personal hygiene, regular dental check-up etc.
Other complications and comorbidities

1. Diabetes may affect skin, musculo-skeletal system and other tissues to cause a
number of lesions.
2. Diabetic individuals are very much prone to wide range of infections. Sometimes
these are very difficult to treat.
3. Diabetic patients may have some comorbid conditions, e.g. fatty liver, depression and
cognitive impairment, cancer etc.
160
P-C M-8 L-16 Summary
There are 14 Lessons in this module. I understand the following points:

• The macro-vascular complications of diabetes mellitus and their pathogenesis.
• How to management of hypertension and dyslipidemia of a diabetic person.
• How to perform clinical examinations of foot to detect ‘high risk foot’ and advice
diabetics for appropriate foot care practice.
Further Reading
1. Text Book of Diabetes, 4th edition, edited by Richard I G Holt, Clive 5 Cockram, Allan
2. Davidson’s Diabetes Mellitus-Diagnosis & Treatment, 5th edition, edited by A P
Harmel& R Mathur, Saunders, 2004.
3. Clinical Diabetes- Translating Research into Practice, 1st edition, V A Fonseca,
Saunders, 2006.
5. Global Guideline of Type2 Diabetes, Clinical Guidelines Task Force, IDF (International
6. The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation & Federation), 2012
Evaluation & Treatment of High Blood Pressure (JNC 7), 2004.
Report from the Panel Members Appointed to the Eighth Joint National Committee
(JNC 8), 2013.
9. Third Report of the NCEP (National Cholesterol Education Program) Expert Panel on
Detection, Evaluation & Treatment of High Blood Cholesterol in Adults (Adult Treat
ment panel III),
10. 2001 (Revised in 2004).
11. Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic
Cardiovascular Risk in Adults, a Report of the ACC (American College of Cardiology)/
AHA
12. (American Heart Association) Task Force on Practice Guidelines, 2013.
161
Module-9
Diabetes Mellitus in
Young and Older People
162
Objective
• To discuss the basic principles of management of diabetes mellitus in the young

population.
• To discuss the basic principles of management of diabetes mellitus in the older
people.
• To discuss the basic principles of management of diabetes mellitus during
pregnancy.
P-C M-9 L-2 DM in the Young
DM in children and adolescents

Diabetes mellitus in childhood and adolescence is most often type1 diabetes. But they
have the chance of developing T2DM and other specific types of diabetes.
Now-a-days T2DM is developing in the young at a very high rate.
Diagnostic and management issues in this group of population is different from that of
adult.
T1DM
• Type1 diabetes is growing by 3% per year in children and adolescents, and by 5% per
year among pre-school children. Of these type1 diabetic children the highest number of
cases (26%) live in Europe. Finland, Sweden, Denmark,
• An estimated 1.1 million children and adolescents (aged under 20 years) have type 1
diabetes.
• Norway and the UK have higher incidence rates for type1 diabetes inchildren.
• Globally, there are close to 500,000 children under the age of 14 years with type1
diabet es. Every year, 79,000 children under the age of 14 years develop type1diabetes.
163
T2DM
• Type2 diabetes mellitus in children is relatively less common than in adult. But
now-a-days it is being reported more frequently and is associated with rising rate of
obesity among thechildren.
• Type2 diabetes was once seen as a disease of adults. Today, this type of diabetes is
growing at alarming rates in children and adolescents. In the USA, it is estimated that
type2 diabetes represents between 8 and 45% of new-onset diabetes cases in children
depending on geographic location. Over a 20-year period, type2 diabetes has doubled
in children in Japan, so that it is now more common than type1.
• Type2 diabetes in children is becoming a global public health issue with potentially
serious outcomes. Type2 diabetes affects children in both developed and developing
countries. Over half of children with diabetes develop complications within 15years
P-C M-9 L-3 Screening for Diabetes in Children
Screening for diabetes in children

Whom to screening for Diabetes among Children?
All types of DM Children with symptoms of diabetes.
Children with Risk factor(s) of DM
• Obesity (BMI > 85th percentile for age &sex.
• Family history ofT2DM
T2DM • Mother was DM/GDM during the child's gestation
• Ethnic susceptibility.
• Features of Insulin resistance: Example: acanthosis nigricans,
hypertension, dyslipidemia, polycystic ovarian syndrome
(PCOS), low birthweight.
164
Some points on screening for DM in children
• Diabetes in children usually presents with classical symptoms. Fasting blood

glucose (FBG) ora random blood sugar (RBS) are often suffice to level them as
diabetic. In case of suspicion of type 2 diabetes OGTT can be done.
• Children with obesity plus 2 other risk factor should be screened at the age 10 years
or at onset of puberty.
• If normal than once in every 3 years.
• In many tropical countries, including Bangladesh, there is a substantial number of

young lean diabetic cases with or without pancreatic calcification that are assigned
as specific type diabetes (FCPD); previously they were called 'Malnutrition Related
Diabetes Mellitus' (MRDM).
P-C M-9 L-4 Principles of Diabetes Management in Childhood
Principles of diabetes management in childhood

Management of the diabetes in children needs special skill in this field. Three fundamen-
tal components/domines of DM management in children
• Pharmacotherapy.
• Diabetes Education(DE)
• Medical Nutrition Therapy (MNT)
They do not differ much from those of adults. However, they mostly need insulin because
they are either of type1 DM or of other types with severe insulin deficiency.
Targets of diabetes management in the young (based on ISPAD guideline) – targets are
of three domains:
1. Glycemic Targets,
2. Targets of Growth and
3. Targets of Diabetes Education.
165
1. Glycemic Targets
Pre-meal
Post-meal Bed time Hypoglycemia HbA1c%
(Fasting)
5.0 - 8.0 5.0 - 10.0 6.7 - 10.0 No < 7.5
Targets of 2. Growth and 3. Diabetic Education (DE)
2. Growth Within +/- 2.5 SD of Growth Chart
Teaching, training, and empowerment to take part in treatment

3. DE
such as SMBG & insulin administration.
P-C M-9 L-5 MNT and Drugs DM in Children
Medical nutrition therapy (MNT) and Drugs of DM in Children

Medical nutrition therapy (MNT) of DM in Children
MNT
• A meal plan is based on the individual’s usual food intake, insulin therapy, exercise
patterns etc.
• Timing and amount of food will depend on type of insulin, physical activity, lifestyle
and results of blood glucose monitoring.
• All children with diabetes should be referred to a dietitian for counseling at

diagno sis of diabetes
• and also subsequently if they have problem with their diet adjustment. Age-specific
calorie calculating charts are available for measuring diet allowance.
Drugs of DM in Children
166
Drugs of DM in children on the basis of type & age
Type DM (Age) Drug

T1DM (any age) Insulin only
T2DM (< 10 years) Insulin only
T2DM (10-18 years) Insulin or metformin
After 18 years of age, all anti-diabetic agents can be prescribed.
P-C M-9 L-6 Diabetes Education for Yong Diabetic
Diabetes education
• Diabetes education is fundamental in treatment of young diabetics. Diabetes
education needs to be a continuous process and repeated for it to beeffective.
• They are to be trained to develop skill in all aspects of diabetes, especially insulin
injection technique, dietary practice, home monitoring of blood glucose and foot care
etc.
• Providing emotional support is veryimportant.
• Diabetes education according to agegroup
1. Infants and toddlers: They are totally dependent on parents and care providers for
injections, food and monitoring. Advised to stop or minimize erratic eating and activity.
Education on prevention, recognition and management of acute complications, especially
hypoglycemia, because it is very common complication in this age group.
2. School going children: Training on insulin injections ,blood glucose monitoring ,

recognizing hypoglycemic symptoms and understanding self-management.Trained to
adapt to school programs, school meals, exercise and sports.Teacher/ school authority
should be involved. The parents are advised on the gradual development of the child’s
independence.
3. Adolescents: Independent, responsible self-management appropriate to the level of

maturity and understanding should be promoted. Strategies to manage transition to
adulthood and progressive hand-over of responsibility are to be developed.
167
Sports and exercise of young diabetics.
• Children with type1 diabetes with good blood glucose control can do all levels of
exer cise, including leisure activities, recreational sports, and competitive professional
performance.
• Exercise is more important for young type2 diabetic, specially who are obese. The
emphasis must be on adjusting the therapeutic regimen with the level of exercise and
diet and avoiding hypoglycemia.
• Extra attention and support of parents, teachers, school attendants and trainers may be
necessary.
Sport and exercise according to age group
3-5 years may take part in free play, walking, running etc.
may start learning to play team sports such as football,
6-9 years
cricket etc.
may be able to take part in all complex sports, like basketball,
above 10 years
football, tennis, hockey etc.
In case of adolescents, hormonal changes can contribute to the difficulty in controlling
blood glucose levels. So extra care is required for exercise in the age group.
P-C M-9 L-7 Hypertension and Dyslipidemia in Children
Hypertension in the young with DM

