DM Guidelines

FEDERAL DEMOCRATIC REPUBLIC OF ETHIOPIA
MINISTRY OF HEALTH
National Training on
Diabetes Mellitus
for Health Care Workers
Participant’s Manual
Addis Ababa
October 2016
1
National Diabetes Mellitus Training 2016 Page 2
TABLE OF CONTENTS
ACKNOWLEDGMENT ............................................................................................................................ 4
ACRONYMS ............................................................................................................................................ 6
BACKGROUND AND INTRODUCTION ABOUT THE COURSE ............................................................. 8
UNIT I: DEFINITIONS & EPIDEMIOLOGY OF DIABETES MELLITUS ............................................... 12
UNIT 2: CLASSIFICATION AND PATHOGENESIS OF DIABETES MELLITUS ................................... 18
UNIT 3: CLINICAL MANIFESTATIONS OF DIABETES MELLITUS & MANAGEMENT OF ACUTE
COMPLICATIONS ................................................................................................................................. 27
UNIT 4: CHRONIC COMPLICATIONS OF DIABETES MELLITUS....................................................... 39
UNIT 5: MANAGEMENT OF TYPE 1 DIABETES MELLITUS .............................................................. 51
UNIT 6: MANAGEMENT OF TYPE II DIABETES: LIFE STYLE INTERVENTIONS AND ORAL
AGENTS ................................................................................................................................................ 64
UNIT 7: INSULIN INITIATION AND TITRATION IN TYPE 2 DIABETES .......................................... 81
UNIT 8: DIABETES IN CHILDREN AND ADOLESCENTS ................................................................... 88
ANNEXES ............................................................................................................................................ 117
ANNEX I: INSULIN INITIATION AND DOSE ADJUSTMENT IN TYPE 1 DM ............................... 117
ANNEX II: ALGORITHM FOR OUTPATIENT MANAGEMENT OF TYPE 2 DIABETES ................ 118
ANNEX III: ALGORITHM FOR MANAGEMENT OF DIABETIC KETOACIDOSIS (DKA) AND
HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS) .................................................................... 119
ANNEX IV: ALGORITHM FOR MANAGEMENT OF HYPOGLYCEMIA IN DIABETIC PATIENTS ON
TREATMENT WITH GLUCOSE LOWERING AGENT OR INSULIN............................................... 121
ANNEX V: DKA MANAGEMENT PROTOCOL IN CHILDREN ....................................................... 122
ANNEX VI. SCREENING FOR THE HIGH RISK DIABETIC FOOT: A 60-SECOND TOOL ............ 125
ANNEX VII: BLOOD PRESSURE CHART FOR CHILDREN ............................................................ 127

ACKNOWLEDGMENT
The development of this National Diabetes Mellitus Modular Training Manual for Health Care
Workers is based on the National Guidelines on Clinical and Programmatic Management of
Major Non Communicable Diseases
This material has been developed by experts in the field from Addis Ababa University and
Ethiopian Diabetes Association and Federal Ministry of Health after a series of consultations.
The Ministry of Health would like to recognize the contributions of the following experts
NAME CONTRIBUTIONS AREA OF SPECIALTY AND

ORGANIZATION
Prof. Yewoinhareg Feleke Clinical Manifestations of Consultant Internist and
Diabetes mellitus and its Acute Endocrinologist, AAU
complications
Dr Ahmed Reja Management of Type 1 Diabetes Consultant Internist and
Mellitus Diabetologist, AAU
Dr Tedla Kebede Classification and Consultant Internist and
Pathogenesis of Diabetes Diabetologist , AAU
Mellitus
Dr Helen Yifter Insulin initiation and titration Consultant Internist and
in Type 2 diabetes Endocrinologist,
AAU
Dr Abdurezak Ahmed Life Style Interventions and Consultant Internist and
Oral agents in the management Endocrinologist,
of Type II diabetes AAU
Dr Bereket Fantahun Management of Childhood Pediatrician, Pediatrics
Diabetes Endocrinologist
and Diabetologist,
AAU
Dr Moges Kibebew Definition and Epidemiology of Consultant Internist and
DM Diabetologist
Dr Bisrat Alem Chronic Complications of Internist and Endocrinology
Diabetes Mellitus Fellow, AAU
Dr Molla Gedefaw Reviewer Team MD, Public Health, NCD Case
Team Coordinator/FMOH
Dr Yoseph Mamo Reviewer Team Internal Medicine, Jimma
University
Dr Wubaye Walelgne Reviewer Team Internal Medicine, NCD Case
Team, FMOH/ PIH
Dr Mussie G/Michael Reviewer Team MD,MPH, NCD Case Team/
FMOH
Dr Asmamaw Bezabeh Reviewer Team MD,MPH, NCD Case team

WHO/FMOH

The FMOH would like to pass its gratitude for Novartis Pharma Services AG and Sandoz GmbH
for generously supporting the development and printing of the training UNITs and related tools.
FMOH expects that this training will help improve the early identification and management of
Diabetes in the country there by decreasing the suffering and death associated with this
common chronic non communicable disease.
Amha Fantaye, MD, MHA

Director,
Diseases Prevention and Control Directorate

ACRONYMS
ADA American Diabetes Association

ACE-I angiotensin converting enzyme inhibitor
ACR albumin:creatinine ratio
AER albumin excretion rate
ARB angiotensin-II receptor blocker
BMI body mass index
BP blood pressure
CCB Calcium Channel Blocker
CSII continuous subcutaneous insulin infusion
CT computed tomography
CV cardiovascular
CVD cardiovascular disease
DM Diabetes Mellitus
DCCT Diabetes Control and Complications Trial
DKA diabetic ketoacidosis
DSME diabetes self-management education
eGFR estimated glomerular filtration rate
HbA1c glycated haemoglobin
HDL-C high-density lipoprotein cholesterol
HTN Hypertension
IDF International Diabetes Federation
IM intramuscular
IV intravenous
LDL-C low-density lipoprotein cholesterol
MDI multiple daily injections
NCD Non communicable Diseases
NPH neutral protamine Hagedorn
OGTT oral glucose tolerance test
PCOS polycystic ovary syndrome
SC subcutaneous

SMBG self-monitoring of blood glucose
TDD total daily dose
TDEI total daily energy intake
TSH thyroid stimulating hormone
WHO World Health Organization

BACKGROUND AND INTRODUCTION ABOUT THE COURSE
i. INTRODUCTION
Non communicable diseases are chronic conditions that do not result from an acute infectious
process but infectious diseases can be a contributing cause; NCDs cause death, dysfunction, or
impairment in the quality of life.
Non-communicable diseases are the leading causes of death globally, killing more people each
year than all other causes combined. Contrary to a widely held opinion, available data
demonstrate that nearly 80% of deaths due to non-communicable diseases occur in low- and
middle-income countries.
The World Health Organization estimate in 2008 showed 34% of death among Ethiopian
population was from non-communicable diseases; in which case cardiovascular disease
comprised of 15%, Cancer and Chronic Obstructive Pulmonary Diseases 4% each and Diabetes
Mellitus 2%.
Diabetes Mellitus is one of the four major NCDs causing a high morbidity and mortality. Data
from the National STEPS Survey conducted in 2015 in Ethiopia showed the prevalence of DM or
raised blood sugar in the adult population is 6%.
ii. SCOPE OF THIS TRAINING MANUAL
This participant manual is intended to serve as the main tool to deliver the National Diabetes
training component of the National Major NCD training curriculum.
Target groups for this course include:
o Physicians(Internists, Pediatricians,GPs)
o Health officers and BSc Nurses
o Nurses and
o NCD Focal persons at National and Regional level
All professionals working in public (including other governmental health institutions), private
(including workplaces) and nongovernmental organizations working in the care of Diabetes
patients are expected to be trained with this training package.
iii. COMPONENTS OF DM & HYPERTENSION TRAINING PACKAGE
The National DM and HTN Training manual has two sections:

1. DM Training Manual with 8 Units
2. Hypertension Training Manual with 10 Units

iv. DM TRAINING METHODS AND MATERIALS
This participant manual uses modular type of training with a variety of teaching methods and
instruction, including reading, written exercises & case studies, discussions, demonstrations and
site visits. Written exercises and clinical practices are considered critical element of instruction.
The training is designed for small groups of 20-25 participants who are led and assisted by
“facilitators” as they work through the UNIT
Each participant will receive the following materials:
 The national Diabetes Training Manual

 The national Guidelines on Clinical and Programmatic Management of Major NCDs
 Provider support tools and Client education materials on Diabetes
At the end of each training day, participants are expected to spend 30 minutes to respond to
exercises designed to review the topics covered over the day; and responding to the exercises
and follow-up discussion should be part of Recap session on the beginning of the next training
day. Answers with explanation for the questions are provided on the facilitator guide.
A pre- and post-assessment of knowledge of diabetes diagnosis and management, and general
course evaluation.
v. DURATION OF THE COURSE
The Diabetes Training course is designed to be delivered with Hypertension Training Course
and in the future with other NCD Topicss. The training will be delivered in three days excluding
the M&E and logistics section.
vi. TRAINING OBJECTIVES
LEARNING OBJECTIVES: developing the essential knowledge, attitude and skill to
prevent development of diabetes and its complications, treat acute complications and
care for chronic disabilities resulting from diabetes.
The trainees should demonstrate the following core competencies after successful
completion of the training.
1. Application of the concepts and principles of Diabetic management
2. Taking and documenting General and specific history from the patient

3. Assessing and managing according to the national diabetic management
guideline
4. Acquiring knowledge skills, and confidence in the use of insulin and oral
hypoglycemic agents
5. Communicating with patients and their families and providing ethical, patient-
centered care
6. Recognizing the importance of effective management as a way of preventing
acute life threatening an chronic disabling complications
7. Recognizing the importance of working as team for effective diabetes
management
8. Assessing and managing the psychosocial, spiritual and cultural dimensions of
through counseling and other non-pharmacological approaches
National Training on Diabetes Mellitus: Course Agenda
Day 1
Time Frame Activity Facilitator
8:30-9:00 am Registration of trainees
9:00- 9:10 am Welcoming and key note address
9:10-9:30 am Pre-training knowledge, attitude and
practice evaluation
9:30-9:45 am Setting the agenda
9:45-10:00 am Tea/Coffee Break
10:00 am-11:00 am UNIT 1: DEFINITIONS and EPIDEMIOLOGY
OF DIABETES MELLITUS
11:00 am-12:30 pm UNIT 2: CLASSIFICATION AND
PATHOGENESIS OF DIABETES MELLITUS
12:30-1:30 pm Lunch
1:30-3:30 pm UNIT 3: CLINICAL MANIFESTATIONS OF
DIABETES MELLITUS AND ITS ACUTE
COMPLICATIONS
3:30-4:00 pm Tea/coffee break
4:30-5:30 pm UNIT 3: CLINICAL MANIFESTATIONS OF
DIABETES MELLITUS AND ITS ACUTE
COMPLICATIONS
Day 2
8:30-9:00 am RECAP SESSION

9:00-10:20 UNIT 4: CHRONIC COMPLICATIONS OF
DIABETES MELLITUS

10:20-10:40 Tea/Coffee Break
10:40-11:30 UNIT 4: CHRONIC COMPLICATIONS OF
DIABETES MELLITUS
11:30-12:30PM UNIT 5: MANAGEMENT OF TYPE 1 DIABETES
MELLITUS
12:30-1:30 Lunch
1:30-4:00 UNIT 6: MANAGEMENT OF TYPE II
DIABETES: LIFE STYLE INTERVENTIONS
AND ORAL AGENTS
4:00-4:20 Tea/Coffee Break
4:20-5:30 UNIT 6: MANAGEMENT OF TYPE II
DIABETES: LIFE STYLE INTERVENTIONS
AND ORAL AGENTS
Day 3

8:30-9:00 am RECAP SESSION
9:00-10:00 am UNIT 7: INSULIN INITIATION AND
TITRATION IN TYPE 2 DIABETES
10:00-10:20 am Tea/Coffee Break
10:20 am-12:30 pm UNIT 8: MANAGEMENT OF CHILDHOOD
DIABETES
12:30-1:30 pm LUNCH
1:30-3:30 pm Teach back session on DM and HTN
3:30-4:00 pm Tea/coffee break
4:00-5:00 pm Post test
5:00-5:15 Closing of DM Training

UNIT I: DEFINITIONS & EPIDEMIOLOGY OF DIABETES MELLITUS
Total Time Allotted for UNIT 1: 1 hour
UNIT Objectives
By the end of this session the participant will be able to:
• Define key terms in diabetes and describe the diagnostic criteria for DM
• Describe the initial approach in the work up of a diabetic patient
• Describe the global and regional epidemiology of diabetes
• Describe the national epidemiology of diabetes
• Explore the various barriers to care
• Explain strategies for prevention of DM
DEFINITION OF DIABETES MELLITUS
Diabetes is defined by the World Health Organization (WHO) as a metabolic disorder

characterized by chronic hyperglycemia associated with disturbances of carbohydrate, fat and
protein metabolism resulting from defects in insulin secretion, insulin action, or both.
It is accompanied by a marked propensity to develop relatively specific forms of renal, ocular,

neurologic, and premature cardiovascular diseases.
DIAGNOSIS of DM
Diabetes is diagnosed by laboratory measurement of glucose or glycosylated hemoglobin level
in a blood sample. Fasting blood glucose is likely to be the most feasible measurement in
primary health care facilities.
As the diagnosis of diabetes leads to enrolment into chronic care with huge implications for the
patient, the family and the health care system diagnosis should be ascertained by repeat testing.
DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS (ADA 2016)

Category Fasting Plasma Glucose 2hr 75g OGTT HbA1C
Normal <100 mg/dL <140 mg/dL <5.6%
(<5.6 mmol/L) (<7.8 mmol/L)
Prediabetes 100-125 mg/dL 140-199 mg/dL 5.7–6.4%
(5.6–6.9 mmol/L ) (7.8–11.0 mmol/L)
>126 mg/dL ** > 200 mg/dL ** > 6.5% **

(> 7.0 mmol/L) (> 11.1 mmol/L)
Diabetes In a patient with classic symptoms of hyperglycemia or hyperglycemic
crisis, a random plasma glucose > 200 mg/dL (> 11.1 mmol/L) is
diagnostic.
** In the absence of unequivocal hyperglycemia, results should be conﬁrmed by repeat testing
on a different day.

 OGGT = The test should be performed as described by the WHO, using a glucose load
containing the equivalent of 75 g anhydrous glucose dissolved in water.
 Fasting is defined as no caloric intake for at least 8 hr.
PREDIABETES
Definition:
• Impaired Glucose Tolerance (IGT): 140 < 2-hr PG < 200 mg/dl or,
• Impaired Fasting Glycemia (IFG): 100 < FBS < 126mg/dl or,
• HbA1C: 5.7–6.4%
Why is Prediabetes important?
 Risk For Future Diabetes
 Risk For Macrovascular Diseases
HYPERGLYCEMIA IN PREGNANCY
Hyperglycemia in pregnancy falls in either of the following two categories:
1. Gestational diabetes is defined as:
• Fasting plasma glucose ≥92 mg/dL, but <126 mg/dL in second and third trimesters.
• 75 gram two hour oral glucose tolerance test (OGTT) with at least one abnormal result:
fasting plasma glucose ≥92 mg/dL but <126 mg/dL or one hour ≥180 mg/dL or two
hour ≥153 mg/dL .
– OGTT should be done at 24-28 weeks for pregnant women with risk factors.
2. Overt Diabetes (diabetes mellitus in pregnancy): is made if standard nonpregnant criteria
for DM diagnosis are met at any gestational age.
That is one or more of the following criteria are met: fasting plasma glucose ≥126 mg/dL (7.0
mmol/L), two hour plasma glucose ≥200 mg/dL (11.1 mmol/L) following a 75 gram oral
glucose load, random blood glucose ≥200 mg/dL (11.1 mmol/L) in the presence of diabetes
symptoms.

GLOBAL AND NATIONAL EPIDEMOLOGY OF DIABETES
Diabetes is one of the largest global health emergencies of the 21st century. It is in a state of
global epidemic affecting every country, every age group and every economy across the world.
According to the International Diabetes Federation(IDF) year 2015 estimate, 8.8% of the
world population is having diabetes (it was 4.7% in 1980). Type 2 diabetes is the most
prevalent form of diabetes accounting for more than 91 to 95% of adult with the disease.
Type 2 Diabetes is one of the four major Non-communicable diseases as shown in the table
below. The four risk factors contribute to its increase globally.
Currently, 415 million people aged between 20 and 79 years are estimated to have diabetes,
majority of which (75%) is living in low and middle income countries. This is set to reach 642
million people with diabetes by 2040
In the year 2015, an additional (6.7%) 318 million people have impaired glucose
tolerance(prediabetes) which are at high risk to develop the disease in the future.
In the same year an additional 318 million people (6.7% of adult population) have impaired
glucose tolerance (prediabetes) which are at high risk to develop the disease in the future.
The incidence of type 1 diabetes among children is also increasing in many countries (3%
annually), with total 542,000 children having type 1 diabetes in 2015 across the world.
The proportion of undiagnosed diabetes is 46.5% globally, but varies among countries ,with
highest estimate of 66.7% in Africa
Diabetes and its complications are major cause for early death in most countries, cardiovascular
death being the leading cause in diabetic population.