• Hypertension in childhood is defined as systolic or diastolic blood pressure >95th
percentile forage, sex and height. ‘High-normal’ blood pressure is defined as systolic or
diastolic blood pressure >90th but <95th percentile for age, sex and height.
• Treatment of high-normal blood pressure is given through lifestyle measures. If target
blood pressure is not reached within 3-6 months, pharmacologic treatment should be
initiated.
• Drug treatment should be started as soon as hypertension is confirmed. ACE inhibitor
is the preferred agent. The goal of treatment is a blood pressure consistently <90th
percentile for age, sex and height.
Dyslipidemia in the young with DM

1. A fasting lipid profile should be performed in children >10 years of age soon after
diagnosis of DM (after diabetes control).
2. If lipid is abnormal, annual monitoring is advised.
3. If in acceptable limit (LDL <100 mg/dl), 3-5 yearly monitoring is recommended.
4. After the age of 10 years, statin is recommended in patients who do not reach target
with lifestyle changes. The goal of therapy is an LDL <100mg/dl.
168
P-C M-9 L-8 DM in the Older People
DM in the older people

The definition of old age is arbitrary. 60 years may be taken as beginning of old age.
People over 60 years of age form about 15% of total population globally.
Among total diabetics of the world, 60-year group constitutes about 35%. And among
total population over 65 years of age, 25% are diabetics.
So they are putting a great impact on general as well as in diabetic populations.
Health Status of Older people

Apparently Good
Poor Health
Health
Life expectancy More Intermediate Less
Physical/mental fitness More Intermediate Less
Independence More Intermediate Less
Management Less relaxed Intermediate More relaxed
• Management of DM in old people depends on their health status determined by life expectancy,
physical and mental fitness and intendance.
• Those in good health-all general recommendations apply. Intermediate/poor health-testing

should be done when clinically indicated, by simpler procedures, e.g. RPG, FPG orHbA1c.
Treatment goals are set according to health status

Pre-meals (Fasting)
Health Status
(mmol/L)
Good 7.2 < 7.5
Intermediate 8.3 < 8.0
Poor 10.0 < 8.5
Contribution of PPBG at all HbA1c levels is higher compared to FBG in older people.
169
P-C M-9 L-9 MNT and Physical Activity in Older People
Points to consider for MNT

1. Swallowing or eating difficulties may be present.
2. Adequate fluid is to be ensured to avoid dehydration.
3. Malnutrition or weight loss should be taken care.
4. Tube feeding or parenteral nutrition may be needed in some.
Points to consider for physical activity

1. Older people are encouraged to be active as condition allows, from regular
exercise to simple home-based mobility.
2. Risk assessment should be done before recommending activity.
3. Risk of injury with fall and hypoglycemia is to be considered.
4. Physical (physio)therapy may be needed for some.
P-C M-9 L-10 Drug Treatment of DM in Older People
Key points for drug treatment

1. ‘Start low, go slow’, applicable to most medications.
2. Agents which preferentially lower postprandial hyperglycemia may be more effective
in achieving glycemic goals without increasing the risk of fasting hypoglycemia.
3. Swallowing difficulty may limit oral drug intake.
4. Metformin is first-line therapy. Metformin may cause unintended weight loss and
higher gastrointestinal side-effects.
5. DPP-4 inhibitor/GLP-1 agonist may also be considered.
6. Glibenclamide has the highest risk of hypoglycemia; gliclazide has the lowest.
Glibenclamide should be avoided.
7. Glinides and AGI may be considered in postprandial hyperglycemia, Glinides are
also useful in erratic eating habits.
8. Insulin may provide anabolic benefit in frail ones. Long acting insulin analogue is
safe and efficacious in older people.
9. Rapid/short acting insulin targets post-prandial blood glucose better.
10. Visual, motor and cognitive impairments may hamper insulin injection. Insulin
pen devices can simplify administration.
11. Complex regimens should be avoided to reduce errors.
170
P-C M-9 L-11 Acute Emergencies and Co-Morbidities
Acute emergencies of DM in Older people

• Hypoglycemia and sick day management plan should be strengthened.
• Older people are more prone to hypoglycemia. BG <6.0 mmol/L is to be avoided.
• HbA1c <7.0% should be taken as warning of possible over treatment.
Causes of hypoglycemia in elderly people with DM

1. Polypharmacy
2. Erratic meals and unusual activity
3. Renal, hepatic impairment
4. Malabsorption, swallowing problems
5. Defective counter regulatory system, antecedent/unaware hypoglycemia
6. Congnitive impairment, less expression of symptoms,
Like hypoglycemia, timely recognition and management of hyperglycemic emergencies

(DKA, HHS) in older people must be ensured.
Co-morbidities of DM in Older people

• Several comorbid conditions are usually present in older people along with
complications of diabetes.
• There may be cognitive impairment, falls, pain, arthritis, fractures, hearing impairment,
functional disability, urinary incontinence, obesity, stroke, CHF, periodontal disease,
cancer, depression, hypertension, dyslipidemia etc. All these should be addressed as
171
P-C M-9 L-12 Hyperglycemia (DM) and Pregnancy
Hyperglycemia and DM
Hyperglycemia during Pregnancy may be one of the 2 types- a. GDM and b. pre-pregnancy
glucose intolerance/DM. Pregnancy with hyperglycemia is a high risk health status.
Care must be given with an aim to make pregnancy as safe as in a non-diabetic state for
both the expectant mother and the baby.
Such a goal is feasible if blood glucose can be maintained to a non-diabetic level through-
out the pregnancy.
Some key points

1. Diabetes in pregnancy has associations with acute as well as chronic maternal
and fetal complications.
2. Good diabetic control throughout pregnancy as well as improved neonatal
management has lead to a reduction in the incidence of morbidity and mortality
associated with pregnancy in diabetic women.
3. Spontaneous abortions and congenital anomalies are seen much less when good
diabetic control has been established prior to conception and maintained during
the first 6-8 weeks of pregnancy.
4. Multidisciplinary preconception care improves the outcome of pregnancy in terms
of both the mother and the baby.
172
P-C M-9 L-13 DM and Pregnancy: Forms & Problems
Two forms of diabetes during pregnancy:

1. Pre-pregnancy diabetes mellitus:
Woman is a known diabetic before she becomes pregnant.
2. Gestational diabetes mellitus (GDM):
Glucose intolerance is detected first time after the woman becomes pregnant.
Diabetes during pregnancy is mostly due to GDM. Recent global prevalence of hyperglyce-
mia in pregnancy (both pre-pregnancy and GDM) is about 17% of live births; 84% of those
are due to GDM.
Problems of pregnancy in diabetes in the mother:

1. Pregnancy loss- abortion/ intrauterine death
2. Pre-eclampsia, eclampsia, polyhydramnios.
3. Difficulty in diabetes control
4. Deterioration of pre-existing complications, e.g. retinopathy, nephropathy
Problems of pregnancy in diabetes in the baby:

1. Macrosomia [birth weight above 4500 grams (some prefer 4000 grams as cut-off), or
above 90th percentile for gestational age] caused by chronic maternal hyperglycemia
causing fetal hyper-insulinism that results in excessive fat deposition and
organomegaly. It affects 15-45% pregnancies.
2. Intra-uterine growth retardation. Neonatal hypoglycemia due to sudden withdrawal of
maternal glucose at birth in presence of fetal hyper-insulinism. It affects 25-40%
pregnancies.
3. Polycythemia and hyperbilirubinemia partly due to response to relative hypoxia in
utero.
4. Neonatal hypocalcemia due to functional hypoparathyroidism.
5. Respiratory distress syndrome due to delayed maturation of the enzyme machinery for
synthesis of lung phospholipids.
6. Congenital malformations (2-6 times higher than non-diabetic pregnancies; these are
much higher for some particular malformations), e.g. cardiac or renal anomaly, caudal
regression, CNS defects etc.
173
P-C M-9 L-14 Pre-Pregnancy Diabetes
Pre-pregnancy diabetes
Pregnancy in all women with known diabetes must be pre planned. Diabetic women of
child bearing age and desirous of pregnancy, must be thoroughly counseled.
Pre-conception counseling must include intensive education about:

1. Importance of tight glycemic control before and during pregnancy
2. Medical nutrition therapy, physical activity
3. Skill on insulin injection techniques, home monitoring of blood glucose
4. Need for close and regular follow-up.
Pre-conception treatment of DM
1. Oral anti-diabetic agents (also other non-insulin injectable agents) must be discontin
ued.
2. The women are managed with lifestyle modification and insulin (if necessary) to
achieve tight metabolic control, which is defined by HbA1c and blood glucose values.
3. At all times blood glucose should be within the target.
4. Pregnancy should be postponed until treated for complications of diabetes or any
associated illnesses prior to pregnancy.
P-C M-9 L-15 GDM and Its Screening
Gestational diabetes mellitus (GDM)
called GDM. Placental hormones are responsible for the development of GDM.
Risk Factor for GDM
• Previous history of GDM

• Age >25years
• Bad Obstetric History (BOH) eg delivered baby Large for Gestational Age - LGA
(>9lb/4 kg at term delivery) or Small for Gestational Age SGA (< 5.5lb/2.5 kg at term
delivery), abortion, stillbirth or difficulty to conceive
• Excessive weight gain during pregnancy
• Others: BMI >23 kg/m2, A1C ≥5.7%, IGT or IFG, physical inactivity, first degree rela
tive with DM, hypertension, HDL <35mg/dl, TG >250mg/dl, PCOS, acanthosis nigri
cans, history of CVD
174
Schedule of screening for GDM
1. At 1st prenatal visit: If there is one or more risk factors of DM (or Mother wants to
know her status).
2. During 24-28th weeks of gestation: In all pregnancies (Mandatory).
3. During 34-36th weeks of gestation: for negative cases during 24-28 weeks of
gestation and there is one or more risk factors of DM (Optional).
P-C M-9 L-16 Diagnosis of GDM
Diagnosis of GDM
OGTT with 75 gms of glucose drink and 3 sample (Fasting, 1 hour & 2 hour) glucose
assay is the standard test. One or more value above is cut off is considered positive.
Currently cases are either leveled as GDM or over DM as per cut off shown in the table
below. RBS and HbA1c are also used for diagnosis of GDM.
Diagnosis of GDM/overt DM (based on ADPSG, ADA & WHO criteria)

<5.1 mmol/L Normal GDM
FBG 5.1 - <7.0 mmol/L Overt DM
>7.0 mmol/L
<10.0 mmol/L Normal GDM
1 hr. PG (75 gm OGTT) >10.0 mmol/L No specific value Overt DM
<8.5 mmol/L NormaGDM

2 hr. PG (75 gm OGTT) 8.5 - <11.1 mmol/L Overt DM
>11.1 mmol/L
No specific value GDM
RBS (with symptomps of
>11.1 mmol/L Overt DM
hyperglycemia)
No specific value GDM

HbA1c% >6.5% Overt DM
175
P-C M-9 L-17 Targets and Check-up Schedule
Targets of diabetes management during pregnancy

Targets of diabetes management during pregnancy (based on ADA guideline)
Blood (plasma) glucose • Fasting/pre-meal <5.3 mmol/L

• 1 hour post-meal <7.8 mmol/L
Glycemic Targets • 2 hour post-meal <6.7 mmol/L
HbA1c < 6.0% (once in each trimester)
Hypoglycemia No
• Systolic 110 - 135 mm of Hg
Blood Pressure
• Diastolic <85 mm of Hg
10 - 15 kg( for person with normal

Weight gain
weight & single tone pregnancy)
Mother (& family member) Teaching, training & empower-

Diabetic Education ment to take part in management
(SMBG & insulin injection)
Check up schedule of diabetic pregnancy

(both pre-pregnancydiabetes and GDM)
Follow up at clinic once every two weeks up to 30th
gestational week and thereafter
once every week.
Treatment schedule Team care Office treatment should comprise
of a team of specialists
Diabetologists, obstetricians and
nutritionists.
• Retinal and renal assessment
1st visit
• Detailed ultrasound (anomaly
Important antenatal check-up in addition to scan) - 20th week Ultrasound
check-up SMBG audit monitoring of fetal growth and
amniotic fluid volume- 28th week
• Tests of fetal well-being - 38th
week. (Some of these are
repeated periodically)
176
P-C M-9 L-18 Lifestyle and Drugs Treatment
Lifestyle (MNT and Physical activity)

Calorie requirement Daily total calories intake is to be 30
kcal/kg of ideal body weight in first
trimester and 38 kcal/kg of ideal body
weight thereafter.
Calorie distribution Carbohydrate 50-60%, fat 30%, protein

10-20% (may be increased in exchange
of carbohydrate).
MNT
Nutrient supplements Adequate supplementation of iron, folic
acid and calcium.
Meal pan • Major Meals: Breakfast, lunch, dinner.

• Snacks: Mid-morning, mid-afternoon
and bedtime.
(Bedtime snack is essential to prevent
fasting ketonuria).
Moderate physical activity should be

Physical activity
encouraged
Drug therapy
Insulin is the only drug recommended for use in pregnancy
Insulin therapy should be instituted if dietary compliance fails to

maintain glycemic target or blood glucose is much higher.
In pre-pregnancy diabetes shift from OAD to insulin when preg-

nancy is planned.
Insulin is started at a dose of 0.2-0.5 u/kg day. Human short and

MNT
intermediate acting insulins, and insulin analogues [rapid acting
(aspart, lispro) and long acting (detemir)] are recommended
during pregnancy.
Dose requirement will show increasing trend with duration of

pregnancy, specially in mid-pregnancy. Multiple dose insulin
therapy can better attain target of blood glucose levels.
Physical activity SMBG is required to maintain tight glycemic control.
177
P-C M-9 L-19 SMBG is Required to Maintain Tight Glycemic Control
Drug therapy
Term vaginal delivery is feasible in most diabetic pregnancies by
Term vaginal meticulous control of diabetes modern obstetric technology,
delivery monitoring of fetal well-being (by studying fetal heart rate) and
lung maturity (by testing amniotic fluid).
Delivery may be considered earlier in presence of unfavorable

Delivery considered conditions, e.g. uncontrolled diabetes, hypertension, chronic
earlier diabetic complications, pre-eclampsia, foetal growth retardation,
etc.
Caesarean section is usually required if the foetal

Caesarean section
weight > 4.5 kg.
Diabetes management during labor and delivery

Blood glucose should be between 4.0-6.9 mmol/L in order to
prevent neonatal hypoglycemia. It is best achieved by continu-
During delivery ous glucose-insulin infusion, because it is essential to meet the
energy expenditure of active labour. Blood glucose should be
monitored hourly.
The infusion is stopped immediately after the delivery of the

baby. During this time regular insulin in small dose is given
After delivery before meals in pre-pregnancy diabetics; pre-pregnancy regular
schedule of insulin may be started when the condition is fully
stable.
In almost all GDM cases insulin is not at all required after deliv-
ery; they become euglycemic. There is about 65% chance of
developing GDM in subsequent pregnancy. In all GDM cases
After delivery GDM
OGTT should be done 6-12 weeks after delivery; if it is normal,
OGTT should be repeated every 3-year, as these group of individ-
uals are at high risk of future diabetes (50% in 10 years).
178
Hypoglycemia in Newborn
All newborns of diabetic mothers have risk to develop hypogly-
Risk
cemia
Blood glucose levels must be checked by heel prick within 30-60

Check up minutes of birth and continued at regular intervals until one is
sure that there is no risk for hypoglycemia.
Neonatal hypoglycemia is defined as blood glucose level less

Definition
than 40 mg/dl.
If the glucometer readings are between 25 and 40 mg/dl, 10-15

ml of 10% glucose is given orally; repeated if necessary and
feeding is started as soon as possible.
If the glucometer readings are less than 25 mg/dl, intravenous

10% dextrose at the rate of 6 mg/kg/minute is started. Bolus
Check up doses are to be avoided as this may stimulate the already
overactive pancreas to secrete more insulin and add to the
problem.
Blood glucose monitoring is continued until the danger of hypo-

glycemia is completely over, usually in 24 hours; sometimes it
may take 72 hours.
179
There are 18 Lessons in this module. I understand the following points:

• The basic principles of management of diabetes mellitus in the young population.
• The basic principles of management of diabetes mellitus in the older people.
• The basic principles of management of diabetes mellitus during pregnancy.
Further reading
1. Text Book of Diabetes, 4th edition, edited by Richard l G Holt, Clive S Cockram, Allan
Flyvbjerg & Barry J Goldstein, Wiley-Blackwell, 2010
2. Standards of Medical Care in Diabetes, ADA (American Diabetic Association), 2018.
3. Global IDF (International Diabetes Federation) /ISPAD (International Society for
Pediatric & Adolescent Diabetes) Guidline for Diabetes in Childhood & Adolescence,
2011.
4. Global Guideline for Managing Older people with Type 2 Diabetes, IDF (International
5. Diagnostic criteria & Classification of Hyperglycemia First detected in Pregnancy,
WHO (World Health Organization) 2013.
6. International Association of Diabetes & Pregnancy Study Groups Recommendations
on the
7. Diagnosis & Classification of Hyperglycemia in Pregnancy, Diabetes Care, volume 33,
number 3, 2010.
8. Diabetes and Pregnancy, an Endocrine Society Clinical Practice Guideline, 2013.
180
Module-10
Diabetes Mellitus
in Special Situations
181
• To enumerate the basic principles of management of diabetes mellitus during surgery.