Diabetes caused 1.5 million direct deaths in 2012. Higher-than-optimal blood glucose also
caused an additional 2.2 million deaths, by increasing the risks of cardiovascular and other
diseases. Forty-three percent of these 3.7 million deaths occur before the age of 70 years.
The Economic burden of diabetes is very huge.
 Catastrophic medical expenditure significantly higher in people with diabetes.
 Direct annual cost of diabetes globally > US$ 827 billion.
 Health spending on diabetes accounted 11.6% of total health expenditure worldwide in
2015
 Losses in GDP worldwide estimated to be US$ 1.7 trillion from 2010 to 2030
The Burden of DM IN AFRICA

In the year 2015 the highest number of diabetes estimated in Sub Saharan Africa was as follows:
• South Africa : 2.3 million,
• Democratic Republic of Congo :1.8 million,
• Nigeria :1.6 million and
• Ethiopia :1.3 million
Nearly half of all adults with diabetes in the region live in these four countries.
The Burden of DM IN ETHIOPIA

Preliminary report from the recently conducted National NCD STEPS Survey showed 6% of
adults had raised blood glucose or diabetes.
International Diabetes Federation estimates for Ethiopia for the year 2015 show:
• The prevalence of diabetes in adults 20-79 years is 2.9%.
• There were over 1.3 million cases of diabetes in Ethiopia in 2015.
• Annually 11,000 men and 10,000 women die from diabetes or raised blood sugar and its
complications in Ethiopia
Reasons for the rise in Prevalence of DM

Some of the reasons for the rise of diabetes globally and in Ethiopia include:
• Increasing Population
• Increasing Age
• Unhealthy Diet
• Sedentary Life Style
• Obesity
• Smoking
• Stress

Prevention of Diabetes Mellitus
The high prevalence of undiagnosed Type 2 diabetes and the proportion of patients with
evidence of complications at diagnosis create a strong imperative for screening.
There are general recommendations for prevention of DM for the general public. However
evidences show that diabetes is more likely to occur in certain patient groups.
Screening is recommended for selected population groups as shown below.
Criteria for testing for diabetes or prediabetes in asymptomatic adults and

children:
1. Testing should be considered in all adults who are overweight (BMI>25 kg/m2 )
and have additional risk factors:
– Physical inactivity
– First-degree relative with diabetes
– Members of a high-risk ethnic population (e.g., African American, Latino, Native
American, Asian American, Pacific Islander)
– Women who delivered a baby > 4kg or diagnosed as GDM
– Hypertension (BP >or = 140/90mmHg or on therapy)
– HDL-C <35 mg/dl and or TG >250 mg/dl
– HbA1c >5.7 %, IGT, or IFG on previous testing
– History of Cardiovascular Disease
– Women with poly cystic ovarian syndrome
2. For all patients, testing should begin at age 45 years.
3. For children age 10yrs and above or at onset of puberty whichever comes first: who are
overweight with any two of the following :
– DM in first or second degree relative
– Signs of insulin resistance (Acanthosis nigricans, severe obesity).
– Gestational Diabetes Mellitus in mother during child’s gestation.
4. If results are normal, testing should be repeated at a minimum of 3-year intervals, with
consideration of more frequent testing depending on initial results (e.g., those with
prediabetes should be tested yearly) and risk status.
The outcome of the screening will be either Normal or Prediabetes or Diabetes.
Once Diabetes is diagnosed the patient should be enrolled to NCD clinic and a formal initial
evaluation using the intake form should be done.
For clients with initial normal tests appointment for repeat test (after 3 years) should be given.
For those clients with initial results showing prediabetes interventions to prevent or delay the
onset of type 2 DM should be instituted because prediabetes will progress to Type 2 DM in
about 50% of individuals over 3 years and it predisposes to macrovascular complications like
coronary heart disease, stroke and peripheral vascular disease.

General Lifestyle Recommendations for Prevention of Type 2 DM
Pharmacotherapy for prevention of Type 2 DM

Metformin therapy for prevention of type 2 diabetes should be considered in those with
prediabetes, especially in those with BMI >35 kg/m2, those aged <60 years, and women with
prior gestational diabetes mellitus.
At least annual monitoring for the development of diabetes in those with prediabetes is
suggested.
Screening for and treatment of modifiable risk factors for cardiovascular disease is suggested.
UNIT 1 SUMMARY
 Diabetes is defined by the World Health Organization (WHO) as a metabolic disorder
characterized by chronic hyperglycemia associated with disturbances of carbohydrate, fat
and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
 Diabetes is diagnosed by laboratory measurement of glucose or glycosylated hemoglobin
level in a blood sample. There are clear criteria for diagnosis.
 Diabetes mellitus is in a state of global epidemic affecting every country, every age group
and every economy across the world.

UNIT 2: CLASSIFICATION AND PATHOGENESIS OF DIABETES MELLITUS
Total Time Allotted for UNIT 2: 1 hour and 30 minutes

LEARNING OBJECTIVES OF THE UNIT
• Be able to classify diabetes based on the pathogenesis (etiology)
• Describe the role of endocrine pancreas in glucose homeostasis.
• Understand the autoimmune mediated pathogenesis the of type 1 Diabetes
• Understand the role of the various factors in the pathogeneses of type 2 Diabetes
INTRODUCTION
Diabetes Mellitus is a metabolic disorder characterized by persistent hyperglycemia
The pancreas plays a central role in glucose, protein and fat metabolism.
Insulin secreted by beta-cells of Islet of Langerhans of pancreas is the major hormone which
controls the level of glucose in blood.
Glucose level in the blood is also influenced by several other hormones
Diabetes mellitus results either from an inadequate secretion of insulin, an inadequate response
of target cell to insulin or combination of these factors
Several other mechanisms including the glucagon level, hepatic glucose production, renal
glucose reabsorption and the incretin hormones play significant role in the pathogenesis
particularly in type two diabetes
THE PANCREAS AND GLUCOSE HOMEOSTASIS

The pancreas has an exocrine part involved in the release of enzymes for the digestive system. It
also contains endocrine cells interspersed in the exocrine acinar tissue called Islets of
Langerhans.
Figure: The endocrine pancreas

a) the islets of Langerhans embedded
in the exocrine acinar tissue
b) islets containing a core of β-cells
surrounded by α- and δ-cells
c) granules secreted by different cells
d) β-cell releasing insulin

The Islets of Langerhans produce several hormones:
1. β-cells: Synthesize Insulin
2. α-cells: producing glucagon,
3. δ-cells: producing somatostatin,
4. ε-cells: producing ghrelin and
5. Pancreatic polypeptide (PP) cells: producing pancreatic polypeptide.
In response to nutrients following a meal, insulin is secreted in a coordinated pulsatile fashion
from the β-cells into the portal vein in a characteristic biphasic pattern
• first there is an acute rapid ‘first phase’ release of insulin, lasting for a few minutes,
• followed by a less intense more sustained ‘second phase’.
Figure: Characteristic Biphasic insulin secretion after meal

Pancreatic β-cells also secrete 0.25–1.5 units of insulin/h during the fasting state(Basal).
Although at a low-level, this background secretion accounts for over 50% of total daily insulin
production.
Glucose is the principal stimulus for insulin secretion, though other macronutrients, and
hormonal and neuronal factors may alter this response.
MAJOR INSULIN ACTION IN GLUCOSE HOMEOSTASIS
 Normal insulin action in different human tissues :
 Muscle tissue  glucose uptake and utilization
 Liver:  glycogen storage, glycolysis; glycogenolysis, gluconeogenesis
 Fat tissue:  synthesis,  lipolysis (ketogenesis)
 The plasma glucose concentration is determined by a balance between glucose entry
from the gastrointestinal tract and hepatic glucose production Vs tissue glucose uptake
and metabolism
19
CLASSIFICATION OF DIABETES
DM is classified on the basis of the pathogenic process that leads to hyperglycemia, as
opposed to earlier criteria such as age of onset or type of therapy.
DM is classified into four general categories:
1. Type 1 diabetes : due to b-cell destruction, usually leading to absolute insulin
deficiency
2. Type 2 diabetes : results from a progressive insulin secretory defect on the background
of insulin resistance
3. Gestational diabetes mellitus (GDM) : diabetes diagnosed in the second or third
trimester of pregnancy that is not clearly overt diabetes.
4. Specific types of diabetes : DM due to specific causes e.g. drug (such as steroid
induced DM)
The Spectrum of glucose homeostasis and diabetes is depicted in the figure below for the
different categories.
Arrows indicate that changes in glucose tolerance may be bidirectional in some types of diabetes
e.g. Type 2 DM and Gestational DM.
CLASSIFICATION OF DM IN AN INDIVIDUAL PATIENT

The etiology of diabetes in an individual with new-onset disease can usually be assigned on the
basis of clinical criteria.
National Training on Diabetes Mellitus 2016 Page 20

The following table shows clinical criteria that may help to classify DM in an individual patient.
Type 1 DM Type 2 DM
1) Onset of disease prior to age 30 years; 1) Onset of disease after the age of 30 years;
2) Lean body habitus; 2) Are usually obese (80% are obese, but
3) Requirement of insulin as the initial elderly individuals may be lean);
therapy; 3) May not require insulin therapy initially;
4) Propensity to develop ketoacidosis; and 4) DKA is rare, and
5) An increased risk of other autoimmune 5) May have associated conditions such as
disorders such as autoimmune thyroid insulin resistance, hypertension,
disease, adrenal insufficiency, pernicious cardiovascular disease, dyslipidemia, or
anemia, celiac disease, and vitiligo. Polycystic Ovarian Syndrome (PCOS).
Some patients cannot be clearly classified as having either type 1 or type 2 DM.
Exception to the above guideline happens frequently i.e. young people developing Type 2 DM
and older individuals developing Type 1 DM.
Also presentation with diabetic ketoacidosis is not necessarily limited to type 1 DM.
Hence difficulties in diagnosis may occur in children, adolescents, and adults, with the true
diagnosis becoming more obvious over time
PATHOGENESIS OF DIABETES MELLITUS

1. Pathogenesis of Type 1 Diabetes Mellitus
• It is characterized by loss of the insulin producing pancreatic beta-cells of islet of
Langerhans
• Sensitivity and responsiveness to insulin are usually normal
• Type 1 DM accounts for less than 10% of the general diabetic population globally
• Type 1 DM affects children and adolescents predominantly but can also occur in adults
• Loss of beta-cells leading to Type 1 DM is caused by an autoimmune destruction i.e.
antibodies directed against insulin and Islet proteins
• ~ 85% of T1DM patients have circulating islet cell antibodies
 Majority also have detectable anti-insulin antibodies
• Most islet cell antibodies are directed against Glutamic Acid Decarboxylase (GAD) within
pancreatic beta cells
• Three main factors are involved in type 1 DM pathogenesis
 Genetic predisposition
 Triggering environmental factor(s)
 Development and progression of auto-Immunity

• Chronic autoimmune disorder occurring in genetically susceptible individuals. It may be
precipitated by environmental factors. Destruction of the insulin secreting cell in the
pancreatic islets takes place over many years.
Figure: Temporal model for development of type 1 diabetes. (Adapted from HPIM 19th ed)
2. Pathogenesis of Type 2 Diabetes Mellitus

• Type 2 DM is a heterogeneous disorder
• It encompasses a range of disorders with common phenotype of hyperglycemia.
• Accounts for more than 90% of diabetic cases in many populations.
• It is characterized by impaired insulin secretion, insulin resistance, increased hepatic
glucose production and abnormal fat metabolism
• Insulin resistance is believed to be an early defect and a root cause in Type 2 DM
• At the time of diagnosis, both impaired insulin secretion and insulin resistance are
already established
• Insulin resistance may be the result of genetic factors, obesity, decreased physical
activity or glucose toxicity
• Insulin resistance in the liver, muscle, and adipose tissue leads to
• increased hepatic glucose production
• decreased glucose uptake in peripheral tissues
• increased lipolysis
• Several other important factors play significant role in the pathogenesis of type 2 DM
including abnormalities involving the glucagon and increin levels and effects
• There is no evidence of immune activation in type 2 DM

Insulin Resistance in Type 2 DM
Type 2 DM is progressive and a continuum

– Insulin resistance leads to a compensatory increase in insulin secretion by the β-cells of the
pancreas (hyperinsulinaemia) in order to achieve normoglycemia
– β-cell function eventually starts to decline, resulting in impaired glucose tolerance (IGT) and
Type 2 DM

– The -cells are also damaged by lipotoxicity and glucotoxicity as a result of insulin
resistance.
– Mean β-cell function is < 50% at diagnosis of Type 2 DM, and keeps deteriorating over the
years as seen in studies.
Other Pathophysiologic changes in type 2 DM

• Decreased incretin effect:
 This is the effect of food on secretion of GIT hormones mainly GLP-1 and GIP
which facilitate insulin secretion. This response is also defective in Type 2 DM.
• Altered glucagon-insulin dynamics in response to meals

 Delayed and suppressed insulin response and failed normal postprandial
decline in glucagon concentrations
 Insulin is not sufficient to drive glucose uptake in the body tissue and the
increased glucagon and decreased insulin cause the liver to inappropriately
release glucose into the blood
 The resultant effect is fasting hyperglycemia or increasing postprandial glucose
• Increased renal glucose re-absorption

Summary of the Pathogenesis of Hyperglycemia in Type II DM (the Ominous Octet)
3. PATHOGENESIS OF GESTATIONAL DIABETES MELLITUS

All women who are pregnant have increasing insulin resistance. Most women are able to
increase the secretion of insulin to overcome the resistance and therefore they do not
experience higher than normal blood glucose levels. β -cells usually make more insulin to
compensate for resistance – when they cannot meet the needs hyperglycemia occur.
Those women who cannot secrete more insulin develop gestational diabetes.
Hyperglycemia in Pregnancy can be
a. Gestational diabetes is defined as:
• Fasting plasma glucose ≥92 mg/dL, but <126 mg/dL in second and third trimesters
• 75 gram two hour oral glucose tolerance test (OGTT) with at least one abnormal result:
fasting plasma glucose ≥92 mg/dL but <126 mg/dL or one hour ≥180 mg/dL or
two hour ≥153 mg/dL .
– OGTT should be done at 24-28 weeks for pregnant women with risk factors.
b. Overt Diabetes (diabetes mellitus in pregnancy): is made if standard nonpregnant
criteria for DM diagnosis are met at any gestational age.
GDM is characterized by β-cell function that is unable to meet the body’s insulin needs. Insulin
resistance begins in mid pregnancy and progresses through the third trimester. It is the result
of maternal adiposity and effects of placental hormones
Most women revert to normal glucose tolerance postpartum but have a substantial risk (35–
60%) of developing DM in the next 10–20 years.

Individuals at higher risk for Gestational Diabetes include:
 Obese women
 Those with previous history of glucose intolerance
 Any pregnant woman who has elevated fasting, or random blood glucose level.
 Those with a history of gestational diabetes mellitus
 Those with a history of large for gestational–age-babies(>4kg)
 First Degree relative with DM
 Maternal age >25 years of age
 Previous unexplained perinatal loss or birth of a malformed infant
Diabetes diagnosed at the initial prenatal visit (early pregnancy) should be classified as “overt”
diabetes rather than GDM.
4. SPECIFIC TYPES OF DIABETES

DM due to specific causes such as :
 monogenic diabetes e.g. maturity-onset diabetes of the young [MODY])
 endocrinopathies like thyrotoxicosis, Cushing’s syndrome
 diseases of the exocrine pancreas (e.g. cystic fibrosis)
 drug or chemical-induced diabetes (steroids, HAART)
UNIT 2 SUMMARY
 Diabetes Mellitus is a metabolic disorder characterized by persistent hyperglycemia
 Type 1 diabetes occurs due to b-cell destruction, usually leading to absolute insulin
deficiency
 Type 2 diabetes results from a progressive insulin secretory defect on the background
of insulin resistance
 Gestational diabetes mellitus (GDM) is hyperglycemia diagnosed in the second or
third trimester of pregnancy that is not clearly overt diabetes.
 Specific types of diabetes : DM due to specific causes e.g. drug (such as steroid
induced DM)

UNIT 3: CLINICAL MANIFESTATIONS OF DIABETES MELLITUS &
MANAGEMENT OF ACUTE COMPLICATIONS
TOTAL TIME ALLOTTED FOR UNIT 3: 3 hours and 30 minutes

UNIT OBJECTIVES
By the end of this UNIT participants will be able to:
• Discuss the clinical manifestations of diabetes with peculiarities of Type 1 and Type 2 DM
• Describe the initial approach in the work up of a newly diagnose diabetic patient.
• Explain the different complications of diabetes.
• Discuss acute complications of DM and their management.
CASE STUDY I
 A 24 yrs old accountant, presented with history of polyurea, polydypsia of 2 weeks duration,
he gives history of weight loss of 3 kgs. On arrival the doctor in the medical OPD evaluated
him and ordered an urgent Blood sugar and Urine analysis. The result appeared after 30
mints showed Random blood sugar of 287 mg/dl and Urine sugar of 2 +, no ketonuria.
QUESTION 1
– What the diagnosis of the patient?
– What additional information do you want to know?
– What additional tests do you want to do?
ANSWER:
CASE STUDY 2
A 47 yrs old , Bank Manger presented with history of profound weakness fatigue, weight loss of
2 months duration. He developed cough, running nose, sneezing and headache of 2 days
duration for this he visited a private clinic in early morning. His physical examination was non-
revealing except he had runny nose and nasal congestion. The lab result revealed, normal CBC,
FBS 178 mg/dl.
QUESTIONS
 What is the diagnosis of this patient?
 How do you confirm the diagnosis?
 What additional information do you want to know?
ANSWER:

CLINICAL MANIFESTATIONS OF DIABETES MELLITUS
Most Type 1 diabetes mellitus and few type 2 diabetic patients usually present with
• Increased thirst and Polydypsia
• Polyuria and nocturia
• Polyphagia
• Unexplained weight loss and
• muscle wasting
• Extreme fatigue
SYMPTOMS AND SIGNS OF TYPE I DM
However about half of type 2 diabetes patients may remain asymptomatic or might have non -
specific symptoms. Because of this more than 50% of type two diabetic patients remain
undiagnosed.
Some type 2 DM patients can present with chronic complications of diabetes mellitus.
Other features of DM are
 Blurred vision,
 Recurrent skin infections,
 Recurrent itching of the vulva,
 Abnormal sensory/ motor neurologic findings on extremities,
 Foot abnormalities (various deformities, ulcers, and ischemia) could be a presenting
signs.
 Symptoms and Signs of Acute complications

COMPLICATIONS OF DIABETES
Diabetes or its treatment can cause acute complications or long term complications called
chronic complications:
a) Acute
• Diabetic Ketoacidosis (DKA)
• Hyperglycemic Hyperosmolar State (HHS)
• Hypoglycemia - Complication Of Treatment
b) Chronic
DIAGNOSTIC CRITERIA FOR DM
NB:
• Fasting is defined as no caloric intake for at least 8 hr
• ** Repeat test needed on a different day

INITIAL EVALUATION OF A PATIENT NEWLY DIAGNOSED WITH DIABETES
MELLITUS
Once the diagnosis of DM is made an initial evaluation should be made to:
 Classify the diabetes
 Detect the presence of diabetes complications
 Review previous treatment and glycemic control in patients with established diabetes
 Assist in formulating a management plan
 Provide basis for continuing care.
The history and physical examination should assess for symptoms or signs of acute
hyperglycemia and should screen for the chronic complications and conditions associated with
DM.
MEDICAL HISTORY
A complete medical history should be obtained with special emphasis on
– DM-relevant aspects such as weight, family history of DM and its complications, risk
factors for cardiovascular disease, exercise, smoking, and ethanol use.
– Symptoms of hyperglycemia include polyuria, polydipsia, weight loss, fatigue, weakness,
blurry vision, frequent superficial infections (vaginitis, fungal skin infections), and slow
healing of skin lesions after minor trauma.
– In a patient with established DM, the initial assessment should also include special
emphasis on prior diabetes care, including the type of therapy, prior HbA1c levels, self-
monitoring blood glucose results, frequency of hypoglycemia, presence of DM-specific
complications, and assessment of the patient’s knowledge about diabetes, exercise, and
nutrition.
– Diabetes-related complications may afflict several organ systems, and an individual
patient may exhibit some, all, or none of the symptoms related to the complications of
DM .
– In addition, the presence of DM-related comorbidities should be sought (cardiovascular
disease, hypertension, dyslipidemia).
– Pregnancy plans should be ascertained in women of childbearing age.
PHYSICAL EXAMINATION
A comprehensive physical examination should be done with special emphasis on
• Height, weight and BMI, waist circumference
• Blood pressure determination, including orthostatic measurements when indicated
• Thyroid palpation
• Skin examination for Acanthosis nigricans, infections, insulin injection sites

• Neurologic exam
• Fundoscopic examination
• Comprehensive foot exam (Use the 60 second screening tool attached in Annex 6)
– Inspection
– Palpation of dorsalis pedis and posterior tibial pulses
– Presence/ absence of patellar and Achilles reflexes
– Determination of proprioception, vibration and monofilament sensation
CALCULATE BMI AND CLASSIFY AS FOLLOWS

Body Mass Index (BMI) = Weight (in kg)/[Height (in m)]2
Nutritional Status BMI (Kg/m2)
Underweight < 18.5

Ideal Weight 18.5 - 24.9
Overweight 25 - 29.9
Obese 30-39.9
Morbid Obese >40
WAIST CIRCUMFERENCE
• Normal
– Males <94 cm
– Females <80 cm
• Measure midway between lower costal margin & iliac crest as shown in the picture below.

LABORATORY EVALUATION
The laboratory assessment should first determine whether the patient meets the diagnostic
criteria for DM and then assess the degree of glycemic control. Some of the lab tests that should
be done are listed below
For confirming diagnosis
• FBS
• RBG
• HgA1C
Other lab evaluations
• Liver function tests
• Fasting lipid profiles
• Serum Creatinine
• TSH in patients with type 1 diabetes or dyslipidemia or women aged > 50 years
• Urine analysis to check for Protienuria, ketonuria, glucosuria, Casts, urinary tract
infection.
Referrals for initial care management
Diabetic patients may need evaluation and care by different health professionals.
• Eye care professional for annual dilated pupil eye exam.
• Family planning for women of reproductive age.
• Preconception care for women
• Dentist for comprehensive dental and periodontal examination.
• Mental health professional, if indicated.

ACUTE COMPLICATIONS OF DIABETES MELLITUS
The commonest and more serious acute complications of diabetes are
1. Diabetic Ketoacidosis (DKA)
2. Hyperglycemic Hyperosmolar State ( HHS)
3. Hypoglycemia
CASE STUDY 3
A 28 yrs old Type 1 Diabetic who has been on NPH insulin 22 IU, am and 12 IU, pm, SC.
developed cough, chest pain and fever of four days duration. These symptoms were
accompanied by polyuria , polydypsia , vomiting and abdominal pain of two days duration.
On Physical Examination: Patient has deep breathing, is confused,
B/P, : 80/50mmHg, pulse 124/minute,Temp.38,6oC.,
He has sunken eye balls and Bronchial breath sounds in the Left lower posterior lung field.
QUESTIONS
 What are the Diagnoses of the patient?
 How do you confirm the diagnosis?
ANSWER:
Lab results of the Patient were:

 RBS =450 mg/dl,
 Urine sugar = 4+,
 Urine ketone = 3+,
 CXR: Homogenous opacification in the left lower lung field
QUESTIONS
– Is there a change in your diagnosis?
– How would you manage this patient?
ANSWER:

DIABETIC KETOACIDOSIS and HYPERGLYCEMIC HYPEROSMOLAR STATE
DKA and HHS are very serious DM complications with overlapping features resulting from
relative or absolute insulin deficiency and if left untreated both are life threatening. However
both conditions are preventable and treatable.
DIABETIC KETOACIDOSIS
Introduction:
Diabetic ketoacidosis (DKA) is a condition in which there is a severe deficiency of insulin
resulting in very high blood glucose which nonetheless is unavailable to the body tissues as a
source of energy.
Fat is therefore broken down as an alternative source of energy with ketones/ketoacids as a by-
product.
This state of severe hyperglycemia and ketone body production results in severe metabolic,
fluid and electrolyte abnormalities.
It often occurs in type 1 diabetes patients but may also occur in type 2 diabetes.
It is characterized by:
 hyperglycemia (BG>250mg/dl)
 ketosis (urine ketone >/= 2+) and,
 acidosis
The precipitating factors of DKA include:
– previously undiagnosed and untreated diabetes,
– Insulin errors, omissions and non-adherence
– stress of Intercurrent illness (e.g., Pneumonia, meningitis, UTIs, Acute Febrile Illnesses,
Trauma, myocardial infarction, stroke, surgery, etc)
– Drugs e.g. steroids, cocaine
– Pregnancy
– psychological stress
– no precipitant factors could be found in up to 20-30% of cases
CLINICAL FEATURES OF DKA:

Clinical features may include worsening poly symptoms like Hunger, excessive urination,
excessive thirst and, excesive drinking of water.
Non specific symptoms like malaise, fatigue, nausea, vomiting, abdominal pain (may mimic
acute abdomen)
Signs of dehydration may ensue fast with dry skin, reduced skin turgor or sunken eyes.The
blood pressure may drop and the pulse becomes fast and weak .

Symptoms of infection or other underlying condition may be seen
Signs and symptoms of acidosis and ketosis may manifest,
– deep and fast breathing (Kussmaul Breathing), and
– 'Fruity' breath (smell of acetone).
Altered level of consciousness (depressed mentation to coma) could be a feature of severe DKA.
If you find such clinical features :
Do
• Serum/finger prick glucose
• urine analysis – ketones , glucose, leucocytes
• Complete blood count
• pregnancy test in women of child bearing age
• others tests as per the clinical indications
In Primary and General Hospitals
• Serum electrolytes (K, Na),
• renal function,
In Tertiary Hospitals
• blood gas analysis ,
• calculation of anion gap and serum osmolality should be done.
Diagnosis of DKA is confirmed:

 Based on clinical symptoms and signs and
 RBS > 250 mg/dl
 Positive Urine ketone (2+ and above)
 Glucosuria
MANAGEMENT OF DKA AND HHS. See Algorithm III

1. Attention to ABC immediately on arrival !!!
2. Correct fluid deficit
The fluid deficit in in DKA often 3 to 5 liters but in HHS it is up 10 liters or more .
Types of fluid to administer:
– start with 0.9 % N/S
– later may change to 0.45% saline, if available, when serum sodium is normalized
– once Blood Glucose reaches ≤ 250 mg/dl change IV fluid to 5 % dextrose
– Initial fast hydration (1-2 lit. in the 1st hr) then based on response. Follow the
hydration status, urine out put and serum electrolytes. Avoid fluid overload.
– Generally replace 50% of total deficit in 8 hrs, the rest in 16 hr

3. Insulin
– IV infusion of regular insulin (for mild DKA IV Q 1hr after an IV- and IM bolus 10 IU
each)
– Postpone insulin Rx if hypotensive or hypokalemic .
– doses: 0.1 IU/kg/hr with initial bolus of 0.1-0.15IU/kg
– let 50 ml fluid through the line before starting infusion
4. Correct Potassium deficits
The Goal of therapy of DKA is to lower blood glucose by 50-75mg/dl/hr. If target not achieved
increase the hourly insulin dose by 50%. If blood glucose falls below 250mg/dl shift to 5% D/W
and decrease hourly insulin dose by 50%. Continue infusion until ketones clear. Keep Blood
Glucose between 150 & 250 mg/dl. When ketone clears shift to standing NPH Insulin S.C with
additional hourly Regular insulin based on Blood glucose for 2 hrs.
CASE STUDY 4
A 67 yrs. old male patient from Debrebirhan, known case of diabetes mellitus for the last 25 yrs,
on Glibenclamide of 5mg Bid, presented with history of pain and Ulceration of Rt. foot of one
month duration. These symptoms were accompanied by polyurea, polydypsia weakness and
vomiting. On Examination patient was comatose, BP: 90/60 mmHg, temp, 36.8oc, ulcerated rt.
Foot, with purulent discharge. His RBS was > 600 mg/dl.
QUESTION
 What are the specific diagnoses of this patient?
 How would you manage this patient?
ANSWER:
HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS)

It is less common than DKA, but results in more death than DKA because it mainly affects the
elderly and those with co – morbidity. It occurs in type 2 diabetes mellitus. It progresses
relatively slowly. The major features are
– severe hyperglycemia (often>600mg/dl)
– Profound dehydration.
Management of HHS (See Algorithm no. III)
Management of HHS is similar to the management of DKA but fluid replacement is usually
much higher (up to 8- 10 liters). Potassium replacement is not usually needed unless indicated
by low serum potassium level.

CASE STUDY 5
A 75 yrs. Old , Known case of Type 2 diabetes patient, who has been taking, Glibenclamide 10
mg BID, recently developed decreased appetite because of lower abdominal pain, he suddenly
developed profound weakness, palpitation sweating and became unconscious.
Questions
 What is the most like diagnosis of the patient?
 How would you confirm the diagnosis?
 What will you do for the patient?
Answer:
HYPOGLYCEMIA
Hypoglycemia is defined as blood sugar values ≤ 70 mg/dl.

Hypoglycemia occurs in most patients with type 1 diabetes and some type 2 diabetics.
Hypoglycemia can cause serious morbidity; if severe and prolonged, it can be fatal. Most
common risk factors for hypoglycemia are
• fasting or missed meals
• insufficient meals
• overdose of hypoglycemic agents or insulin
• exercise
• chronic kidney disease,
• hepatic disease
• other drugs and alcohol consumption
CLINICAL MANIFESTATIONS OF HYPOGLYCEMIA

Clinical presentations of hypoglycemia may be associated with Autonomic manifestations
(“You are hungry”) like Anxiety, Tremulousness, palpitations, sweating, hunger and
Paresthesias ; and Neuroglucopenic manifestations(“Your nerves are hungry”) which
includes headache, Extreme Fatigue, Confusion, Seizure, drowsiness, lethargy and coma as the
hypoglycemia deepens.
Remember that some patients who develop frequent hypoglycemia may lose the warning signs
of hypoglycemia (hypoglycemia unawareness)
DIAGNOSIS OF HYPOGLYCEMIA
When such symptoms happen in a diabetic patient hypoglycemia should be suspected and blood
should be drawn immediately to determine blood sugar level and urgent correction should
begin.

To prevent future recurrence the cause of the hypoglycemia should be looked for and corrected
and the patient and family should be educated how to avoid hypoglycemia and treat it at home
while seeking medical help.
MANAGEMENT OF HYPOGLYCEMIA (SEE ALGORITHM NO. IV)

Hypoglycemia is a medical emergency
– do not wait for confirmation if test is not readily available
– change in mental status in a diabetic is considered to indicate hypoglycemia until proven
otherwise !!!
If the patient is able and willing give oral treatment with table sugar solution, mirinda, other
glucose-containing fluids, 3-4 candy bars, or food is appropriate. A reasonable initial dose is 20
g of glucose. Forceful attempt to give glucose by mouth in a stuporous or disoriented individual
is difficult and may prove harmful – avoid this!!
If the patient is unable or unwilling (because of neuroglycopenia) to take carbohydrates orally,

IV administration of 50ml of 40% dextrose (~25 g) should be followed by a 10% glucose
infusion guided by serial plasma glucose measurements. Start oral feeding as soon as possible.
UNIT 3 SUMMARY
Most Type 1 diabetes mellitus and few type 2 diabetic patients usually present with polydypsia,
polyuria, polyphagia, weight loss and muscle wasting.

UNIT 4: CHRONIC COMPLICATIONS OF DIABETES MELLITUS
LEARNING OBJECTIVES
By the end of this UNIT the participants will be able to:
• Discuss Follow up care of DM for early identification and management of complications
• To understand the most common chronic complications of Type 1 & Type 2 DM
• Explain Common presentations of the common chronic complications
• To know screening specifics(who, when and how)
• To know how to manage common complications.
• To know which patients to refer for further Management
CLINICAL MONITORING IN DIABETES CARE

What are the Aims of Clinical Monitoring?
– Glycemic control
– Identification and control of associated risk factors
– Assessment of adherence
– Psychosocial assessment
– Prevention, Identification and treatment of chronic complications
Tools in Clinical Monitoring
a. Medical History
– Diabetes education history
– DKA frequency, severity, and cause
– Hypoglycemic episodes
– Current treatment
• Medications, meal plan, physical activity patterns and results of glucose monitoring
– Adherence to treatment
b. Physical examination
• Weight, BMI, waist circumference
• B/P including orthostatic measurement, when indicated
• Fundoscopic examination
• Comprehensive foot examination
– Inspection
– Palpation of dorsalis pedis and posterior tibial pulses
– Presence/absence of patellar and Achilles reflexes
– Determination of proprioception, vibration, and monofilament sensation

c. Glycemic control
i. Self Monitoring of Blood Glucose (SMBG)
– Ideally the Standard Of Care in DM management
– Frequency and targets dictated by particular needs and goals of patient
– Very important for patients treated with insulin, Type 1 patients and pregnant women
– Helps prevent asymptomatic hypoglycemia and hyperglycemia
– Recommendation is > 3X a day in Type 1 and 2 on multiple Insulin injection
– No consensus on frequency for type 2 patients
ii. Fasting Blood Glucose (FBG)
– Tells short term glucose level
– When combined with postprandial plasma glucose level measurement it is the best
alternative to HBA1C measurement.
iii. Glycosylated Hemogloin Level (HbA1C)
– Tells about the glucose level over months (2-3 months)
– Has similar relation with chronic complications with FPG and 2h postprandial glucose
– At least 2x a year for patients who meet treatment goal
– Quarterly in patients whose therapy has changed or who are not meeting glycemic goals
iv. 2hr Postprandial glucose
– More useful in Monitoring Glycemic Control in pregnant mothers.
v. Urine Ketone/Serum Ketone
– Early indicators of DKA
– Should be measured when plasma glucose is persistently above 300mg/dl, during
concurrent illnesses, or with symptoms such as nausea, Vomiting, or abdominal pain
vi. Glucosuria
– Poor means of assessment
– May be the only tool available in some setups and hence may use it short of other tools.
d. Treatment goals for DM
The ideal Glycemic target for adults is as follows
• HB A1c <7%
• Pre-prandial(capillary plasma) 80-130mg/dl
• Postprandial G(capillary plasma) <180mg/dl

INTRODUCTION TO CHRONIC COMPLICATIONS OF DM
Diabetes-related complications affect many organ systems and are responsible for the majority
of morbidity and mortality associated with the disease.
Diabetes-related complications usually do not appear until the second decade of hyperglycemia.
Because type 2 diabetes mellitus (DM) often has a long asymptomatic period of hyperglycemia
before diagnosis, many individuals with type 2 DM have complications at the time of diagnosis.
Fortunately, many of the diabetes-related complications can be prevented or delayed with early
detection, aggressive glycemic control, and efforts to minimize the risks of complications.
Diabetes-related complications can be divided into vascular and nonvascular complications

and are similar for type 1 and type 2 DM.
1) The vascular complications of DM are further subdivided into
– microvascular (retinopathy, neuropathy, nephropathy) and
– macrovascular complications (coronary heart disease [CHD], peripheral arterial disease
[PAD], cerebrovascular disease).
2) Nonvascular complications include gastroparesis, infections, skin changes, periodontal
disease, and arthropathy and hearing loss.
CASE STUDY 1
F.G. is a 35 yrs old female known type 1 diabetic patient on NPH 40/28 Units SC AM/PM. She
came for regular follow up. Her old patient chart could not be found.
Her FBS was 220mg/dl & HBA1C was 8.5%
QUESTION:
What further history do you wish to know?
ANSWER:
FURTHER CLINICAL DATA INDICATED:

The Patient is diabetic for the last 30 years and she takes her medication regularly as
prescribed. Her FBS is usually >200mg/dl for the past 05 years & postprandial glucose is
between 250 & 300mg/dl. Currently on presentation she complains of dysuria, frequency of
urination & urgency but no hypoglycemic episodes. She has no visual complaints – but was told
to have some early changes on routine retinal screening. She has no foot ulcer & no symptoms of
peripheral neuropathy. She rotates her insulin injection sites and has no indurations on
examination. She stores her insulin in the refrigerator.
QUESTION:
How will you investigate this patient?
ANSWER:

Her lab results came:
 CBC- Normal
 U/A – Glucose - ++
Protein - +++
Ketone - negative
Leukocyte & nitrite –both positive
WBC - 10-15/ HPF
Epithelial cells – Many/LPF
How will you treat this patient?
ANSWER:
Follow up data 2 weeks later

 U/A-
– Proteinuria - ++
– No WBC & RBC
– Leukocytes & Nitrites – both negative
How will you proceed?
ANSWER:
I. DIABETIC NEPHROPATHY
• Diabetic nephropathy is the leading cause of Chronic Kidney Disease(CKD) and End Stage
Renal Disease(ESRD).
• Albuminuria in individuals with DM is associated with an increased risk of CVD
• Patients with nephropathy commonly have retinopathy
• An important marker of increased cardiovascular risk. It carries a mortality rate ~50%
from Cardio Vascular causes.
• Its pathogenesis is related to chronic hyperglycemia
• Occurs in 20-40% of diabetic patients
• Type 1: 10-20 years after initial diagnosis
• Type 2: May even be present at time of diagnosis (long pre-clinical period)
• Usually progresses from albuminuria to overt CKD
• Intervention at the stage of Microalbuminuria can retard the progression to end-stage
renal disease
PATHOPHYSIOLOGY OF DIABETIC NEPHROPATHY
• Hyperglycemia is necessary for the development of the lesions of diabetic nephropathy
and also to sustain the lesions.

• Hemodynamic mechanisms may also be involved. Hyper filtration modulates the rate of
progression of diabetic lesions. Systemic BP levels are also implicated in progression.
• Genetic predisposition to or protection from diabetic nephropathy appears to be the
most important determinant of diabetic nephropathy risk.
ALBUMINURIA
Defined and staged by level urinary albumin excretion
STAGES OF CKD
DIABETIC NEPHROPATHY SCREENING

 Screen for albuminuria
 Type 1: 5 years after diagnosis
 Type 2: At the time of diagnosis
 In every pregnant lady
 Thereafter, screening should be done yearly
 Measure serum creatinine at least yearly
 Refer to Internist / Nephrologist patients with persistent proteuinuria and/or deranged
RFT .

SCREENING ALGORITHM FOR ALBUMINURIA IN DIABETES MELLITUS
PREVENTION OF DIABETIC NEPHROPATHY

Intensive glycemic control shown to prevent microvascualr complications including Diabetic
Nephropathy in both type1&2 diabetes. The lowest possible HbA1c is the target.
Treatment of hypertension is of paramount importance in the prevention of Diabetic
Nephropathy. Life style modifications particularly cessation of smoking must be encouraged.
The above measures also reduce CV morbidity and mortality substantially.
TREATMENT: DIABETIC NEPHROPATHY

Improved Glycemic control. Strict blood pressure control is effective in reducing albumin
excretion and slowing the decline in renal function. Blood pressure should be maintained at
<140/90 mmHg in diabetic individuals. Administration of an ACE inhibitor or ARB.
Dyslipidemia should also be treated. Cessation of smoking
CASE STUDY 2:
M.T. is a 60yrs old male presented to ER with history of Rt. toe ulceration of 15days duration. He
was on treatment (cloxacillin & wound care) at nearby clinic but there was no much change. He
complains of numbness of lower limbs with burning & tingling sensation. He has history of HTN
diagnosed 5yrs back but was not on any antihypertensive
Questions:
What additional information do you need?
Answer:
Case 2 (Continued)….

 Patient claims he had mild trauma to the feet while walking with sandals.
 But wound was noticed by child as he has difficulty of vision
 He has mild pain and there is a pussy discharge from the wound
 No history of diabetes.
 He did not take antihypertensives as he did not want his body to “adapt” to the
medication
 He has no SOB on exertion.
Question:
What are the possible diagnoses and how do you like to work her up?
Answer:
CASE 2 CONTINUED:
 Physical Exam
– BP – 150/95mmHg
– Bilateral cataract & loose upper front incisors
– Shiny, dry, cracked, lower limbs with loss of hair
– Rt. 1st digit well circumscribed 2x2cm ulceration & whitish discharge, tenderness not as
marked as size of wound.
– All peripheral pulses are palpable.
– Decreased sensation (on monofilament test)
 Investigation results
– WBC- 14,000 N-85%, L-15%
– Hgb-15g/dl
– Platelet – 250,000
– U/A – protein 1+ and glucose 2+
– FBS – 180mg/dl repeat 198mg/dl
– Cr– 1.4mg/dl
– Retinal screening – Background retinopathy
– ECG – non revealing
– X-ray of the foot: Non-revealing
– Lipid profile
 Total Cholesterol – 270mg/dl
 LDL – 150mg/dl
 HDL – 35mg/dl
 Triglyceride – 172mg/dl

QUESTIONS:
1. List the final Diagnosis
2. How would you manage this patient? (Answer this at the end of the UNIT)
II. DIABETIC NEUROPATHY

 Most common of the chronic DM complications
 Occurs in ~50% of individuals with long-standing type 1 & type 2 DM
 Impairs quality of life
 As with other complications, development of neuropathy correlates with duration of DM
& glycemic control. Other risk factors are obesity, hypertension, smoking , alcohol use
and dyslipidemia.
 Most important risk factor for foot ulcer and amputation
 Clinical evaluation for diabetic neuropathy includes detailed history on symptoms like
burning , tingling and pains; Erectile dysfunction in men; glycemic control; presence
other risk factors , and detailed neurologic exam especially sensory,reflex and motor
exam of the extremities.
 May manifest as polyneuropathy, mononeuropathy, and/or autonomic neuropathy
a. DISTAL SYMMETRIC POLYNEUROPATHY
 Commonest type of diabetic neuropathy.
 Distal symmetric sensory or sensorimotor neuropathy
  pain sensation and vasculopathy  ulcer risk
 Patients complain of numbness, tingling, sharpness, or burning that begins in the
feet / hands & spreads proximally
 Pain is present at rest and worsens at night.
 Physical examination reveals sensory loss, loss of ankle deep-tendon reflexes, and
abnormal position sense
 It is a diagnosis of exclusion
b. AUTONOMIC NEUROPATHY
– Individuals with long-standing type 1 or 2 DM may develop signs of autonomic
dysfunction
– DM-related autonomic neuropathy can involve the cardiovascular,
gastrointestinal, genitourinary, sudomotor, and metabolic systems.
– Autonomic neuropathies affecting the cardiovascular system cause a resting
tachycardia and orthostatic hypotension. Reports of sudden death have also been
attributed to autonomic neuropathy.

– Gastroparesis and bladderemptying abnormalities are often caused by the
autonomic neuropathy seen in DM.
– Hyperhidrosis of the upper extremities and anhidrosis of the lower extremities
result from sympathetic nervous system dysfunction. Anhidrosis of the feet can
promote dry skin with cracking, which increases the risk of foot ulcers.
– Autonomic neuropathy may reduce counterregulatory hormone release (especially
catecholamines), leading to an inability to sense hypoglycemia appropriately
c. DIABETIC POLYRADICULOPATHY
– It is a syndrome characterized by severe disabling pain in the distribution of one or
more nerve roots. It may be accompanied by motor weakness.
 Intercostal or truncal radiculopathy causes pain over the thorax or abdomen.
 Involvement of the lumbar plexus or femoral nerve may cause severe pain in the
thigh or hip and may be associated with muscle weakness in the hip flexors or
extensors (diabetic amyotrophy).
– Fortunately, diabetic polyradiculopathies are usually self-limited and resolve over
6–12 months.
d. MONONEUROPATHY
– It is dysfunction of isolated cranial or peripheral Nerves.
– It is less common than polyneuropathy in DM
– It presents with pain and motor weakness in the distribution of a single nerve.
o Carpal tunnel syndrome….
o Involvement of the third cranial nerve is most common and is heralded by
diplopia. Physical examination reveals ptosis and ophthalmoplegia with
normal pupillary constriction to light.
o Sometimes other cranial nerves, such as IV, VI, or VII (Bell’s palsy), are
affected.
TREATMENT OF DIABETIC NEUROPATHY

o Improve glycemic profile
o May use analgesics initially
o Tricyclic antidepressants – amitriptyline 25mg po nocte – may increase dose gradually
o Carbamazepine 200mg po nocte & increased gradually
o Refer to neurologist
III. DIABETIC FOOT ULCERS
• Major Cause of Hospital Admission in diabetes
• Leading cause of non traumatic lower extremity amputation

• Major Causes of foot ulcer–
– Trauma in Neuropathy &/or
– Peripheral Arterial Disease
– Infection – Not Primary Cause
• Infection is Secondary to Ulceration of Protective Epidermis
• 15% of Diabetics Develop it at Some Time
• Typical Places:
– Plantar Surface of the Great Toe
– Heads of Metatarsals
– Lateral margins due to ill fitting shoe
RISKS FOR FOOT ULCERATION

The following factors increase the likelihood of diabetic foot ulcers.
• Long duration of diabetes
• Peripheral Neuropathy: Somatic & Autonomic
• Peripheral Vascular Disease
• Foot Deformity - Claw Toes, Hammer Toes
• Presence of Callus
• Previous Foot Ulcers
• Poor diabetes control
• Poor Sight
• Male sex
• Old age
EVALUATION FOR THE FOOT AT RISK
• Look for Peripheral Arterial Disease
– Symptoms :Intermittent Claudication, Cold Feet, Nocturnal Pain, Rest Pain, Pain
Relieved with Dependency or rest,
– Signs: Absent Pulses, Blanching On Elevation, Delayed Venous Filling After
Elevation, Loss Of Hair On Foot & Toes, Gangrene
– Doppler studies
• Look for Neuropathy
– Tuning Fork
– Monofilament
• Anatomic Deformities
– Charcot’s Foot
– Hammer Toes

– Clawed Toes
– Callus
PREVENTION DIABETIC FOOT DISEASE
Patient education should emphasize
(1) careful selection of footwear,
(2) daily inspection of the feet to detect early signs of poor-fitting footwear or minor
trauma,
(3) daily foot hygiene to keep the skin clean and moist,
(4) avoidance of self-treatment of foot abnormalities and high-risk behavior(e.g., walking
barefoot), and
(5) prompt consultation with a health care provider if an abnormality arises.
Classification and management of Diabetic Foot Lesions (Wagner 1983)
Grade Description Management
0 High Risk Foot, No Ulcer Education about foot care

Present
1 Superficial Ulcer Relief of Pressure

Treatment of Infection: PO antibiotics
2 Deep Ulcer + cellulitis; Relief of Pressure, Clean and debride wound

but no abscess or bony Treatment of Infection: PO antibiotics
involvement
3 Infected Ulcer with Bony Admit to Hospital

Involvement or abscess Clean and debride wound
formation Initiate Triple IV antibiotics
4 Localized Gangrene (toe, Treat Like Grade 3

forefoot, hill) Improve Circulation
Diffuse Arterial Disease May Require Major
Amputation
5 Gangrene of the whole Urgent Hospital Admission

foot Antibiotics
Amputation
IV. DIABETIC RETINOPATHY

 Common microvascular complication:
 Type 1: Mostly occurs after 15-20 years
 Type 2: Often present at diagnosis (long pre-clinical period)
 The leading cause of adult-onset blindness
 Diabetes also ↑ risk of glaucoma & cataracts

 Fundamental defects in retinopathy:Vascular leakage & neovascularization
Types of Lesions of Diabetic Retinopathy
a. Non (pre-)proliferative retinopathy
 Abnormal vessels within retina
o Basement membrane thickening
o Microaneurysms
 Macular edema, lipid exudates
 Intraretinal angiogenesis
b. Proliferative retinopathy
 Neoangiogenesis
 Vitreous/preretinal hemorrhage
 Retinal detachment
DIABETIC RETINOPATHY SCREENING
 Screening
 Type 1: After 5 years of diagnosis
 Type 2: At time of diagnosis
 Pregnant ladies
 Thereafter, screen annually
 Positive findings should be referred to ophthalmologists for confirmation, monitoring and
LASER Treatment
CASE STUDY 2 REVISITED: Now answer Case 2 Questions above
QUESTIONS: 1
1. List the Final Diagnoses of the patient
2. How would you manage this patient?
ANSWER:
UNIT 4 SUMMARY
 Diabetes-related complications affect many organ systems and are responsible for the
majority of morbidity and mortality associated with the disease.
 Diabetes-related complications usually do not appear until the second decade of
hyperglycemia.

UNIT 5: MANAGEMENT OF TYPE 1 DIABETES MELLITUS

UNIT OBJECTIVES:
By the end of this UNIT trainees will be able to:
– Describe Goals of Type 1 DM Management
– Describe comprehensive management of type 1 DM
– Understand the different types of insulin and their use
– List the different regimens of insulin therapy
– Explain the different complications of insulin therapy
– Describe the basic use of insulin.
– Understand and manage potential complications of Insulin therapy
– Explain the basics of insulin use.
INTRODUCTION TO TYPE I DM
TYPE 1 DIABETES:
• Affects children, adolescents, or young adults (usually < 30 yrs of age)
• Patients are usually not obese.
• First diagnosis may be during an episode of diabetic ketoacidosis.
• Characterized by absolute insulin deficiency due to destruction of beta cells.
• Patients have lifetime dependence on exogenous insulin administration for survival.
• Clinical diabetes occurs when 80-90% of islet cells are destroyed.
• Constitutes 10% of all cases of diabetes.
GOALS OF TREATMENT OF TYPE 1 DM

1. Decreasing plasma glucose levels and urine glucose excretion to eliminate symptoms
2. Prevent diabetic ketoacidosis and severe hypoglycemia
3. Inducing positive nitrogen balance to restore lean body mass and physical capability and
to maintain normal growth, development, and life functioning
4. Preventing or greatly minimizing the late complications of diabetes
MANAGEMENT COMPONENTS
• Patient and family education
• Setting targets
• Diet
• Exercise
• Reduction of risk factors
• Daily monitoring of blood glucose

• Use of Insulin – human and analogs
PATIENT and FAMILY EDUCATION
• Cornerstone of therapy
• Should be Lifelong
• Step by step
• Components of diabetes education
– Causes of diabetes
– Symptoms and signs of diabetes
– Components of its management: Insulin injections diet, etc
– Self-care (with adequate emphasis on oral hygiene and foot care, SMBG )
– Acute complications: hypoglycemia, ketoacidosis, infections
– Chronic complications
DIETARY MANAGEMENT
• Individualize
• Assess Dietary Habits
• No one diabetic diet for all
• Avoid Simple Sugars
• High CHO
• Low Fat
• High Fibre
• Fruits and Vegetables
PHYSICAL EXERCISE
• Important component of diabetes care
• Helps maintain
– cardiovascular conditioning
– insulin sensitivity
– general well-being
• Patients need education on how to adjust their meals, their insulin doses and timing, or
both to prevent hypoglycemia before, during, and after exercise
• High-impact sports are contraindicated for patients with
– advanced retinopathy who are at risk for vitreous hemorrhage
– peripheral neuropathy or vascular disease who are at risk for foot trauma
• Aerobic, Stretch, Strength Exercises
• > 5 times per week for 30-60 min each day

BENEFITS OF INTENSIVE THERAPY (DCCT Trial Outcome)
• Intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by
35% to 90% compared with conventional treatment
• Absolute risks of retinopathy and nephropathy were proportional to the HBA1C level.
• Intensive treatment was most effective when begun early, before complications were
detectable
• Risk reductions achieved at a median A1C 7.3% for intensive treatment (vs 9.1% for
conventional)
• Benefits of 6.5 years of intensive treatment extended well beyond the period of most
intensive implementation (“metabolic memory”)
INTENSIVE TREATMENT SHOULD BE STARTED AS SOON AS IS SAFELY POSSIBLE AFTER THE

ONSET OF T1DM AND MAINTAINED THEREAFTER.
INSULINS
Two types of insulin are currently in use:
– Standard Human Insulin
– Insulin Analogues
Duration of Action of Standard Insulins and Insulin Analogues
PHARMACOKINETICS OF INSULIN PRODUCTS

Insulin analogues are produced by genetic modification of human insulin which made them to
be absorbed easily and rapidly distributed in the blood as shown in the pictures below.