• To highlight the special care during days of sickness.
• To focus on the special aspects of Ramadan fasting.
• To discuss on prevention of diabetes mellitus.
• To discuss on diagnosis and treatment tuberculosis in diabetic person.
P-C M-10 L-2 DM in Special Situations
Sicknesses like fever, vomiting and diarrhoea; fasting during Ramadan and surgery in a
diabetic person are considered as special situations in this chapter.
During these periods the routine day-to-day management of diabetes needs to

adjusted.
• Surgery in diabetic persons is associated with increased preoperative complications.
Surgery can be made safe with optimal care of diabetes.
• During sick days and Ramadan fasting control of diabetes needs special attention to
overcome the interruptions in lifestyle.
Sickness like fever,

Fasting during Ramadan Surgery
vomiting & diarrhoea
182
P-C M-10 L-3 Surgery and DM
Surgery in diabetic persons has associations with increased risk of per-operative and
post-operative complications compared to those in non-diabetic persons.
This is due to the involvement of their vital organs including the autonomic nervous
system in the course of the disease. With optimal care, a surgery can be safe in diabetics.
Necessary surgical procedures should not be avoided due to diabetes.
Necessary surgical procedures should not be avoided due to diabetes.
• Poor metabolic control results in acute metabolic complications by the surgical

stress which may endanger life.
• The infection, if develops, tends to become virulent; it further worsens the metabolic
stability, thus creates a vicious cycle.
• Hyperglycemia itself leads to impaired wound healing, deficient formation of
granulation tissue and thereby poor tensile strength of collagen. The fibroblast
formation takes longer time and there is a deficient capillary growth into the wound.
The chemotactic, phagocytic and bactericidal activity
• of the neutrophil is deficient. There is impaired humoral host defense mechanism
and abnormal complement function.
• Aim should be to have optimal control of diabetes in all diabetics undergoing
surgery. This may not be always feasible, especially in an emergency situation.
Factors to be considered during planning surgery
1. Type of diabetes mellitus

2. Treatment - diet, oral anti-diabetic drugs, insulin etc.
3. Metabolic status
4. Vascular status - mainly cardiac, also renal and cerebral
5. Neurological status - specially of autonomic nervous system
6. Type of surgery - Emergency or elective; minor or major procedure
7. Type of anesthesia
8. Post-operative oral intake
183
P-C M-10 L-4 General Principles of Management (Steps 1 & 2)
There are 5 steps of actions.

Steps of management for surgery for person with DM
Steps Actions
1 Pre operative assessment
2 Actions of Day prior to Surgery
3 Actions of Day of Surgery
4 Actions of During operation
5 Post-operative care
Step 1. Pre-operative assessment for surgery for person with DM
Steps Actions
Pre-operative assessment must be done in close consultation with
1
the physician, surgeon and anesthetist
It should include assessment of any diabetic complications or asso-
2 ciated conditions, which may increase surgical risk, e.g. cardiac
autonomic neuropathy.
Step 2. Actions of day prior to surgery for person with DM
Steps Actions
Long acting secretagogues and biguanides should be changed prior
1
to surgery.
For major surgeries, the patient may be kept nil per oral (NPO)
2 over-night prior to surgery; in patients with gastroparesis, the duration
of NPO should be around 10-12 hours.
184
P-C M-10 L-5 General Principles of Mnagement (Steps 3,4 & 5)
General principles of management (Step 3, 4 & 5)

Step 3, step 4 and step 5 are actions on day of surgery, action during surgery and post
operative care respectively.
Step 3. Actions of day of surgery for person with DM

1 Anti-diabetic medications are omitted on the morning of the operation.
2 Surgery should be scheduled as early as possible in the morning.
In all major surgeries glucose-insulin infusion should be started. The
unit of insulin to be added to 5 or 10% dextrose or dextrose saline
needs to be individualized and adjusted as per the results of the
3
glucometer readings. Blood glucose should be monitored
1 to 2 hourly; it should be in the range of 6.0-10.0 mmol/L. Glucose-
insulin-potassium infusion may be considered according to situations
During minor surgery glucose-insulin infusion may sometimes be
4
required in uncontrolled diabetes, but not in stable state.
Step 4 Actions of during operation for person with DM

The choice of the anaesthetic agent is best left to the anaesthetist;
1
there is no preferred choice of anaesthetic agent for diabetics
2 Cardiovascular status should be closely monitored during surgery.

The glucose-insulin administration is continued where it is required; it is
3
guided by blood glucose monitoring.
Step 5 Post-operative care for person with DM

The glucose-insulin administration is continued (where required) till the
1
patient is able to take oral, food.
At this time, if the blood glucose is not under fair control, short acting
2
insulin can be given in small doses.
Once patient is back on his routine diet and is stable, he can be

3
managed with the regimen he was on prior to surgery.
185
P-C M-10 L-6 Specific Strategies of Surgery with DM
Four different strategies are followed in 4 different type of situations as

described in the following table.
Specific strategies for
1 For minor surgery in well controlled DM
2 For major surgery (requiring over-night NPO)
3 For poorly controlled DM
4 For emergency surgery
Strategies for minor surgery in well controlled DM

Patient on short acting secretagogues and/or insulin should omit
1 breakfast and the morning dose. The drug(s) should be restarted once
patient is back on routine diet after operation.
Patient on long acting secretagogues should replace it with shorter
2
acting secretagogues at least 5 days prior to surgery.
3 Per-operative glucose-insulin drip is usually avoided.
For major surgery (requiring over-night NPO)

1 Diabetes should be controlled by insulin
2 Per-operative glucose-insulin drip is essential.
In the post-operative period, once diet is resumed, patients usually do
3
better with short acting insulin therapy.
Restarting of the patent's previous regimen can be done once the
4
patient is fully stable
186
P-C M-10 L-7 Strategies for Poorly Controlled DM and Emergency
Strategies for poorly controlled DM

1 FInsulin is used to control diabetes in all types of operation
2 Hospitalization of the patient at least 3 days before operation.
Short acting insulin is preferred; but this also depends on type of DM
3
and operation etc.
Per-operative glucose-insulin drip is required, especially in major
4
surgery.
Strategies for emergency surgery

1 Patient is hospitalized.
Insulin infusion is started and frequent monitoring of blood glucose is
2
done
3 Electrolytes, acid base status and urinary ketone levels are checked.
If feasible surgery is delayed till blood glucose comes below 20
4
mmol/L and ketonuria disappears.
If delaying is not possible, operation with intensive management of
5
diabetic sate is to be done.
Other managements according to general principles of emergency
6
surgery should be followed.
187
P-C M-10 L-8 DM Management on Sick Days
During illnesses like fever, vomiting or diarrhoea, a diabetic person often develops hyper-
glycemia and ketosis, and sometimes hypoglycemia.
To prevent these, certain management principles are followed. These are:
Tests, Intake & Medicine

Blood or glucose and urine Intake of fluid & food The anti-diabetic medicine
for ketone
• Frequent tests for blood • Sufficient intake is nec- • The anti-diabetic agents
glucose & ketone in urine essary to maintain fluid should not be stopped
balance. altogether;
• If the blood glucose is • Dose of insulin/secre-
low, sweetened fluids, e.g. taguges may need to be
fruit juice is to be given to reduced.
avoid hypoglycaemia. • Longer acting secre-
• If blood glucose is taguges may need to be
elevated, low calorie soft replaced by shorter acting
drinks, soup or broth may ones or insulin.
be given. • In case of vomiting or
diarrhoea metformin/
• alfa-glucosidase
inhibitors is withdrawn
temporarily.
188
Some key points on Sick days management:
1. The principles of sick days are to be followed until the blood glucose is < 12 mmol/L
and ketone diminishes or disappears.
2. In situations with fever, the infective focus should be treated.
3. Treatment for vomiting/diarrhoea may also be required.
4. Hospitalization is considered if:
• Vomiting or diarrhoea persists for longer than 6 hours
• Sick for 2 days and not getting better.
• Moderate ketonuria persists despite treatment.
• Blood glucose remains above 14 mmol/L.
• Moderate ketonuria persists despite treatment.
• Very young individual.
• Abdominal pain.
• Hyperventilation.
• Co-existing serious diseases.
P-C M-10 L-9 Ramadan Fasting and Diabetes Mellitus
More than 50 million people with diabetes worldwide fast during Ramadan. During fasting
a Muslim must abstain from eating, drinking, use of oral medications, parenteral rehydrat-
ing or energy providing fluid or medication, and smoking from predawn (Sahur/sehri) to
sunset (Ifter). However, there are no restrictions on food or fluid from ifter to sehri.
Diabetic patients are at risk of harmful consequences due to the changes in pattern and
amount of food and fluid intake during Ramadan.
The harmful consequences associated with fasting are:

• Hypoglycemia (7.5 fold increase in severe hypoglycemia in T2DM)
• Hyperglycemia (5 fold increase in severe hyperglycemia in T2DM)
• Ketoacidosis,
• Dehydration and
• Thrombosis.
Severity of the risk in an individual i.e. categorization depends on factors namely diabetic
control, treatment regimen and co-existing disease.
189
P-C M-10 L-10 Categories of Risk in DM for Ramadan
There are 4 categories of risk in patients with diabetes who fast during Ramadan these
are as follows:
Risk categories Features
• Severe hypoglycemia within the last 3 months prior to
Ramadan
• Patient with history of recurrent hypoglycemia
• Patient with hypoglycemia unawareness
• Patient with sustained poor glycemic control
• Ketosis within the last 3 months prior to Ramadan
Very high risk group • Type 1DM
• Acute illness
• Hyperosmolar hyperglycemic coma within the last
3 months
• Patients who performs intense physical labor
• Pregnancy
• Patient on dialysis
• Patient with moderate hyperglycemia (average blood
glucose between 150 and 300 mg/dl, HbA1c7.5-9.0%)
• Patients with renal insufficiency
• Patients with advanced macrovascular complications
• People living alone who are treated with insulin or
Very high risk group
sulphonylureas
• Patients with comorbid conditions that presents addi
tional risk factors.
• Old age with ill-health
• Drugs that may affect mentation
Very high risk group • Well controlled patients treated with short acting secret
agogues such as repaglinide or nate glinide
Low risk group • Well-controlled patients treated with diet alone, met
formin ora thiazolidinedione who are other wise healthy.
N.B: As per ADA consensus
• Diabetic people belonging low and moderate risk group can perform Ramadan fasting and they
have to follow general measures of management.
• People in very high-risk group should observe the exemption for them regardingfasting.
• People in high-risk group should consult a diabetologist to have an individual assessment
before taking decision regarding fasting.
190
P-C M-10 L-11 Management of Diabetes During Ramadan
Management of diabetes during fasting should consist of pre-Ramadan medical assess-

ment and educational counseling. Persons eligible for fasting needs appropriate modifi-
cation in diet and drugs, and monitoring of blood glucose on regular basis,
General considerations
Frequent monitoring of glycemic status: Two important times are 2 hours after sehri and
1 hour prior to ifter. Testing at other times may also be done.
Nutrition: In terms of calorie and composition, diet should remain same healthy and
balanced as before Ramadan. Ingestion of large amount of foods rich in carbohydrate
and fats during ifter should be avoided. A complex carbohydrate that is slow in digestion
and absorption is good choice for sehri, while food with more simple carbohydrate may
be taken during ifter. Sehri (pre-dawn meal) should be taken as late as possible.
Exercise: Normal level of activity is recommended. Excessive physical activities may lead
to hypoglycemia. Tarawih prayer can be considered as part of daily exercise program.
Exercise between ifter and dinner may be undertaken.
Breaking the fasting: If blood sugar goes <3.3 mmol/L (60 mg/dl) at any time, or <3.9
mmol/L (70 mg/dl) during first few hours of sehri, or > 16.7 mmol/L (300 mg/dl), and on
sick days.
Medical assessment: Glycemic status, BP and lipid profile are to be stabilized before
Ramadan. Blood glucose must be checked frequently during the first few days of fasting
to readjust the doses of the medications.
191
P-C M-10 L-12 Specific Measures for T2DM & T1DM
Specific measures
Type 2 DM
• Patients on diet control only - risk during fasting is low.
• Patients on oral agents:
• Risk of fasting hypoglycemia is low if on insulin sensitizers or DPP-4 inhibitors or GLP-1
agonists; but risk increases when secretagogues (specially longer acting) are used.
• Biguanide - needs some dose adjustment.
• Glitazone, DPP-4 inhibitors and GLP-1 agonists, alpha glucosides inhibitors - need no
dose change.
• Secretagogues-glimepiride/glicazide-MR/glinides are preferred preparations; sulphonyl-
ureas need some dose adjustment; glinides need no dose change.
• Patients on insulin - dose readjustment is to be made according to the type of insulin.
• Patients on once-daily-drug-regimen (OAD or insulin) - the usual dose of antidiabetic
agent can be taken at sun-set; sometimes the dose may need to be reduced.
• Patients on twice-daily-drug-regimen (OAD or insulin) -the usual morning dose of
anti-diabetic agent is taken at sun-set; the evening dose is reduced to 50% and taken at
dawn.
• Patients on thrice-daily-drug-regimen (OAD or insulin):
• The total dose of metformin is divided into two-thirds to be taken at sun set, and
one-third at dawn.
• In case of rapid acting insulin or glinides the usual dose can be taken with meals.
• Short acting insulin is to be taken twice daily with larger share at sun-set.
• Patients on basal -bolus (4 times) insulin regimen - long acting insulin may be taken at
sunset in reduced dose with rapid acting ones 2-3 times with meals (may be in reduced
dose).
Type 1 DM
Some experienced physicians conclude that Ramadan fasting is safe for type l patients
with proper self-monitoring of blood glucose and close supervision. Two insulin regimens
have been studied successfully.
• Three-dose insulin regimen - two doses before meals (sunset and dawn) of short acting
insulin and one dose in the late evening of intermediate-acting insulin.
• Two-dose insulin regimen - evening insulin of combined short-acting and intermedi
ate-acting insulin equivalent to the previous morning dosage, and a predawn insulin
consisting only of short-acting insulin.
192
P-C M-10 L-13 Prevention of DM
• Diabetes mellitus, a chronic debilitating disease, is associated with a range of severe

complications.
• Prevention of diabetes is feasible and is evident in many studies done in various coun
tries.
• Prevention means preventing or delaying diabetes as well as the complications both in
terms of beginning and progression.
• The prevention is done by modifying the modifiable risk factors.
Types of prevention of diabetes mellitus
Tests, Intake & Medicine
Primary prevention Secondary prevention Tertiary prevention
Refers to avoiding the Means early detection of Aims to delay and/or

onset of the disease diabetes and prompt initia- prevent further progression
(diabetes) tion of treatment to prevent of the diabetic
complications of diabetes. complications.
193
P-C M-10 L-14 Primary Prevention
• Type 2 diabetes is the commonest form of diabetes.

• Although a heterogeneous disorder, progression from insulin insensitivity to pre-diabe
tes, then to diabetes is now well understood.
• The risk factors for type 2 diabetes are: a) aging, b) family history of type 2 diabetes,
overweight/obesity, d) physical inactivity e) pregnancy, f) intra-uterine and early child
hood malnutrition g) stress and h) smoking.
• Except age and family history all others are amenable to modification.
• Many of these risk factors are common for other non-communicable diseases (NCDs).
Primary prevention of type 2 DM

Prevention of type 2 DM is important because:
• It is the most prevalent type of diabetes.
• It is putting on tremendous burden:
• Rapidly and enormously rising number.
• Acute and chronic complications; 50% patients present with chronic complications.
• 15% patients have depression.
• 8.4% of global all-cause mortality.
• Economic impact- diabetics spend 10.8% of total health expenditure globally.
• Diabetes care is still suboptimal; less than one-third patients achieve target HbA1c.
It has recognizable pre-diabetic stage.
• It has identifiable risk factors.
• It is preventable by simple measures.

• It is part of NCDs having shared risk factors and benefit of prevention.
There is now substantial evidence that type2 DM can be prevented and its complica
tions can also be prevented or delayed. Identification of individuals at risk of developing
diabetes can be done effectively. Diabetes prevention programmes focus on lifestyle
modification, specifically modest weight loss and increased physical activity.
194
P-C M-10 L-15 Approach to Prevention of DM
Approaches of primary prevention

Primary prevention can be achieved through two basic approaches:
A. Population approach
B. High-risk group approach
1. Population approach
1. Creation of mass awareness
• Incorporation of basic information in school text book curriculums.
• Use of mass media, e.g. newspapers, radio, television etc.
• Use of social organizations, e.g. religious institutes, voluntary organizations etc.
2. Care of risk factors
• Creation of facilities for performing physical activities, like sports, gyms etc.
• Promotion of healthy eating habits, like campaign against 'fast food culture ‘etc.
2. High-risk group approach