Figure: Dissociation & absorption of insulin after Subcutaneous (SQ) injection
Adapted from Hirsch I. N Engl J Med. 2005;352: 174-183.
Figure: Approximate Pharmacokinetic Profiles of Human Insulin and Insulin Analogues. The
relative duration of action of the various forms of insulin is shown. The duration will vary widely both
between and within persons.
Commonly available commercial insulin products are shown in the following tables
HUMAN INSULINS

INSULIN ANALOGUES
INSULIN REGIMENS
– Basal Regimen
o Twice daily NPH insulin alone
– Bi-Phasic Regimen (Mixed-Split)
o Premixed or Mixed Insulin
– Basal-Bolus Regimen (Intensive Insulin Therapy)
o Prandial insulin + Basal insulin
a) BASAL STANDARD (CONVENTIONAL) REGIMEN

– Intermediate acting insulin twice per day
– With or Without Short-acting Insulin
– Once daily dose is no more acceptable
– BID dosing recommended even for a small dose.
– Commonly used in Ethiopia
b) CLASSICAL “SPLIT-MIXED” TREATMENT PROGRAM

This regimen is simple and has only two injections per day. Its disadvantage is it may
predispose to nocturnal hypoglycemia (from midnight to 4:00 a.m.) and early morning
hyperglycemia (from 4:00 to 8:00 a.m); due to the Dawn Phenomenon.
c) IDEAL INSULIN REPLACEMENT THERAPY

The ideal insulin replacement therapy is Basal/Bolus Insulin regimen which consists of injection
of a long acting or intermediate acting insulin (Basal) given in combination with multiple
injections of a rapid acting insulin (Bolus).
Basal/Bolus Insulin Regimen Concept
• Basal Insulin – intermediate/ long-acting insulins
– Nearly constant day-long insulin level
– Suppress hepatic glucose production
– Cover 50% of daily needs
• Bolus Insulin – short/ rapid acting insulins (Prandial)
– Immediate rise and sharp peak at 1 hr
– Limit postprandial hyperglycemia
– Cover 10-20% of total daily insulin requirement at each meal.
Basal/Bolus Treatment Regimen with Intermediate Acting and Regular Human Insulins
Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogues

METHODS OF INSULIN ADMINISTRATION
• Calculate the initial dose as Insulin 0.2-0.4 U/kg/day
• Adjust dose by ~ 4 U every 3-5 days
• Initial Regimen should be Simple
• Insulin therapy requires a structured program employing active insulin dose titration that
encompasses:
– injection technique, including rotating injection sites and avoiding repeated injections
at the same point within sites
– self-monitoring
– dose titration to target levels
– dietary understanding
– Management of hypoglycemia .
CASE STUDY 1
History
• M.T. is a 16 year old female from Adama town presented with increasing thirst, polyuria
and weight loss of 4 kgs over the past 3 weeks.
• She was treated for malaria 1month back
• Has no family history of DM
• Has no heat or cold intolerance
• No similar symptoms in the past
Physical exam
• Wt : 35 kg Ht: 156cm
• B/P 100/60mmHg PR= 96/min Temp=36.6 oC
• Dry tongue and buccal mucosa
• Lethargic
• Thyroid not palpable
• Liver is palpable 3cm BRCM, TVLS 12.5cm
• No other finding
Questions
– What are your differential diagnoses?
– What tests do you like to order to confirm your diagnosis?
Answer:
Laboratory test
• CBC-Normal
• Random Blood Sugar was 320mg/dl
• Urinalysis and Microscopy
 No protein,
 Ketone 2+ ,
 glucose 3+,
 negative microscopy

Questions
• Does she have diabetes?
– If so, which type? Discuss your reasons.
• Will you start her on treatment?
– If so, what drug will you start her with?
– At what dose?
– How frequently would you like to adjust her medicine?
• What else will you include in her management?
• What is the risk of chronic complication at time of diagnosis in this patient?
Answer:
Case Study Continued…

She was admitted and treated and improved and was discharged. She was appointed to come
after 1 week. 4 days later she was brought back by her relatives as they noticed that she was
talking irrelevant things and was very weak and was sweating profusely early in the morning.
Questions
• What could be the reason?
• What would you do?
• How would you like to treat?
• On follow up what will you do to avoid further episodes?
Answer:
HONEYMOON PERIOD
• After several weeks of exogenous insulin treatment & excellent metabolic control has been
established
• Dependency on exogenous insulin decreases or ceases entirely for weeks to months
• Temporary remission (honeymoon phase) is marked by an increase in serum C-peptide
levels which indicates an increase in endogenous insulin secretion
• Within 5 years after diagnosis of childhood type 1 diabetes mellitus, C-peptide virtually
disappears from the serum.

ROUTINE CARE RECOMMENDATIONS FOR PATIENTS WITH T1DM
A1C 2-4 times per year
Growth (Children
Height and weight 4 times per year
and adolescents)
Nutritionist At Diagnosis, then every year
Adult: at diagnosis, then every 1-2 years

Lipid profile Child (low-risk): every 1-5 years for age >10 years
Child (high-risk): every 1-5 years for age >2 years
Blood pressure Every Visit
Albumin/Creatinine ratio: annually once duration of diabetes >5 years

Nephropathy and age >10 years
Serum creatinine: every year (adults only)
ROUTINE CARE RECOMMENDED TARGETS FOR PATIENTS WITH T1DM
Parameter Treatment Goal for Non- Considerations for glycemic goals

pregnant Adults
A1C (%) • ≤7 % for most • Residual life expectancy

– Closer to normal for • Duration of DM
healthy • Presence or absence of micro- and
– Less stringent for macrovascular complications
“less healthy” • CVD risk factors
• Comorbid conditions
FPG (mg/dL) 80 - 130 • Risk for severe hypoglycemia
• Patient’s psychological, social, and
economic status
2-hour PPG <180
(mg/dL)

COMPLICATIONS OF INSULIN THERAPY
Some of the complications of insulin therapy include:
1. Hypoglycemia
• potentially life threatening
• Preventable
• Treatable
Carefully educate about recognition of hypoglycemic symptoms and Management
2. Weight Gain
Possible causes:
 Improvement in glycemic control
 Increased food intake to treat or prevent hypoglycemia .
 Insulin itself may stimulate appetite.
Management:
 Pre-inform patients
 Identify cause and try to correct
3. Worsening Retinopathy
 in severe background or proliferative retinopathy
 Regimens to achieve tight glucose control has been shown to exacerbate the underlying
retinopathy.
 treat the retinopathy before instituting tight glucose control.
4. Insulin Allergy
 less common with human insulin and insulin analogues
 Local reactions at the injection site.
 Can be to the insulin itself or other components such as the protamine in NPH
 generalized allergic reactions & anaphylactic shock are rare
Treatment of insulin allergy: mild local allergic reactions – antihistamines; severe reactions
require desensitization.
5. Dawn Phenomenon and Somogyi Phenomenon

There are several reasons that blood glucose levels increase in the early morning hours before
breakfast. The most common is a simple decline in insulin levels. This usually results in
routinely elevated morning glucose.
The dawn phenomenon is thought to be mainly caused by overnight growth hormone
secretion and increased insulin clearance. It is a normal physiologic process seen in most
adolescents without diabetes, who compensate with more insulin output. A child with T1DM
cannot compensate. The dawn phenomenon is usually recurrent and modestly elevates most
morning glucose levels.

Rarely, high morning glucose is caused by the Somogyi phenomenon, a theoretical rebound
from late-night or early-morning hypoglycemia, thought to be from an exaggerated counter-
regulatory response.
It is unlikely to be a common cause, in that most children remain hypoglycemic (do not
rebound) once nighttime glucose levels decline.
Check BG @ 2-3 am for a couple of days to clarify ambiguously elevated morning glucose levels.
6. Lipodystrophy (hypertrophy /atrophy)

 repeated single site injection
 easily accessible sites commonly affected
 forms lump at injection site
 less painful so patient tends to choose it for injection.
 insulin absorption from this site is not reliable.
PRACTICAL TIPS ABOUT INSULIN THERAPY

1. Insulin storage:
• Store insulin preferably @ 4-8 0c, in a fridge (do not freeze)
• in separate container
• not In a fridge door
• check expiry date
• if fridge not available, can be kept in a cool, dark, well ventilated place
Note: a vial in use is stable @ 25oc for 6 wks, @ 37oc for 4 wks
2. To mix cloudy insulin, roll between hands
3. Transporting insulin – advise pts to:
– carry adequate supply
– valid prescription
– carry insulin in a hand bag
– avoid keeping insulin in direct contact with ice pack
4. Mixing Insulins:
– inject air in to the vials before drawing insulin
– draw soluble insulin first, then the intermediate
– avoid contaminating short acting insulin with the intermediate acting one
– should be injected with in 5 minutes of mixing
– if there is difficulty mixing, better inject separately
5. Injection sites:
Abdomen, thighs, buttock, arms
• fast absorption from abdomen , slow from thigh

• preferred sites for soluble insulin - abdomen
• for longer acting insulin - the thighs
• caution! injecting on exercising muscle
• use one area for a particular time of the day
• rotate injection areas
• avoid injecting in to lipodystrophy site
Figure: Sites for Insulin Injection. Rate of absorption- abdomen> arm>leg and buttock
6. Injection techniques:
– no need of cleaning with alcohol
– if need be, clean with water
– make a skin fold - inject @ 90o in most with long needles or very thin pt.--@ 45o
– slight bleeding is ok
– never give intermidiate insulin IV
7. Before changing insulin dosages
Check
– insulin storage
– patient compliance
– injection techniques ( resuspension, dosages,
– mixing procedures, & injecting)
– injection sites

– eating plans, exercise, BG monitoring compliance
– other factors e.g. stress, infection, other illnesses
N. B. If food is not readily available, be cautious in dose escalation
UNIT 5 SUMMARY
Goals of treatment in type 1 DM include
 Decreasing plasma glucose levels and urine glucose excretion to eliminate symptoms
 Prevent diabetic ketoacidosis and severe hypoglycemia
 Inducing positive nitrogen balance to restore lean body mass and physical capability and
to maintain normal growth, development, and life functioning
 Preventing or greatly minimizing the late complications of diabetes
Management Components for Type 1 DM
 Patient and family education
 Setting targets
 Diet
 Exercise
 Reduction of risk factors
 Daily monitoring of blood glucose
 Use of Insulin – human and analogs

UNIT 6: MANAGEMENT OF TYPE II DIABETES: LIFE STYLE
INTERVENTIONS AND ORAL AGENTS
TOTAL TIME ALLOTTED TO UNIT 6: 2 hours and 30 minutes
OBJECTIVES OF THE UNIT
By the end of this unit, participants will be able to:

1. Describe the complex nature of type 2 diabetes & match pathophysiology to treatment
options
2. Describe life style interventions in the management of type 2 diabetes mellitus
3. List the various classes of oral agents for the treatment of type 2 DM with emphasis on
locally available ones
4. Describe mechanisms of action, side effects, efficacy & contraindications of oral
antidiabetic medications
5. Identify the importance of holistic & individualized approach in the management of type
2 DM
INTRODUCTION ABOUT TYPE II DM

Type 2 diabetes is associated with increased morbidity and mortality. This is mainly due to
cardiovascular complications. Intervention that are proven to decrease these burden are
comprehensive diabetes care with management of glycemia and other risks The two important
components of type 2 DM management are Life Style Modifications and medications.
Key Mechanisms of hyperglycemia in Type 2 DM includes:
o Insulin resistance
o β-cell failure due to glucotoxicity & lipotoxicity
o Increased endogenous glucose production
 Liver
 Kidney
Hyperglycemia has twin components
o Fasting hyperglycaemia
o Postprandial Hyperglycaemia.
Type 2 DM is a complex disease:
• Patients often fail to reach treatment goals
• There are associated disturbances:
– Over 45% are obese (BMI ≥30 kg/m2)
– As many as 75–80% have hypertension
– Over half of patients have hypercholesterolemia

– Atherothrombotic changes
• Effective management of Type 2 diabetes is beyond glycemic control
• Need to address BP, Lipids, Obesity and others
Important issues in Management of type 2 diabetes
• Patient education on the character of the disease
– Complex disease
– Progressive disease
– Lifetime treatment and follow up
• Motivating patients to make lifestyle adjustments
– Physical activity
– Healthy food intake
• Motivation of all HCP to persist with advice and motivation of patients
• Early and intensive intervention
– ↓Risk of microvascular and macrovascular complications
– ↓ Disease progression
– Comprehensive care improves outcome
BENEFITS OF INTENSIVE GLYCEMIC CONTROL AND TARGETS FOR CONTROL

(DCCT in Type1 DM & UKPDS in Type 2 DM & follow up studies)
Several researches have shown that intensive control of Glycemia in DM prevents or delays the
occurrence of micro-vascualr complications. Additionally the life style changes adopted to
control Glycemia also contribute positively to prevention of macrovascualr complications of
diabetes.
Studies also have shown that there is ‘Glycaemic metabolic memory’:
• Level of glucose control in the early years of disease impacts on the development of later
complications
• Patients with tighter glycaemic control during the study developed less micro- and
macrovascular complications more than 10 years after discontinuation of the study.
These observations emphasize the need to control glycaemia as tight as possible and as early in
the disease process as possible.
Based on those studies targets for glycemic control, BP and Lipids have been suggested.

Table: TARGETS FOR TYPE 2 DM MANAGEMENT: GLYCEMIA, LIPIDS AND BP
Parameter Target Recommendation

Preprandial capillary 80-130 mg/dl
plasma glucose (4.4–7.2 mmol/L)
Peak postprandial < 180 mg/dL

capillary plasma (10.0 mmol/L)
glucose
HbA1C (%) < 7.0% <6.5% if possible, 7-8% in
(53 mmol/mol) some cases
Blood Pressure <140/90 mmHg ACEIs or ARBs
2 or more drugs at
maximal doses are
needed
Administer one of the
drugs at bed time
Lipids Give Statins (Simvastatin, There are no specific
Atorvastatin, Rosuvastatin or targets for Total
Lovastatin) for the following group cholesterol or LDL or HDL
Diabetes Patients :
• DM + CVD
• Age > 40 yrs + 1 CVD risk factor
• Age < 40 yrs if LDL > 100 mg/dL
Atherothrombotic Give ASA 75-100mg PO for Primary

conditions prevention
• Males > 50 yrs, Females > 60 yrs +
1 CV risk factor
However the Glycemic Goals in Type 2 DM should be Patient-centered considering several

factors:
– Duration of diabetes
– Age/life expectancy
– Comorbid conditions
– Known CVD or advanced microvascular complications
– Hypoglycemia unawareness
– Individual patient considerations
Hence more or less stringent glycemic goals may be appropriate for individual patients.
• General Target < 7%
• More Stringent 6.0 % – 6.5 %

– Younger patients
– Newly diagnosed
– Long-standing disease, no significant complications
• Less Stringent 7.5% - 8.0%
– Older patients
– Long-standing disease & significant complications
– CV risk factors
– History of CVD
As shown in the diagram below characteristics/predicaments towards the left justify more
stringent efforts to lower HbA1c, whereas those towards the right are compatible with less
stringent efforts. Where possible, such decisions should be made in conjunction with the
patient, reflecting his or her preferences, needs and values.
CASE STUDY 1
Mr. F.A is a 42 years old male patient presented for routine checkup. His physical exam is non
remarkable except for BMI of 24 kg/m2. You found out that his FBS is 129 mg/dl and 132 mg/dl
on two different occasions. What is the best initial treatment for this patient?
A. Metformin 500 mg BID
B. Glibenclamide 2.5 mg/d
C. Start NPH insulin
D. Advice on life style intervention
Answer:

COMPREHENSIVE DIABETES CARE
Principles of Care
1. Lifestyle modifications
2. Individualized approach
3. Address both FPG & PPG
4. Minimize risk of hypo & weight gain
5. Major cost comes from complications and not from medications
6. Combination therapy usually required
7. Comprehensive BP and Lipid Management
8. Initial regimen should be simple
Optimal diabetic therapy involves beyond glycemic control

• Diagnosis & Management of DM specific complications
• Modify risk factors and associated conditions
• Social, family, financial, employment & cultural issues
• Diabetes education
• Medical nutritional therapy
• Exercise
Lifestyle Modifications involves:

• Healthy Diet
• Regular Exercise
• Ideal Weight
• No Smoking
• Avoidance of Alcohol Abuse
RECOMMENDED SCHEDULES FOR ONGOING MEDICAL CARE OF DIABETES
 Self Monitoring of Blood Glucose (≥3/day, individualize)
 A1C (2-4x/yr)
 DM Management patient education (annual)
 Medical Nutritional Therpy (annual)
 Eye exam (at Diagnosis for type 2 DM, annual or Q2-3yrs)
 Foot exam (by patients daily, by doctor 1-2x/yr)
 Microalbuminuria (annual)
 BP measurement (Quarterly)
 Lipid profile (annual)
 Others: immunization, antiplatelets

In the subsequent paragraphs the details of these comprehensive diabetes care package is
discussed.
1. DIABETES SELF MANAGEMENT EDUCATION
– Incorporates knowledge and skills development, as well as cognitive behavioral
interventions
– Should be implemented for all individuals with diabetes.
– Fundamental component of diabetes care
– Most effective when ongoing diabetes education and comprehensive healthcare occur
together
– Usually multidisciplinary i.e. educator, dietitian & doctor work together
– Often group based
– The content must be individualized according to the individual’s type of diabetes, current
state of metabolic stability, treatment recommendations, readiness for change, learning
style, ability, resources and motivation.
DIABETES EDUCATION IS A CORNER STONE FOR DIABETES CARE
 Diabetes Self Management Education (DSME)
 optimizes metabolic control and helps to Prevent and manage complications
 Maximizes quality of life, in cost effective manner
 should address psychosocial issues, since emotional well-being is strongly associated
with positive diabetes outcomes
 It leads to improved diabetes knowledge and self-care behavior
 Improves clinical outcomes (lower HBA1C , high self reported weight loss , and
improved quality of life .)
 It should be continuous and must include a follow-up support
DSME SHOULD INCLUDE
 optimal and appropriate use of therapy to address:
– basic knowledge of diabetes
– Nutrition and physical activity
– SMBG and A1C and the targets of control
– Acute complications of therapy
– Intercurrent illness
– Knowledge of late complications
– Psychological aspects of living with diabetes
– Dealing with lifestyle and life event
– Foot & skin care
– Diabetes management before, during, and after exercise

– Risk factor–modifying activities.
2. PHYSICAL EXERCISE
• Multiple positive benefits that includes:
 Lowering plasma glucose (during
and following exercise)
 Improves insulin sensitivity
 Improves lipid profile
 Helps to control BP
 Improves CV function
 Diminishes potential for weight
gain
 Increases sense of well-being
 Increases flexibility and muscle
strength
Types of Exercise
a) Aerobic exercise
 Includes endurance exercise
 Walking, riding bikes, swimming
 Improves cardiac fitness
b) Anaerobic exercise
 Lasts for short durations
 Resistance training (lifting weights)
 Flexibility training (stretching)
 Improves muscle strength
Recommendations on exercise:
– Exercise daily for 30 minutes (min 5 days/wk)
– Intensity should be individualized
– Watch out for hypoglycemia for patients on insulin and sulfonylureas.
3. PSYCHOSOCIAL ASSESSMENT AND CARE

• Ongoing part of medical management of diabetes
• Psychosocial screening and follow-up may include, but are not limited to, attitudes
about the illness, expectations for medical management and outcomes, affect/mood,
general and diabetes-related quality of life, resources (financial, social, and emotional),
and psychiatric history

• Routinely screen for psychosocial problems: depression, diabetes-related distress,
anxiety, eating disorders, cognitive impairment.
• Emotional well-being is an important part of diabetes care and self-management
4. MEDICAL NUTRITION THERAPY (MNT)
It is the term used by the American Diabetic Association to describe the optimal coordination of
caloric intake with other aspects of diabetes therapy (OHA, insulin, exercise, weight reduction).
STEPS TOWARDS THE FIRS ACTION:
a) Determine : Past dietary history; physical activity; socioeconomic status; cultural &
religious practice.
b) Weight Assessment:
• Broca’s Index: Height in cm - 100 = desirable weight in kg
• Body Mass Index: Weight (in kg) / (Height (in m)) 2
c) Assessment of caloric requirement
• Daily caloric requirement depend the patient weight, age, activity
• Total energy requirement (TER) = Basal Metabolic rate (BMR) + Activity factor
– BMR for males = 24 kcal / kg / day
– BMR for females = 22 kcal/kg/day
• Assess Activity Factor:
– Sedentary level: 25-30% BMR
– Moderate activity: 35-50% BMR
– Strenuous activity: 50-100% BMR
DIETARY ADVICE AND CALORIC DISTRIBUTION
o Food must be spread evenly throughout the waking hours, and taken at regular times in
relation to the insulin dose.
o The diet must be balanced in relation to CHO, FATS, and PROTIENS
o Avoid rapidly absorbed CHO, must be nutritious & adequate amount.
Fig: Percent Nutrients Changed to Blood Glucose

o Approximately the same amount of food should be eaten every day
o Diet should be based on the ordinary foods used by the family

NUTRITIONAL RECOMMENDATIONS FOR ADULTS WITH DIABETES
• Carbohydrate
– 45–65% of total caloric intake (low-carbohydrate diets are not recommended)
– Amount and type of carbohydrate important
– Sucrose-containing foods may be consumed with adjustments in insulin dose
• Protein
– 10–35% of total caloric intake (high-protein diets are not recommended)
• Fat
– 35% of total caloric intake
– Saturated fat < 7% of total calories
– <200 mg/day of dietary cholesterol
– Two or more servings of fish per week provide 3 polyunsaturated fatty acid
– Minimal trans fat consumption
• Other components
– Fiber-containing foods may reduce postprandial glucose excursions
– Non-nutrient sweeteners.
5. PRINCIPLES ON THE USE OF ORAL GLUCOSE LOWERING MEDICATIONS

• Used to Meet Glycemic Targets
• Should not be delayed
• Monotherapy or Combination Therapy
• Address Both Fasting & Postprandial Hyperglycemias
• Stepped-Care Approach is Recommended
• Initial Therapy is with Metformin
• When Combination Therapy Fails use Insulin as soon as possible
• Watch for Side Effects.
CASE STUDY 1 CONTINUED

The same patient came back to you on follow up after three months and his FBS is in the range
of 170-200 mg/dl. You make a diagnosis of poor glycemic control. The best next step in this
patient’s glycemic management is:
A. Intensify Life Style Changes
B. Metformin 500 mg/d
C. Glibenclamide 5 mg/d
D. Vildagliptin 50 mg BID
E. Start insulin
Answer:

MAIN SITES OF ACTION FOR ANTIDIABETES AGENTS
Different antidiabetes drugs target distinct sites as part of their primary mechanism for
reducing hyperglycemia as shown in the figure below:
Figure: Different anti-diabetes drugs target distinct sites as part of their primary mechanism for
reducing hyperglycemia as shown.
A) Traditional Oral Agents
1. Sulfonylureas – stimulate insulin secretion
 Glibenclamide ,Glipizide, Glimepiride, Gliclazide
2. Meglitinides – stimulate insulin secretion
 Repaglinide, Nateglinide
3. Alpha Glucosidase inhibitors – delay Carbohydrate absorption
 Acarbose, Miglitol
4. Biguanides – reduce hepatic glucose production
 Metformin
5. Thiazolodinediones- improve insulin sensitivity
 Rosiglitazone, Pioglitazone
B) Newer Hypoglycemic Agents
6. GLP 1 Receptor Antagonists-increase insulin secretion through incretin effect of food
– Exenatide (injectable)
7. DPP4 inhibitors –inhibit clearance of GLP1 by the enzyme DPP4: gliptins
– Alogliptin, Saxagliptin, Sitagliptin, Vildagliptin
8. SGLT2 Inhibitors – promote urinary excretion of glucose
– Canagliflozin, Dapagliflozin, Empagliflozin

Table: Comparison of Glucose Lowering Agents
STEPPED-CARE APPROACH IN MANAGEMENT OF TYPE 2DM

Lifestyle modification by itself can only provide control of blood glucose concentrations to
target levels in a minority of people with diabetes, and then usually only for a limited period
after diagnosis. Accordingly, supplementary pharmaceutical measures are needed, and these
can be oral glucose lowering medications, GLP-1 Receptor Antagonists or insulin injection
therapy, separately or in combination.
The natural history of type 2 diabetes is of progression of islet β-cell failure. Ultimately insulin
remains the only glucose-lowering therapy which can maintain blood glucose control despite
such progression.
CHOICE OF INITIAL GLUCOSE-LOWERING AGENT

 Patients with FPG < 180mg/dl---Life style changes for maximum 2-3 months
 Patients with FPG 180-250 mg/dL - single OHA
 Patients with FPG > 250 mg/dL – combination OHAs
 Insulin can be used as initial therapy in individuals with severe hyperglycemia FPG >
250–300 mg/dL or in those who are symptomatic from the hyperglycemia.
– To reduce “glucose toxicity” to the islet cells

Figure: Antihyperglycemic therapy in type 2 diabetes: general recommendations.
Potential sequences of antihyperglycemic therapy for patients with type 2diabetes are
displayed, with the usual transition moving vertically from top to bottom.
DPP-4-i, DPP-4 inhibitor; fxs, fractures; GI, gastrointestinal;GLP-1-RA, GLP-1 receptor
agonist; GU, genitourinary; HF, heart failure; Hypo, hypoglycemia; SGLT2-i, SGLT2
inhibitor; SU, sulfonylurea;TZD, thiazolidinedione.

ORALHYPOGLYCEMIC AGENTS IN USE
Drug Duration (hours) Dose (mg) Frequency
Sulfonylureas
Glibenclamide 12 - 24 2.5-20 1-2x
Glipizide 12-18 2.5–40 1-2x
Glimepiride 24 1-8 Once
Meglitinides
Repaglinide 2-6 0.5-16 3x
Nateglinide 2-4 180-360 3x
α-glucosidase Inhibitors
Acarbose 3-4 150-300 3x
Miglitol 12-18 150-300 3x
Biguanide
Metformin 0.5-2g 3x
Thiazolidinediones
Pioglitazone 2-4 15-45 Once
SGLT2 Inhibitors
Dapagliflozin 10 Once
Canagliflozin 100mg, Once
300mg
Combinations: MTF+ Glibenclamide, pioglitazone +MTF, sitagliptin +MTF, vildagliptin
+ MTF, saxagliptin +MTF
a) METFORMIN:
Mechanism of Action
• Decrease hepatic glucose production (gluconeogenesis, glycogenolysis) *

• Increase insulin-mediated muscle glucose uptake
• Decrease gastrointestinal glucose absorption
• Inhibition of adipose tissue lipolysis (FFA)
Efficacy
• Glucose effects:
– Decreases A1c by 1.5-2%
– Decreases fasting glucose by 50-70 mg/dl
• Effects on Complications and disease progression:

– Often promotes slight weight loss
– improves the lipid profile
– Proven to decrease microvascular complications of diabetes (UKPDS Trial)
– Shown to decrease progression from “pre-diabetes” to overt diabetes (DPP Trial)
Metformin: Side effects and Contra-indications
Side Effects Contraindications
• GI Intolerance (dose-dependent) • Severe Renal Insufficiency (ESRD)
• Nausea, • Severe CHF
• Diarrhea – Renal hypoperfusion
• Metallic taste • Chronic Liver Disease
• Lactic Acidosis – Includes EtOH
– 1 in 40,000 patients • Chronic lung disease
• Risk Factor: Renal Insufficiency • IV Contrast Studies
(decreased clearance of lactate) – Renal Effect
• No Hypoglycemia (when used as – Restart in 48 hours
monotherapy) • Major Surgery
– No effect on pancreatic insulin • Severe Acute Illness
secretion
• Vitamin B12 deficiency
Because of its relatively slow onset of action and gastrointestinal symptoms with higher doses,
the initial dose should be low and then escalated every 2–3 weeks based on SMBG
measurements.
Metformin is effective as monotherapy and can be used in combination with other oral agents or
with insulin.
There are new recommendations on use of insulin in patients with renal insufficiency as shown
in the table below. With the new recommendation use of Metformin is restricted only for
patients with end stage renal disease

b) SULPHONYLUREAS
• Stimulate Insulin Secretion
• Their Action Requires Functioning Beta Cells
• Side Effects
– Hypoglycemia
– Weight Gain
– GI Upset, Allergy
• Contraindications
– Allergy to the drug
– Type 1 DM
– Early Pregnancy
– Severe Infections
– Hepatic/Renal Failure
– Surgery
c) INCRETINS (Glucagon-Like Peptide –1)(GLP-1)

• Release is Rapid in Response to Meals
o Potent Insulinotropic Hormone
o Decreases Glucagon Release
o Slows Gastric Emptying
o Reduces Food Intake
• Rejuvenate β Cells (in animals)
• There is lower Plasma GLP-1 in IGT & Type 2 DM.
• GLP-1 Agonists - ↑ Insulin, ↓ glucagon, slow gastric emptying, satiety
 e.g. Exenatide, liraglutide, Dulaglutide
 Unfortunately they are given parenterally
d) DPP4 Inhibitors: Inhibit GLP-1 Breakdown
• Sitagliptin
• Saxagliptin
• Vildagliptin
• Linagliptin
• Alogliptin
• Combinations with Metformin
• THESE DRUGS SHOULD BE PRESCRIBED BY PHYSICIANS INTERNISTS/
ENDOCRINOLOGISTS

WHY ARE WE NOT MEETING TARGETS?
The reasons for not meeting targets may be many but the most important ones are the
following:
• Reluctance by Patients and Professionals
• Not treating to targets
• Not addressing Postprandial Hyperglycemia
• Fear of Hypo
• Late Introduction of Insulin
• Current Drugs – not effective
As patients HbA1C approaches the target the contribution of postprandial hyperglycemia is

higher. So add agents that can address this condition.
Remember that diabetes is a Polypharmacy Condition

• Glucose Control requires 2-3 Drugs
• Cholesterol Control may need 1-2 Drugs
• Blood Pressure Control requires at least 2 Drugs
• Neuropathy Drugs
• Aspirin
• Nondiabetes Medications
Hence good adherence counseling and close follow up is needed.

Follow up of DM should look like the following
UNIT 6 SUMMARY
• Diabetes care should be comprehensive, not only glucocenteric
• Lifestyle interventions: DSME, diet, and exercise with other risk reductions are equally
important in optimizing diabetes care
• Different classes of oral antidiabetic medications are available
• Metformin is the first line therapy unless there is contraindication
• Patient’s glycemic level guides in initiation of single or dual therapy
• Individualization is crucial in heading towards the therapeutic goals, one size does not
fit all

UNIT 7: INSULIN INITIATION AND TITRATION IN TYPE 2 DIABETES
TOTAL TIME ALLOTTED TO UNIT 6: 1 hour and 30 minutes

LEARNING OBJECTIVES
At the end of this UNIT participants will be able to:

• Describe the approaches in management of Type 2 diabetes
• List the rationale and indications for insulin initiation in Type 2 DM
• Choose the right insulin type and dose
• Educate the patient and family members on proper injection of insulin
• Address barriers to optimal use of insulin
• Support patients on insulin therapy
INTRODUCTION
Type 2 diabetes is a progressive disease marked by increasing insulin resistance and failure of
the pancreatic beta cells to produce insulin.
Getting to, or maintaining, target HbA1c levels in T2DM requires intensified treatment over time.
Combination therapy of OADs can fail eventually, not just OAD monotherapy as the
graph below shows the result of follow up of 2220 patients with T2DM treated with MET + SU.
Hence a stepped care approach should be followed

REASONS TO START INSULIN IN TYPE 2 DM
• HBA1c >9.5% (or FPG>250mg/dl or RBS>300mg/dl) with symptoms at diagnosis
• Lean individuals or those with severe weight loss
• A1c >7% (or FBG >130)despite oral meds and Life Style Modification
• Intolerable side effects to oral agents
• unable to take medications due to kidney, liver, heart, or allergy issues
• Preparation for conception and Pregnancy
• Plans for surgery, especially CV surgery
• Severe illness or Hospitalization
• Use of steroids or chemotherapy
OPTIONS FOR INSULIN THERAPY IN TYPE 2 DM

• Offer NPH insulin injected as once or twice daily according to need.
• Consider starting both NPH and short-acting insulin if person’s HbA1c is 9.0% or higher,
administered either:
– separately or
– as a pre-mixed (biphasic) human insulin preparation.
 Insulin therapy options
– Basal insulin- Once or twice daily, intermediate or long-acting
– Premix insulin- Once or twice daily
– Rapid-acting insulin (bolus)- Meal-time
– Combination (e.g. basal-bolus)
INITIATING BASAL INSULIN THERAPY
OAD, oral antidiabetic agent; TDD, total daily dose.

a Continue OADs unless specific contraindications.