This approach of primary prevention is in fact a clinical approach where physicians
perform the following activities:
1. Identification of people at risk
Risk factor of DM
Modifiable risk Non-modifiable risk
• BMI above normal (>25 kg/m2; for the • Age >40 years
Asians >23 kg/m2) • Positive family history of DM
• Habitual physical inactivity • Some ethnicities, eg Asians
• Waist-hip ratio above normal (>0.9 for
male; >0.8 for female)
• Previously identified as IFG/IGT
• History of GDM or delivery of baby >9
1bs
• PCOS, infertility, pregnancy loss, acan-
thosis nigricans
• Hypertension; dyslipidemia
2. Measurement of risk
• It is possible to identify and stratify people at increased risk based on age, BMI,
waist circumference, activity level, family history etc.
3. Intervention
• It is done by ensuring weight management, regular physical activity, medical
nutrition therapy and even by using drugs (like metformin) to modify the risk
factors.
195
Risks of type 2 DM in Asian countries
• Bangladesh and other Asian countries are at higher risk of type 2 diabetes and its
complications because:
• Risk of type 2 DM starts at lower BMI
• More prone to abdominal obesity, low muscle mass and insulin resistance
• Higher visceral or subcutaneous fat despite lower waist circumference or BMI
• Urbanization-rapid nutritional transition, reduced physical activity, mental stress
• Increase in smoking
• Intra-uterine or early childhood malnutrition
• Increased prevalence of GDM, risking mother and baby
• Chronic arsenic exposure
• Genetic susceptibility
• Earlier age of onset of DM
• More vulnerable to some complications, e.g. CAD, stroke, nephropathy, some
malignancies and all cause mortality.
Therefore, countries of this region should adopt their national policy to prevent diabetes
mellitus.
Primary prevention of type 1 DM

• For type 1 diabetes genetic and immunological markers are available but these are
costly.
• It is not feasible to use them for population-based identification, but specific high-risk
groups can be screened. The cost effectiveness, and social and moral issues of such
screening activities remain unclear.
• Some suggested strategies include encouraging breast-feeding, use of antioxidants
and beta cell rest by giving insulin to individuals with identified genetic and
immunological markers.
• As yet there is no evidence to suggest that type 1 diabetes can be prevented, but
none-the-less efforts continue, as it is a goal worth pursuing.
196
P-C M-10 L-16 Secondary Prevention of DM
Secondary Prevention
Early detection of diabetes and prevention of micro- and macro-angiopathies in a diabetic
person is termed secondary prevention. Studies documented that approximately 50% of
type2 diabetic patients already have complications at detection of their diabetes. Early
detection of diabetes to initiate its treatment thereby to halt or delay these complications
is the aim of secondary prevention.
Diabetes awareness in the community and amongst physicians to enhance the routine
screening of population at risk is important. Screening should be considered in all individ-
uals >40 years of age, and if normal should be repeated every 3 years. Screening should
be done at a younger age and/or more frequently in those with BMI >25 kg/m2 plus one
or more additional risk factors of diabetes (in the previous table). Testing for
pre-diabetes should be done yearly.
Target of secondary prevention of diabetes

Fasting/pre-meal <6.0 mmol/L
Blood (plasma) glucose Post-meal <8.0 mmol/L
HbAlc <7%
LDL cholesterol <100mg/dl

HDL cholesterol >40 mg/dl (male)
Blood lipids
>50 mg/dl (female)
Triglyceride <1 50 mg/dl
Target of blood pressure
Systolic <140mmofHg Diastolic

BP <80mmofHg
Target of body weight & obesity
BMI* <25 kg/m2 WC <90 cm (male)

BMI & Waist circumference (WC) <80 cm (female)
Teaching, training & empowerment to take
Target of diabetic education part in treatment
* Lower cutoffs may be appropriate for the Asians.2
197
Such an approach is cost effective, as costs of treating complications resulting from
undiagnosed and untreated diabetes are great. Several factors have been identified as
risk factors that are associated with deterioration of multiple organ function in a diabetic
person. In addition to glycemic. Control, strict control of blood pressure delays/prevents
development of retinopathy, nephropathy and cardiovascular diseases; control of lipid
abnormalities improves coronary, cerebrovascular and peripheral vascular complications.
Cessation of smoking, weight control and physical activity are beneficial.
P-C M-10 L-17 Tertiary Prevention of DM
Tertiary prevention
Interventions designed to minimize consequences of diabetes and help rehabilitation fall
under this category. Here attempts are directed to contain damage by aggressive therapy
to arrest or delay progression of complications. Each complication may be addressed
with special objectives and strategies reducing morbidity and mortality.
Screening for complications
Type 1 DM
• At or after 5 years of diagnosis (or earlier); then every year
(in absence of complications)
Type 2 DM
• At diagnosis; then every year (in absence of complications)
Effective strategies of tertiary prevention
Prevention of lower limb amputation

• Imp roved foot ca re
• Reduction of risk factors
• Control of hyperglycemia, etc.
Prevention of cardiovascular disease

• Control of hypertension
• Control of dyslipidemia
• Cessation of smoking
198
Prevention of renal disease
• (When necessary) low protein diet
Prevention of blindness
• Laser photocoagulation
Diabetic complications account for 60% of diabetes related health care costs
(direct costs) and almost 80-90% of indirect costs. Preventing complications
is therefore not only beneficial to individuals but also to the society as a
whole. Economic analysis from the different studies has shown that preven-
tion programs are cost effective. Other studies also have shown that simple
measures, like education and awareness also help.
Comprehensive care of diabetes with patient education and awareness

about complications can bring about a remarkable reduction in blindness,
end-stage renal diseases (ESRD), lower extremity amputation and cardiovas-
cular events.
199
P-C M-10 L-18 Epidemological Aspect of Tuberculosis and Diabetes
In 1993, World Health Organization (WHO) declared TB as a global emergency because

globally Tuberculosis is emerging rapidily. Several epidemiological studies demonstrated
that subjects with diabetes are three to five times at higher risk of getting active TB disease
compared to those without diabetes, and often they do not have classical feature and can
develop Multi-Drug Resistant Tuberculosis (MDR TB) and Extensively Drug Resistant
Tuberculosis (XDR TB).
According to WHO Tuberculosis Profile, 2020

Globally:
• In 2019, about 9.80 million fell ill with active TB disease. Among them 58% were men,
35% were women and 7% were children.
In Bangladesh:
• Incidence rate of all forms of TB was 217 per 100000 populations per year.
• Prevalence of all forms of TB was 260 per 100000 populations per year.
• TB death rate of all forms of TB was 27 per 100000 populations per year.
Need to Know:
• Persons who have been recently infected with TB bacilli M. tuberculosis is carried in
air borne particles, called droplet neuclei, infectious droplet neuclei are generated by
coughing, sneezing, shouting and singing of persons who have pulmonary or laryngeal
TB disease.
• Kniwn risk factors of Tuberculosis are as follow, persons with medical conditions
which causes immunosuppression such as diabetes mellitus, HIV, CKD, people on
chemotherapy etc. and people suffering from malnutrition and living in over-crowded
areas.
• People with diabetes mellitus have the chance of TB infection is about 30% over
lifetime.
• People with no risk factor have the chance of TB infection is about 10% over lifetime.
200
Tuberculosis and Diabetes:
P-C M-10 L-19 Presentation, Clasification & Diagnosis
Common syptoms of Pulmunary TB are Cough (dry or productive), fever with night sweting,
anorexia, weight loss, generalized weekness, chest pain, haemoptysis, shortness of breath.
Symptoms of Extra-pulmonary TB depends on the site involved. The respective sites

and the common symptoms as follow,
TB lympadenitis: Lymph node swelling Bone TB: Pain and swelling in the
1 5 particular joint
Tuberculous serous effusion Genito-urinary TB: Dysuria, Fever,

2 (pleural, pericardial, peritoneal): Chest 6 Lower Abdominal pain
pain, shortness of breath,
Gastro-intestinal TB: abdominal pain, Hepatic/splenic TB: Fever, Abdominal
3 swelling, constipation, diarhoeea 7 pain, Altered liver function
Spinal TB (Pott`s disease): Back pain, CNS tuberculosis: Headache, fever,

4 paraplegia 8 altered level of consiouness, convulsion
Case definition can be done by following ways. Shown in table

TB Case Definition
1 On basis of site and bacteriological status in adults
A Pulmonary TB Patient with TB which infects the lungs
A1 Bacteriologically (After abnormality detection by chest x-ray or if x-ray is not
confirmed smear available) Patient found positive on gene xpert Or,
positive Pulmonary with at least one sputum specimen positive for AFB, including
TB (PTB+) any scanty smear result Or,
Patient with symptoms suggestive of TB with two sputum
specimen negative for AFB and found positive on Xpert
(MTB/RIF)
A2 Clinically Diagnosed Patient with the findings of chest X-ray abnormalities consistant
with active TB with gene xpert negative or two sputum
specimen negative for AFB.
(Diagnosis is made by a qualified physician)
B Extra-pulmonary TB Patient with TB of organ other than the lungs as confirmed by

(EPTB) a qualified physician
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2 On the basis of anti-TB drug resistance
A Mono-resistant Resistant to one anti-TB drug.
B MDR-TB: When TB bacilli are resistant to Rifampicin and Isoniazid

with/without other 1st line anti-TB drug
C XDR-TB: When M. tuberculosis strains that fulfil the definition of