INSULIN INITIATION REGIMENS
• Basal insulin
– 10 units at bed time
– Increase by 2 unit every 3 days until fasting glucose < 130 mg/dl
• Intensive insulin therapy/Multiple Daily Injections(MDI)
– 0.3-0.5 units/kg total
• Divide dose 2/3 in AM + 1/3 in PM
– Increase by 2 unit every 3 days until fasting glucose < 130 mg/dl
• Pre-mixed insulin
– 10 units bid OR 0.3-0.5 units/kg divided in 2/3 in AM + 1/3 in PM
– Most difficult to titrate
PRACTICAL ASPECTS OF INSULIN INITIATION

• Start low and titrate up
• Basal insulin therapy:
– Begin at 0.1 to 0.2 U/kg of body weight = ~ 10 units at bed time and titrate to achieve
target fasting, if the bed time insulin is ≥24 units, split 2/3 in AM + 1/3 in PM
– Continue metformin therapy
– Continue sulfonylureas during the day if started with bed time NPH
• If patients have post prandial high blood glucose (>180 mg/dl):
– Continue Metformin and DPP-IV inhibitors
– Stop sulfonylureas
– Calculate 0.3 to 0.5 u of insulin/kg body weight
– Premixed insulin twice daily: divide as 2/3 in AM and 1/3 at supper and titrate
– Patients can also mix NPH insulin and regular insulin in 2/3 and 1/3 proportions
respectively
– Have patients work closely with diabetes nurse educator or frequent follow ups in the
office for adjustment.
• Insulin therapy requires a structured program employing active insulin dose titration
that encompasses:
– injection technique, including rotating injection sites and avoiding repeated injections
at the same point within sites
– self-monitoring
– dose titration to target levels
– dietary understanding
– management of hypoglycaemia

BARRIERS TO INSULIN THERAPY
• There is resistance to initiate insulin despite efficacy and guideline recommendations
(‘clinical inertia’)
– Patients remain on OAD therapy for years, even those with poor glycaemic control
• Barriers to insulin initiation are shared by patients and physicians
• Patient concerns continue even after insulin initiation
Patients and family Health Care workers

• Fear of hypoglycaemia • Lack of
• Fear of reduced quality of life – Training
• Fear of needles/pain from injections – Time
• Reluctance to inject in public – Support & Resources
• Perception that the disease is • Do not treat to target
becoming more severe • Fear of
• Patients do not feel empowered to take – Hypoglycemia
control of their diabetes – Weight gain
• Perception that insulin therapy leads – Patients’ anger
to complications or death – Complex RX regimens
• Misperception that insulin is only
necessary in type 1 diabetes
COMMON REASONS FOR CLINICAL INERTIA
Figure: Possible barriers to initiating Insulin Therapy by patients and clinicians

Figure: Patient concerns continue even after starting insulin calling for need of continued
patient support.
Proper and repeated explanation about the benefits, uses and potential risks and how to avoid
them should be done for patients and; clinicians should be trained on the proper use of insulin
in diabetes.
DETERMINANTS OF INSULIN EFFICACY
Efficacy of insulin therapy is affected by several factors:
• Type of insulin
• Size of subcutaneous tissue
• Injection technique
• Site of injection
• Alterations in subcutaneous blood flow
• Inadequate mixing of NPH insulin
• Adherence of the patient to prescribed regimen and diet and exercise program.
INSULIN INJECTION TECHNIQUE

Injection technique is the same with insulin syringes and pen injectors. Both the angle of needle
entry and depth of penetration affect the rate of absorption.
Injections are made into the subcutaneous tissue. Most individuals are able to lightly grasp a
fold of skin and inject at a 90° angle. Thin individuals or children can use short needles or may
need to pinch the skin and inject at a 45° angle to avoid intramuscular injection, especially in the
thigh area.
INJECTION SITES
• Insulin may be injected into the subcutaneous tissue of the upper arm and the anterior and
lateral aspects of the thigh, buttocks, and the abdomen.

• The most common injection site is the abdomen. The back of the upper arms, the upper
buttocks or hips, and the outer side of the thighs are also used. These sites are the best to
inject into for two reasons:
– They have a layer of fat just below the skin to absorb the insulin, but not many nerves
which means that injecting there will be more comfortable than injecting in other parts
of your body.
– They make it easier to inject into the subcutaneous tissue, where insulin injection is
recommended.
• Rotation of the injection site is important to prevent lipohypertrophy or lipoatrophy.
• Rotating within one area is recommended (e.g., rotating injections systematically within the
abdomen) rather than rotating to a different area with each injection.
• The rate of absorption varies among the sites:

– Fastest from the abdomen (stomach)
– A little slower from the arms
– Even slower from the legs
– Slowest from the buttocks
INSULIN STORAGE
• Although manufacturers recommend storing insulin in the refrigerator, injecting cold
insulin can sometimes make the injection more painful.
• To avoid this, many providers suggest storing the bottle of insulin being used at room
temperature .
• Insulin kept at room temperature will last approximately 1 month

CASE STUDY ONE
A 42 year old man with diabetes for the last 03 years is taking Metformin 1000mg PO bid and
Glibenclamide 5mg PO bid.
His FBS is 210 mg/dl today. His HbAlc is 9%. His FBS was 300mg/dl at diagnosis but refused to
insulin initiation because of fear of hypoglycemia and interference with his daily routine.
He has background retinopathy and dyslipidemia.
He has determined his blood sugar for the last one week and the average is:
FBS (mg/dl) Pre dinner (mg/dl) 2hr post meal (mg/dl)
220 205 250
QUESTIONS
• How would you manage this patient?
• How would you address his concerns regarding use of insulin?
ANSWER:
UNIT 7SUMMARY
• Diabetes is a progressive disease
• T2DM progression is characterised by decline in ß-cell function and worsening insulin
resistance.
• Getting to, or maintaining, target HbA1c levels in T2DM requires intensified treatment over
time.

UNIT 8: DIABETES IN CHILDREN AND ADOLESCENTS
TOTAL TIME ALLOTTED TO UNIT 6: 3 hour and 30 minutes
LEARNING OBJECTIVE
At the end of this UNIT the participants will be able to
 Define and diagnosis DM in children
 Describe epidemiology, pathogenesis and clinical features of Type 1 DM in children
 List the comprehensive management of Type 1 DM in children
 Describe the treatment goals and monitoring frame work of type 1 DM
 Explain acute complication of Type 1 DM and manage the complications
 Diagnose and treat Hypoglycemia
 Discuss the chronic complications of type 1 DM in children
 Discuss the screening and management of the emerging Type 2 DM in children
A. INTRODUCTION TO DIABETES IN CHILDREN AND ADOLESCENTS

Diabetes is one of the most common diseases in school-aged children. Both type 1 and
type 2 diabetes are increasing in children and adolescents.
– Type 1 diabetes accounts for over 90% of childhood and adolescent diabetes.
– Type 2 diabetes is becoming more common in adolescents, particularly in the
peripubertal period, and accounts for a significant proportion of youth onset
diabetes in certain at risk populations.
B. TYPE 1 DM IN CHILDREN AND ADOLESCENTS

INTRODUCTION:
Type 1 diabetes mellitus (T1DM), one of the most common chronic diseases in
childhood, is caused by insulin deficiency following destruction of the insulin-producing
pancreatic beta cells. It most commonly presents in childhood, but one-fourth of cases
are diagnosed in adults.
T1DM remains the most common form of diabetes in childhood despite the increasing
rate of type 2 diabetes. Type 1 diabetes is increasing by 3-5% per year.
EPIDEMIOLOGY
The incidence of childhood type 1 diabetes (T1DM) varies based upon geography, age,
gender, family history, and ethnicity.
Geographical variation: The incidence of childhood T1DM varies worldwide,
ranging from 0.1 to 65 per 100,000 children younger than the age of 15 years.
Age and gender - The age of presentation of childhood onset T1DM has a
bimodal distribution, with one peak at 4 to 6 years of age and a second in early

puberty (10 to 14 years of age. There appears to be no overall gender difference
in the incidence of childhood T1DM.
Risk Factors - Both genetic and environmental factors contribute to the risk of
developing type 1 diabetes mellitus (T1DM).
– Genetic susceptibility — The lifetime risk of developing T1DM is
significantly increased in close relatives of a patient with T1DM.
– Other risk factors — In genetically susceptible individuals, exposure to one
or more environmental agents appears to trigger an immune response that
ultimately causes destruction of the insulin-producing pancreatic beta cells.
PATHOGENESIS AND PATHOPHYSIOLOGY

In type 1 diabetes the body is unable to fully use glucose, and starts to break down fat
and muscle, resulting in weight loss. The kidneys are unable to reabsorb all the filtered
glucose. The glucose is excreted in the urine (glucosuria), dragging water with it
resulting in polyuria (excessive urination) and polydipsia (excessive drinking) due to
enhanced thirst because of increased serum osmolality from hyperglycemia and
hypovolemia.
– Younger children often resume bedwetting or daytime incontinence may occur
in a previously continent child.
– In children who are not toilet trained, parents may note an increased frequency
of wet diapers and/or diapers that are unusually heavy (wet).
Insulin deficiency in diabetic children impairs glucose utilization in skeletal muscle and
increases fat and muscle breakdown. Initially, appetite is increased, but over time,
children are more thirsty than hungry, and ketosis leads to nausea and anorexia,
contributing to weight loss.
Breakdown of fat causes ketones to accumulate in the blood (acidosis). If diagnosis is

not made, glucose and ketone levels become very high, resulting in severe dehydration
and loss of electrolytes from the body. This is called diabetic ketoacidosis (DKA).
The presence of ketones and the accompanying acidosis may cause an acetone/sweet
smell on the breath, vomiting, abdominal pain, decreased level of consciousness and
rapid deep breathing called Kussmaul respiration. If untreated, shock, cerebral oedema,
coma ensue and death may occur.
CLINICAL PRESENTATION
Childhood type 1 diabetes mellitus (T1DM) can present in several different ways:
a) Classic new onset of chronic polydipsia, polyuria, and weight loss with
hyperglycemia and ketonemia (or ketonuria)
b) Diabetic ketoacidosis
c) Silent (asymptomatic) incidental discovery

As shown in the table below the clinical manifestations differ.
a) DIABETIC KETOACIDOSIS
Diabetic ketoacidosis (hyperglycemia and ketoacidosis) is the second most common
form of presentation for T1DM in most populations.
Symptoms are similar but usually more severe than those of patients without acidosis.
In addition to polyuria, polydipsia, and weight loss, patients with ketoacidosis may
present with a fruity-smelling breath and neurologic findings including drowsiness and
lethargy.
DKA can be misinterpreted as an acute vomiting illness because classic pediatric
symptoms of dehydration (decreased urination) are masked by the polyuria that is
associated with glucosuria.
The reported frequency of diabetic ketoacidosis (DKA) as the initial presentation for
childhood T1DM is approximately 30 percent.
Young children (<six years of age) or those from an adverse socioeconomic background
are more likely to have DKA as their initial presentation of T1DM.
Among children younger than age three years, more than half had DKA as their initial
presentation of T1DM.
Children with DKA require hospitalization, rehydration, and insulin replacement
therapy.
b) SILENT PRESENTATION
Some children will be diagnosed with T1DM before the onset of clinical symptoms. This
presentation is least common and typically occurs in children who have another close
family member with T1DM and are being closely monitored. The diagnosis often is
made by either a family member or clinician with a high index of suspicion.
In babies and young infants, signs and symptoms of diabetes may be less easily
detected.

Diabetes in children is often misdiagnosed as some other condition – e.g.
– as pneumonia or asthma (labored breathing),
– as appendicitis or gastroenteritis (abdominal pain, vomiting),
– as a serious infection such as malaria, typhoid, HIV, tuberculosis, or meningitis
(coma etc.),
– as a urinary tract infection (urinary frequency), or
– as malnutrition (weight loss, tiredness)
Hence a high index of suspicion is required for diagnosis of DM especially in preschool
children.
The history or presence of prolonged or recurrent candidal infection (usually in the
diaper area) is an important clue that should raise suspicion about the possibility of
diabetes mellitus in young children.
DIAGNOSIS OF TYPE 1 DIABETES MELLITUS IN CHILDREN AND ADOLESCENTS

Diabetes mellitus is diagnosed based upon one of the following four signs of abnormal
glucose metabolism (and is similar to adults)
 Fasting plasma glucose ≥126 mg/dL (7mmol/L) on more than one occasion.
Fasting is defined as no caloric intake for at least eight hours.
 Random venous plasma glucose ≥200 mg/dL (11.1 mmol/L) in a patient with
classic symptoms of hyperglycemia
 Plasma glucose ≥200 mg/dL (11.1 mmol/L) measured two hours after a glucose
load of 1.75 g/kg (maximum dose of 75 g) in an oral glucose tolerance test (OGTT).
OGTT is seldom necessary to diagnose T1DM.
 Glycated hemoglobin (A1C) ≥6.5 percent . This criterion is more useful to diagnosis
of type 2 diabetes mellitus (T2DM) in adults, and should be confirmed by
hyperglycemia.
Unless unequivocal symptomatic hyperglycemia is present, the diagnosis should be
confirmed by repeat testing
Glucosuria is suggestive of diabetes, but not is diagnostic.
TYPE 1 VERSUS TYPE 2 DIABETES IN CHILDREN AND ADOLESCENTS

T1DM is characterized primarily by insulin deficiency, whereas type 2 diabetes (T2DM)
is characterized primarily by insulin resistance with relative insulin deficiency.
No set of criteria or diagnostic test can consistently distinguish between T1DM and
T2DM. Therefore, differentiating between the two types is based upon a combination of
the clinical presentation and history, often supported by laboratory studies.
Refer to the table below which shows comparison of Type 1 and Type DM.

Table: Clinical characteristics of type 1 diabetes and type 2 diabetes in children and
adolescents
NB: Obese is defined in children as body mass index [BMI] ≥95th percentile for age
and gender)
Some patients may have mixed features both Type 1 and Type 2 DM, and are difficult to
classify.
MANAGEMENT OF TYPE 1 DM IN CHILDREN AND ADOLESCENTS
There are unique challenges in caring for children and adolescents with diabetes that
differentiate pediatric from adult care.
These include the obvious differences in the size of the patients, developmental issues
such as the unpredictability of a toddler's dietary intake and activity level and inability
to communicate symptoms of hypoglycemia, and medical issues such as the increased
risk of hypoglycemia and diabetic ketoacidosis (DKA). Because of these considerations,
the management of a child with type 1 diabetes must take into account the age and
developmental maturity of the child.
Successful management of children with diabetes includes the following:

 Balancing the goal of strict glycemic control, which reduces the risk of long-
term sequelae of chronic hyperglycemia, against the goal of avoiding severe
hypoglycemia, which is more likely with stricter control.

o Targeted glycemic goals define what is thought to be the best balance
between these long- and short-term complications.
 Setting realistic goals for each child and family. The patient's age and
developmental status, and the level of family involvement are important factors
in establishing a practical management plan that can be implemented by the
patient and family.
 Training the patient and family to provide appropriate daily diabetes care in
order to attain glucose control within the range of predetermined goals, and to
recognize and treat hypoglycemia.
 Maintaining normal growth, development, and emotional maturation, with
increasing independence and self-care of diabetes as the child grows older.
CASE STUDY ONE
The mother of a six-year old child came to pediatric OPD with concerns about her daughter's
one-day history of abdominal discomfort.
The girl had managed to spend the day in school but her condition seemed to have worsened
since coming home and had been vomiting twice. There was no apparent fever, diarrhea, rash,
pain elsewhere, photophobia or altered behavior, or dysuria, and some simple painkillers had
made very little difference.
No other family member was currently unwell with any gastrointestinal conditions and no
obvious unusual food intake in the last three days.
There was little medical history - the child was born at term, developed well, was vaccinated for
her age, had had chickenpox and a few reviews for minor illnesses. She had a mild head injury six
months before, with no further consequences. There was no current medication or allergy
history.
The child vomited once more during this time but on evaluation by the clinician she looked well,
smiled and did not appear clinically dehydrated or in distress. She was apyrexial, the abdomen
felt soft and did not reveal any specific tenderness, guarding or rebound, and the bowel sounds
were normal.
The clinician reassured the mother and gave her daughter albendazole for possible intestinal
parasitosis.
As they were leaving the exam room the daughter asked her mother for water, and the mother
mentioned to the clinician that her daughter was unusually thirsty the past few days.
1. What is the differential diagnosis for this child’s problem?
2. What additional information do you like to know?
3. What additional tests do you like to do?
Answer:

Case Study 1 Additional information
She has started bed wetting at night for the past 3 days which the mother didn’t know. Two
weeks ago the child was 20kgs.
Her current weight is 18 kg
Height is 110cm
RBS:300mg/dl
Urine ketone: +
Stool exam:-ve
Urine Microscopy was WBC2-3/HPF
Question:
How will you manage this patient?
Answer:
COMPONENTS OF ROUTINE CARE OF TYPE 1DIABETES IN CHILDREN &

ADOLESCENTS
9. Diabetic education
10. Dietary Advice & growth monitoring using growth charts
11. Physical activity
12. Insulin Therapy
13. Monitoring Glycemic Control: Home blood glucose testing & Use of HbA1c to monitor the
glycemic control
14. Psychosocial issues assessment and management
15. Hypoglycemia management,
i. DIABETES EDUCATION
Training and care of the patient and family is divided into two management phases
In the initial phase, treatment with insulin is initiated, and the patient and family are
taught the most essential skills to safely manage diabetes.
In the second phase, the family is given further education and support to optimize
glycemic control and long-term management.
a) DIABETES EDUCATION: INITIAL MANAGEMENT

The initial phase begins at the time of diagnosis. In these first few days, the family
begins to understand the disease process and is trained to successfully measure blood
glucose concentrations, administer insulin, recognize and treat hypoglycemia, and check
blood or urine ketone concentration
 Basic understanding – The diabetes team teaches the patient and family the cause
and treatment of type 1 diabetes, how to maintain a daily schedule and record of

blood glucose test results, insulin administration, and the timing and carbohydrate
content of meals and snacks.
 Blood glucose testing – Families must master blood glucose testing. The parents
or caregivers are instructed on the frequency and timing of blood glucose testing,
depending upon the needs of their child.
 Insulin administration – Training includes teaching the family about the different
types of prescribed insulin, how to measure and inject insulin, and how to rotate
injection sites. Family members and caretakers must learn about the duration and
action of the various types of insulin prescribed for their child. They must also
understand how to adjust the insulin dose based upon blood glucose
concentrations and carbohydrate intake.
 Hypoglycemia – Families are taught to recognize the signs and symptoms of
hypoglycemia. Detection of hypoglycemia is particularly difficult in the nonverbal
young child and infant in whom the signs of hypoglycemia are nonspecific. Parents
are trained to check a blood glucose level and, if this is too low, to intervene with
dietary measures and to visit the nearest health facility.
 Blood or urine ketones – Families are taught to check urine for ketones at times
of illness and/or if two consecutive blood glucose readings are greater than 250
mg/dL (13.9 mmol/L). This is especially important in young children or those with
a history of diabetic ketoacidosis (DKA).
The initial educational and care phase may occur either in the inpatient or ambulatory
setting. Initiate the care of most newly diagnosed children with type 1 diabetes without
ketoacidosis in the outpatient setting.
b) DIABETES EDUCATION: ONGOING MANAGEMENT

After the initial phase, the diabetes team continues to provide care, teaching, and
support to the child and family. School teachers need to be also involved.
During these sessions, the concepts that are required for glycemic control are taught
and reinforced.
These include the interaction of insulin, diet, and exercise on blood glucose
concentrations.
A management regimen specific for each patient is designed to achieve the best possible
glucose control. In addition, the clinician should explain that strict glycemic control
helps to prevent long-term sequelae of diabetes; this discussion should be repeated and
reinforced as often as necessary, particularly if glycemic control is suboptimal.
Myths and false beliefs surrounding diabetes (e.g. “catching” diabetes) should be
dispelled at diagnosis.
Diabetes education is most effective when based on self management, and is child and
parent-centred.
Ongoing education should be learner-centred, and reinforced by visual aids such as
diagrams, drawings, puppet/ toy use, written guidelines, booklets, video, DVDs
appropriate to the child’s age, maturity and environment.