MDR/RR-TB and which are also resistant to one of the
fluroquinolones and one of the three injectable second line drugs.
3 On basis of previous treatment history

A New Patient who has never received anti-TB drug or, patient who
received anti-TB drug for <1 month
B Relapse Previously treated TB patient who has been declared ‘cured’ or
‘treatment completed’ and is diagnosed with bacteriologically
positive (smear or culture) tuberculosis
C Treatment after Patient previously been treated for TB and treatment failed at the
failure end of their most recent course of treatment
D Loss to follow up previously treated TB patient, declared loss to follow up at the
end of most recent course of treatment
E Transfer in Patient who is already registered for treatment in DOTS center
and is subsequently transferred to another registration unit.
F Other (s) All cases that do not fit the above definitions
Tools for Diagnosis of Tb

1 Radiological (X-ray) Common findings include- dynamic changes in opacity,
examination of the lungs patchy opacity specially in apical area and cavitary lesion.
2 Sputum smears Cost-effective tool. Sputum microscopy is likely to be
examination by microscopy positive when there are at least 5000 bacilli/ml of
sputum. At concentration <1000 bacilli/ml of sputum,
the chance of finding AFB in a smear is less than 10%.
3 Molecular test Genexpert MTB/RIF. Genexpert detects the DNA in TB
bacteria and also give information on rifampicin
resistant status. Its an effective diagnostic tool.
4 Other:
• Culture of TB bacilli DST (Drug Susceptibility Test)

• Histopathol
• Tuberculin skin test (Mantoux test)
202
Tuberculosis (Tb) – Diabetes Mellitus (Dm) Comorbidity
Diabetes makes a substantial contribution to the incidence of TB and the association is
particularly strong for the infectious form of TB. On the other hand, TB can cause any
form of glucose intolerance and lead to increased incidence of diabetes mellitus.
Screening criterias and Tests
A TB in patients with DM DM in patients with TB
1 DM patient having typical features of TB 1 Diabetes screening is recommended for
• Cough & sputum for ≥ 2 weeks all adults older than 18 years with TB
• Low grade fever

• Weight loss
2 DM patient with some unusual features: 2 TB patients with following risk factors
• Unintentional weight loss in a patient for DM:
with good glycaemic control • Old age (> 40 years)
• Night sweats not due to nocturnal • Obesity
hypoglycemia • Inactive lifestyle
• Sudden unexplained deterioration of • Family history of DM
glycaemic status
• Patient who develop symptoms of
hyperglycemia during TB treatment
2 **DM patients with TB may not present all the typical symptoms of Tuberculosis.
B Tests in patients with DM Tests in patients with TB
After clinical assessment After clinical assessment
a) Chest X-ray a) Fasting plasma glucose/ OGTT
b) Genexpert test (Oral glucose tolerance test)
c) Sputum for AFB b) HbA1c%
203
P-C M-10 L-20 Tuberculosis And Diabetes: Treatment
Treatment and cure of infectious cases of TB will cut the chain of transmission of TB
infection in the community. Therefore, successful completion of TB treatment is the most
effective way of prevention of TB.
Drugs used in TB treatment:

Drugs used in TB treatment are divided in two
First line drug Second line drugs
• Isoniazid (INH) • Levofloxacin
• Rifampicin (RIF) • Moxifloxacin
• Ethambutol (EMB) • Bedaquiline
• Pyrazinamide (PZA) • Delamanid
• Linezolid
• Pretomanid
Dosage of Fixed dose combination (FDC) tablets:

4-FDC: isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg
3-FDC: isoniazid 75 mg + rifampicin 150 mg + ethambutol 275 mg
2-FDC: isoniazid 75 mg + rifampicin 150 mg
Treatment regimen for Adult TB

Patients recommended for category I Patients recommended for Re-treatment
• New bacteriologically confirmed smear +ve • Sputum smear-positive PTB with history of
PTB patients treatment of ≥1 month
• Clinically Diagnosed • Relapse
• New extra-pulmonary TB • Treatment failure
• After loss to follow up
• Others
Dose of Drugs
1. Category I:
Name of Drug Body weight Duration
30 -37 Kg 38-54 Kg 55-69 Kg ≥ 70 kg (in months)
4FDC No. of Tab 2 3 4 5 2
2FDC No. of Tab 2 3 4 5 4
2. Re-treatment Cat: Genexpert is needed to be done before starting anti-TB medication.
204
2.1. For Rifampicin sensitive Cases:
Type Name of Drug No. of Tablet Months
• Bacteriologi cally 4FDC As per body weight described in Cat I 06
confirmed smear
Levofloxacin < 33kg 7.5 – 10 mg/kg; 06 (single dose
+ve PTB patients
daily)
and 33 – 50 kg 750mg;
• EPTB
51 – 70kg 750mg;
> 70kg 1000mg;
• Clinicaly Diagnosed 4FDC As per body weight described in Cat I 06
• TB meningities, 4FDC As per body weight described in Cat I 12

• Bone TB, Levofloxacin < 33kg 7.5 – 10 mg/kg; 12 (single dose
• Neurological TB daily)
33 – 50 kg 750mg;
51 – 70kg 750mg;
> 70kg 1000mg;
2.2. Rifampicin Resistance patients need to be refrred for MDR treatment.
Treatment of TB in Diabetics
1. Choice of anti-diabetic drugs in TB patients:

• Rifampicin increases the hepatic metabolism of metformin and all sulphonylurea
derivatives. This effect on sulphonylurea has great inter-individual variation which
makes dose adjustments difficult and increases a patient`s risk of hyperglycaemia or
hypoglycaemia.
• Less is known about newer anti-diabetic drug classes
• Rifampicin probably has no effect on the exposure of glucagon
• If oral anti-diabetic drug (OAD) is to be used in a TB patient, then avoid metformin.
Among sulphonylureas e.g. glimepiride has less interaction with anti-TB drugs.
2. Indication of insulin for control of diabetes in TB-DM patients:

• Severe TB infection like- dissiminated TB, military TB, TB meningitis
• Loss of tissue and function of pancreas due to- pancreatic endocrine deficiency and
tuberculous pancreatitis
• Lean and thin patients with- requirement for high calorie, high protein diet and need
for anabolic effect
• Uncontrolled DM (HbA1C >7%) in patient getting OAD
• Any compelling indication of insulin or contraindication of OAD
205
3. Use of steroid in TB-DM patients:
• If TB-DM patient requires systemic steroid for treatment of TB then it must be given
in the required dose
• The dose of insulin must be adjusted accordingly
• If the patient was on OADs then must be switched to insulin
• In critically ill patient with uncontrolled diabetes requiring systemic steroid, insulin
infusion may be used temporarily
4. Special consideration in treating TB in DM patients
• Patient must be treated according to standard category
• Almost all anti-TB drugs are safe in a diabetic patient without other co-morbidity
• Baseline renal and liver function should be assessed before starting anti-TB therapy,
• Careful and frequent monitoring is required as there is increased chance of
hepatotoxicity
• Many of the diabetic patients have associated nephropathy. In these patient’s dose
modification of nephrotoxic anti-TB drugs e.g. ethambutol,
• Rifampicin can cause hyperglycemia directly or indirectly via interactions with oral
hypoglycemic drugs
• Rifampicin reduces the bioavailability of most of the sulphonyluraes, metformin and
thiazolidinediones
• Isoniazid can antagonize the release and action of insulin
• Isoniazid and rifampicin can interfare with the intestinal absorption of carbohydrate
• So, for every DM patient glycemic status should be checked within 02 weeks of starting
anti-TB and DM medications should be adjusted accordingly. And if the initial renal
and liver functions were not assessed then these assessments need to be completed
along with the glycaemic status of the patient within 02 weeks of starting the anti-TB
medication.
206
There are 19 sections in this module 10. I understand the following points.
• The basic principles of management of diabetes mellitus during surgery.
• The special care during days of sickness.
• The special aspects of Ramadan fasting.
• How to prevention of diabetes mellitus.
• How to diagnose and treat diabetes with tuberculosis togather
Further reading
1. Text Book of Diabetes, 4th edition, edited by Richard l G Holt, Clive S Cockram,
Allan Flyvbjerg & Barry J Goldstein, Wiley-Blackwell, 2010
2. Davidson’s Diabetes Mellitus- Diagnosis & Treatment, 5th edition,
edited by A P Harmel & R Mathur, Saunders, 2004.
3. Clinical Diabetes- Translating Research into Practice, 1st edition, VA Fonseca,
Saunders, 2006.
5. Recommendations of Management of Diabetes during Ramadan, Update 2010,
Diabetes Care, volume 33, number 8, 2010.
6. Prevention of Diabetes Mellitus, WHO (World Health Organization) Technical
Report Series 844, 1994.
7. Development Programme for the PREVENTION & Care of Diabetes in Finland,
Finnish Diabetes Association, 2001.
8. Güneylioglu D, Yilmaz A, Bilgin S, Bayram U, Akkaya E. Factors affecting delays in
diagnosis and treatment of pulmonary tuberculosis in a tertiary care hospital in
Istanbul, Turkey. Medical Science Monitor. 2004 Feb 1;10(2):CR62-7.
9. World Health Organization (WHO). Global tuberculosis report, 2020.
10. NTP. National Guidelines and Operational Manual for Tuberculosis Control. 5th
edition, reprint 2015.
11. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a
systematic review of 13 observational studies. PLoS Med. 2008 Jul 15; 5(7): e152
207
Further reading
1. Text book of Diabetes, 4th edition, edited by Richard I G Holt, Clive S Cockram, Allan
2. Diabetes Atlas, 8th edition, IDF (International Diabetes Federation), 2017.
3. Davidson's Diabetes Mellitus -Diagnosis & Treatment, 5th edition, edited by A P Hamel
Saunders, 2006.
5. From the Triumvirate to the Ominous Octet: A new Paradigm for the Treatment of
Type 2 Diabetes Mellitus, Ralph A DeFronzo, Diabetes, 2009.
6. Davidson's Diabetes Mellitus -Diagnosis &Treatment, 5th edition, edited by A P Hamel
7. Clinical Practice Recommendations, ADA (American Diabetic Association), 2014.
8. Global Guideline for Type 2 Diabetes, Clinical Guidelines Taskforce, IDF (International
Clinical Endocrinologist) Task Force, 2013.
10. Patient's Guide Book, Diabetic Association of Bangladesh.
Harmel& R Mathur, Saunders, 2004.
Clinical Endocrinologists) Task Force, 2017.
Harme l& R Mathur, Saunders, 2004.
Report from the Panel Members Appointed to the Eight Joint National Committee
(JNC 8) 2013.
19. Guideline on the Treatment of Blood cholesterol to Reduce Atherosclerotic
208
20. Cardiovascular Risk in Adults, a Report of the ACC (American college of
Cardiology)/AHM (American Heart Association) Task Force on Practice
Guidelines, 2013.
21. Davidson’s Diabetes Mellitus-Diagnosis & Treatment, 5th edition, edited by A P
Harmel & R Mathur, Saunders, 2004.
22. Global Guideline of Type2 Diabetes, Clinical Guidelines Task Force, IDF (International
Evaluation & Federation), 2012
Evaluation & Treatment of High Blood Pressure (JNC 7), 2004.
25. Third Report of the NCEP (National Cholesterol Education Program) Expert Panel on
Detection, Evaluation & Treatment of High Blood Cholesterol in Adults
(Adult Treatment panel III), 2001 (Revised in 2004).
27. Global IDF (International Diabetes Federation) /ISPAD (International Society for Pedi
atric & Adolescent Diabetes) Guidline for Diabetes in Childhood & Adolescence, 2011.
28. Global Guideline for Managing Older people with Type 2 Diabetes, IDF (International
29. Diagnostic criteria & Classification of Hyperglycemia First detected in Pregnancy,
WHO (World Health Organization) 2013.
30. International Association of Diabetes & Pregnancy Study Groups Recommendations
on the Diagnosis & Classification of Hyperglycemia in Pregnancy, Diabetes Care,
volume 33, number 3, 2010.
31. Diabetes and Pregnancy, an Endocrine Society Clinical Practice Guideline, 2013.
Harmel & R Mathur, Saunders, 2004.
33. Recommendations of Management of Diabetes during Ramadan, Update 2010,
Diabetes Care, volume 33, number 8, 2010.
34. Prevention of Diabetes Mellitus, WHO (World Health Organization) Technical Report
Series 844, 1994.
35. Development Programme for the PREVENTION & Care of Diabetes in Finland, Finnish
Diabetes Association, 2001.
36. Standards of Medical Care in Diabetes, ADA (American Diabetes Association), 2021.
209
37. Diagnosis and Classification of Diabetes Mellitus and Intermediate Hyperglycemia,
Report of a WHO (World Health Organization)/IDF (International Diabetes Federation),
2006.
38. Güneylioglu D, Yilmaz A, Bilgin S, Bayram U, Akkaya E. Factors affecting delays in
diagnosis and treatment of pulmonary tuberculosis in a tertiary care hospital in
Istanbul, Turkey. Medical Science Monitor. 2004 Feb 1;10(2):CR62-7.
39. World Health Organization (WHO). Global tuberculosis report, 2020.
40. NTP. National Guidelines and Operational Manual for Tuberculosis Control. 5th
edition, reprint 2015.
41. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: a
systematic review of 13 observational studies. PLoS Med. 2008 Jul 15; 5(7): e152
210
Address
DLP Office
Room# 331, 2nd Floor
BIRDEM General Hospital
122 Kazi Nazrul Islam Avenue
Shahbag, Dhaka-1000

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Certificate Course on Diabetology (CCD)

Distance Learning Program (DLP)

For Certificate Course on Diabetology (CCD) Batch-35

The Bangladesh Diabetic Somiti (BADAS)/Diabetic Association of Bangladesh (DAB) is

National Professor Professor Hajera Mahtab Professor Tofail Ahmed

Lesson-2 Definition of Diabetes Mellitus 3

Lesson-3 Classification of Diabetes Mellitus 4

Lesson-4 Type 1 Diabetes Mellitus 5

Lesson-5 Type 2 Diabetes Mellitus 5

Lesson-6 Other Specific Types of Diabetes Mellitus 6

Lesson-7 Gestational Diabetes Mellitus (GDM) 6

Lesson-8 Diabetes Complications 7

Lesson-9 Treatment of Diabetes 7

Lesson-10 Epidemiology of Diabetes Mellitus 8

Lesson-11 Global trend 9

Lesson-12 South-East Asia trend 10

Lesson-13 Bangladesh and Indian trend 11

Lesson-14 Diabetes in the young 12

Lesson-15 Morbidity and Mortality 13

Lesson-3 Clinical presentation: Asymptomatic 17

Lesson-4 Clinical Presentation: Typical 17

Lesson-5 Clinical presentation: Atypical 18

Lesson-6 Presentation: Complications of DM 19

Lesson-7 Blood (plasma) glucose tests 20

Lesson-8 OGTT: Result interpretation 20

Lesson-9 FPG: Result interpretation 22

Lesson-10 RPG: Result interpretation 23

Lesson-11 HbA1c: Result interpretation 24

Lesson-12 OGTT Procedure 25

Lesson-16 T1DM vs T2DM 29

Lesson-2 Introduction to Aetiopathology 34

Lesson-5 Insulin secretion 37

Lesson-6 Tissue & insulin action 38

Lesson-7 Insulin secretion in healthy subjects 39

Lesson-8 Glucose homeostasis during fasting state in healthy subject 40

Lesson-9 Glucose homeostasis after food intake in healthy subjects 41

Lesson-10 Glucose homeostasis during fasting state in healthy subject 42

Lesson-11 Risk factors of diabetes 43

Lesson-12 Pathogenesis of Type 1 DM 44

Lesson-13 Pathogenesis of Type 2 DM 45

Lesson-14 Insulin release in T2DM 46

Lesson-15 Beta cell failure 47

Lesson-16 Insulin resistance & Metabolic syndrome 48

Lesson-17 Incretin, Glucagon, SGLT-2, Brain factors and T2DM 51

Lesson-2 General Principles in Management of DM 55

Lesson-3 Aims and steps of Treatment of DM 57

Lesson-4 Step 1. Diagnosis and 2. Factor Analysis 58

Lesson-5 Step 3. Targets of Treatment 59

Lesson-6 Step 4: Selection & Initiation of a Treatment Regimen 60

Lesson-7 IStep 5: Monitoring & Changing Treatment Regimen 61

Lesson-8 Step 6: Complications Screening, Referral & Step 7: Treatment Evaluation 63

Lesson-9 Lifestyle Modification in DM 63

Lesson-11 MNT: Calorie Requirement 65

Lesson-12 MNT: Component of Nutrients 66

Lesson-13 MNT: Carbohydrates, Fat & Protein 66

Lesson-14 MNT: Vitamins, Sweeteners & Alcohol 67

Lesson-15 MNT: Weight Management 68

Lesson-16 Meal Timing, Composition and Planning 69

Lesson-17 Anthropometric Measurement 70

Lesson-18 Exercise and DM 71

Lesson-3 Oral anti-diabetic drugs (OADs) 78

Lesson-4 Sulfonylureas and Glinides 81

Lesson-5 Metformin & Thiazolidinediones 84

Lesson-6 Alpha-glucosidase inhibitors & DPP-4 inhibitors 85