Providing age-appropriate psychosocial support for the patient and the family by the
clinical team improves adherence to the management plan.
As the child grows older, education and training are directed toward increased
autonomy and self-management for the patient.
The management plan of childhood-onset type 1 diabetes depends on the child's age,
cognitive ability, and emotional maturity, which affect his or her ability to communicate
symptoms and participate in self-management.
ii. INSULIN THERAPY OF TYPE 1DM
All children with type 1 diabetes and some children with Type 2 diabetes require
insulin. The aim is to replace insulin as physiologically as possible so that bloodglucose
levels are within the target range avoiding hypoglycaemia and sustained
hyperglycaemia. Prolonged underinsulinisation results in chronic hyperglycaemia
which increases the risk of stunted growth, diabetes complications, including diabetic
ketoacidosis.
Comprehensive diabetes management includes insulin treatment, blood glucose
monitoring, nutritional management, physical activity, education, rules for sick days,
and psychosocial support
Insulin requirements
• Pre-pubertal children (outside the partial remission phase) usually require 0.7-1.0
IU/kg/day.
• During puberty, requirements may rise substantially above 1 and even up to 2
U/kg/day.
• The ’correct’ dose of insulin is that which achieves the best attainable glycaemic
control for an individual child or adolescent, without causing obvious
hypoglycaemia, and resulting in normal growth and development.
Types of Insulin (See table below)
In Ethiopia human insulin is the most commonly available form.

This comes in three forms:
• Short-acting (regular/soluble) - e.g. Actrapid, Humulin R, Insuman Rapid
• Intermediate-acting - NPH insulin – e.g. Humulin NPH, Protaphane, Insulatard
• Pre-mixed short-acting (regular) and intermediate-acting (NPH) insulins – usually
in the combination 30/70 or 25/75
Analogue Insulins are also available but are substantially more expensive.
Examples are:
• Rapid-acting - e.g. Aspart, Glulisine, Lispro
• Long-acting – e.g. Glargine, Detemir

Table: Types of insulin
INSULIN DOSE
Insulin requirement is based upon the body weight, age, and pubertal stage of the child.
 In general, the newly diagnosed child requires an initial total daily insulin dose of
0.5 to1.0 units/kg.
 Pre-pubertal children usually require lower doses, and the dose requirement may
be as low as 0.25units/kg for a variable period following diagnosis.
 Higher doses are needed in pubertal children, patients in ketoacidosis, or in
patients receiving glucocorticoid therapy.
In infants and toddlers who receive their insulin by syringe, the insulin dose may be so
small that dilution is required to allow for easier and more precise administration. The
smallest dose of insulin that can be accurately administered without dilution using a
syringe is 0.5 units.
INSULIN REGIMENS
The two most common regimens used are:
a) Twice-daily insulin using both short-acting and also intermediate-acting insulin.
(If these insulins are not always available, pre-mixed insulin can be used as an
alternative regimen).
b) Basal bolus regimen (the preferred option) - with shortacting insulin given with
main meals (usually three times per day) and intermediate-acting insulin given
once or twice daily (evening, or morning and evening).

• Insulin can also be given by an insulin pump but this is very expensive and requires
expert education to initiate and monitor therapy.
INITIATING INSULIN THERAPY IN A CHILD NOT IN DKA
Day 1
Give short-acting (regular) insulin (0.1 U/kg) every second hour until blood glucose is <
11 mmol/l, then every 4-6 hours.
If hourly monitoring of blood glucose cannot be provided, begin with half the above
dose.
Day 2 (from morning/breakfast):
Total daily dose 0.5-0.75U/kg/day.
a) TWO INJECTIONS PER DAY

• A starting point is to give two-thirds of the total daily insulin in the morning before
breakfast and one-third before the evening meal.
Class Exercise
Calculate insulin dosing for a 36kg child newly diagnosed with Type 1 DM with no signs
of DKA.
Answer:
For a 36 kg child who is started on 0.5 U/kg/day, the total daily dose is 18 Units. Two-
thirds of this is given in the morning (before breakfast) – (12 Units), and one-third
before the evening meal – 6 Units. At each injection, 1/3 is short-acting and 2/3 is
intermediate-acting.
Therefore the doses, for this 36 kg child, would be:

Intermediate-acting Short-acting
Before breakfast 8 Units 4 Units
Before evening meal 4 Units 2 Units
For mixed insulin, always think of the components separately (i.e. 10 units of mix 70/30
equals 3 units of short-acting (regular) and 7 units of intermediate-acting (NPH)), and
adjust doses as above.
b) BASAL BOLUS REGIMEN
A starting point is:
• If short-acting (regular) and intermediate-acting insulin is used, give:

 70% of the total daily dose as short-acting (regular) insulin (divided up
between 3-4 pre-meal boluses)
 30% of the total daily dose as a single evening injection of intermediate-acting
insulin
• If short-acting (regular) and long-acting analogue insulins are used, give:
 50% of the total daily dose as short-acting (regular) insulin (divided up
between 3-4 pre-meal boluses)
 50% of the total daily dose as a single evening injection of long-acting analogue
insulin. (Sometimes this dose does not last for 24 hours and then can be split
into two doses morning and evening).
The total daily dose required will generally increase as the child grows, and once
puberty ensues a higher dose per kg per day is often needed.
MIXING INSULINS IN THE SAME SYRINGE

It is very common to combine intermediate-acting and short-acting/rapid-acting
insulins, in order to cover both basal needs plus the extra need from eating.
Short-acting insulin or rapid-acting analogues can be combined with intermediate-
acting insulins (e.g. NPH) in the same syringe. Begin by injecting air into both bottles.
The short-acting insulin is generally drawn into the syringe first.
If the intermediate-acting insulin is a “cloudy” insulin, mix by tipping the vial/bottle up
and down 10 – 20 times. Do not shake the insulin as this damages the insulin. The doses
can be adapted every day according to food intake, physical activity, and blood glucose
readings.
GIVING AN INJECTION WITH A SYRINGE

1. Use insulin syringes U-100. Ensure that the syringes have adequate gradations and
that the dose is correctly understood.
2. Before injecting, check the expiry date, and the name (correct amount of the correct
insulin)
3. Pull the plunger down to let air in the syringe, equalling the amount of insulin to be
given. Inject this air into the vial.
4. Draw up the insulin

5. Take a small pinch of skin with the index finger and thumb. The pinch needs to be at
least to the depth of the needle. This is especially important in lean people,
otherwise the injection may go too deep into the muscle layer, hurt more, and
absorption will be affected.
6. Insert the needle at a 45 degree angle into the pinched-up skin to a distance of 4-6
mm. Give the injection.
7. Leave the needle in for about 5-10 seconds, then gradually let go of the skin and pull
out the needle.
8. Dispose of the syringe appropriately depending on local advice.
e.g. sharps container, tin, or strong plastic bottle.
Pinching the skin to give an insulin injection. A small pinch with the finger and
thumb is enough.
Recommended Insulin Injection sites for children and adolescents
1. Good technical skill concerning syringes/ pens is important.

2. Injections in the abdominal area are preferred with insulin absorbed more
evenly and less affected by exercise than other sites. If insulin is injected into an
area that is going to be exercising significantly, it will be absorbed quicker.
3. Children and adolescents should be encouraged to inject consistently within the
same area (abdomen, thing, buttocks) at a particular time of day, but must avoid
injecting repeatedly into the same spot to avoid lipohypertrophy.
Insulin storage
1. Unused insulin should be stored at 4-8oC in a refrigerator where available or in
some other method of cooler. In hot climates where refrigeration is not available,
cooling jars, zeer pot, earthenware pitcher (matka) or a cool wet cloth around
the insulin will help to preserve insulin activity.
2. Insulin must never be frozen.
3. Direct sunlight or extreme heat (in hot climates or in a vehicle) damages insulin.
4. Patients should not use insulins that have changed in appearance (clumping,
frosting, precipitation, or discolouration).
5. After first usage, an insulin vial should be discarded after 3 months if kept at 2-
8oC or 4 weeks if kept at room temperature.
Partial Remission or Honeymoon Phase in Type 1 Diabetes

• A few weeks after the diagnosis and initiation of insulin therapy, a period of
decreasing exogenous insulin requirement occurs
• This has been defined as insulin requirements of less than 0.5 units per kg of body
weight per day with an HbA1c < 7%.
• Ketoacidosis at presentation and at a young age reduce the likelihood of a
remission phase.
• It is important to advise the family of the transient nature of the honeymoon phase
to avoid the false hope that the diabetes is spontaneously disappearing.
• Close monitoring of blood glucose is mandatory as hypoglycemic episodes are
likely if the insulin dose is not appropriately adjusted.
• The duration of this phase is variable and may last several months to several years.
• Rising blood glucose levels, HbA1C, and increasing exogenous insulin need
indicates the end of this phase.
iii. MONITORING GLYCEMIC CONTROL
Daily blood glucose levels are used to monitor glycemic control and adjust management.
The most widely used clinical test to evaluate long-term glycemic control is blood
glycated hemoglobin (also called hemoglobin A1C).
Both in children and adults, the goal of management is to maintain glucose control as
near to normal as safely possible (ie, balance the risks of long-term complications of
diabetes and hypoglycemia).
Currently Recommended Targets for children and adolescents :

 HbA1C of <7.5 percent , Or
 blood glucose levels 90 to 130 mg/dL before meals, and
 blood glucose levels 90 to 150 mg/dL at bedtime and overnight.
However considering the limitation of close monitoring of blood glucose in Ethiopia

older age based recommendations may still be more appropriate.
Age Pre meal BG 30 days average BG Target HbA1c
level(mg/dl) level (mg/dl)
<5 years 100-200 180-250 7.5–9.0
5-11 years 80-150 150-200 6.5–8.0

11-15 years 80-130 120-180 6.0–7.5
15 -18 years 70-120 100-150 5.5-7
More or less stringent goals may be appropriate for individual patients, depending on
their personal history of severe hyperglycemia and severe hypoglycemia, hypoglycemia
unawareness, known micro- and macrovascular complications, and lifestyle or
psychosocial considerations.
BLOOD GLUCOSE MONITORING

– Blood glucose monitoring is essential in the safe management of childhood and
adolescent diabetes to help prevent acute and chronic complications, and also
educate and empower the child and family.
– When possible, blood glucose monitoring should be available for all children with
diabetes.
– Blood glucose monitoring should ideally be carried out 4-6 times a day, however,
this is dependent on the availability of testing strips. Even a couple of tests a week
can assist management, and two tests per day gives much useful information.
– Ideally a record should be kept of blood glucose tests.
– Should test strips be scarce, it is best to test at different times of the day a few days a
week rather than the same time each day.
Interpretations of Blood Glucose Level Measurements

Patterns of BGLs are more important than a single BGL.
• If a pre-meal BGL is always high, the preceding dose of intermediate or long-acting
insulin is insufficient.
• If the pre-meal BGL is always low, the previous dose of intermediate or long-acting
insulin is too high.
• If a pre-meal BGL is sometimes very high and at other times very low, either
insulin, food or exercise are not consistent and should be reviewed.
• If the BGL 2 hours after the meal is too high, the meal dose of short-acting
(regular) insulin was too low.

• If the BGL 2 hours post-meal is too low, the previous meal dose of short-acting
(regular) insulin was too high.
HbA1c
• HbA1c (glycated haemoglobin) provides information about average blood glucose
levels over the last 2-3 months. This test measures the amount of glucose that
attaches to haemoglobin and this inturn depends on how much glucose is in the
bloodstream.
• Ideally HbA1c is measured four times per year. If resources are limited, less
frequent measurements are still helpful
• The target HbA1c for all age-groups is a value less than 7.5%.
• HbA1C Vs estimated Average Glucoses (American Diabetes Association conversion
factor)
HbA1C 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5 11 11.5

Estimated 111 126 140 154 169 183 197 212 226 240 255 269 283
Average
Glucose
(mg/dl)
iv. NUTRITIONAL MANAGEMENT & GROWTH MONITORING

• Children with diabetes need a healthy diet with food in amounts and proportions
appropriate to the age and stage of growth.
• Nutritional advice should be adapted to cultural, ethnic and family traditions as
well as the cognitive and psychosocial needs of the individual child.
• Encourage the child to take the right dose of insulin for the right type and amount
of food, and to eat the right amounts for that dose of insulin, at the right time.
• Insulin doses must be matched to the carbohydrate content of the food consumed,
or alternatively the carbohydrate content of food consumed must be matched to
the timing and the type of insulin injections.
• Nutritional advice should address food availability, diet, food intake and physical
activity patterns.
• Excessive restriction of carbohydrate intake to lower blood glucose levels should
be avoided.
• Sugary soft drinks or foods with high levels of saturated fat should be avoided.
• Prevention and management of hypoglycaemia, particularly before, during and
after exercise should be addressed.
• Education should include preventing hypoglycaemia.
• Ideally there should be an experienced pediatrician in the diabetes team.
• Many patients have experienced weight loss when diabetes is first diagnosed. The
lost weight is generally regained during the first few weeks of therapy due to
insulin, hydration, and adequate energy intake. During this time of increased
consumption, children often require large amounts of insulin to control their blood
glucose levels.

• After the weight loss is corrected, ongoing assessment of growth (eg, weight,
height, body mass index [BMI]) is necessary to monitor adequacy of dietary intake
and glycemic control.
• Unexpected weight loss may be a sign of
1) illness (infections,etc.),
2) insulin omission, or
3) an eating disorder.
v. PHYSICAL ACTIVITY
 Any physical activity including exercise is very beneficial and should be encouraged.
Diabetes should not be a barrier to participating in exercise.
 Preparations are needed as exercise may result in hypoglycaemia. Where possible,
patients and families should be given tailored advice about what and how much
carbohydrate to take before, during, and after exercise, as well as advice about
insulin adjustment. Some children and adolescents should snack before activities
while others may do better snacking mid-activity or even afterwards.
 For short, high-intensity activity, the snack should preferably be a fluid-based high
energy drink. For a long duration of low-intensity activity, it should be food that is
digested more slowly – e.g. fruit.
 Where monitoring is available, blood glucose needs to be measured before exercise,
during and following exercise.
 Approximately 1-1.5 g carbohydrate/kg body weight/hour should be consumed
during strenuous exercise the child is unable to monitor and reduce their insulin
dosage.
 Hypoglycemia is more likely to occur with prolonged or intense physical activity. It
often occurs during or shortly after exercise but is possible up to 24 hours
afterwards (increased insulin sensitivity). Risk of post-exercise nocturnal
hypoglycemia is high. The evening dose of intermediate- or long-acting insulin often
needs to be decreased after exercise in the afternoon or evening, especially if not
exercising on a regular basis. Particular care should be taken that the bedtime blood
glucose level is > 7.0 mmol/L (125 mg/dl).
 Sugar-free fluids should be consumed to avoid dehydration.
 Where unaccustomed exercise is being taken, e.g. at a diabetes camp, reduction in
total daily dose of insulin (20- 50%) is advised to avoid hypoglycaemia.
 Insulin is absorbed quicker when it is injected near to muscles that are being
exercised – e.g. legs in soccer. Hypoglycaemia is then more likely to occur.
 If blood glucose levels are high (>15mmol/l, 270 mg/dl) with
ketonuria/ketonaemia, exercise could be dangerous and should be avoided. Give
approximately 0.05 U/kg, or 5% of total daily insulin dose as short-acting (regular)
(or rapid-acting analogue) insulin and postpone exercise until ketones have cleared.
 If ketones cannot be measured, a child who is feeling nauseous should not
participate in exercise.

 Children and young people engaged in competitive or more serious sport will
require additional support. This should include detailed discussion about the
activity and tailored advice on insulin and food adjustments.
vi. PSYCHOSOCIAL ISSUES ASSESSMENT AND MANAGEMENT
The period following the diagnosis of diabetes is a very difficult time for families and
they may experience varied feelings including shock, denial, anger, sadness, depression,
fear and guilt.
Children may also feel that having diabetes is a punishment for them doing something
wrong.
Adjusting to diabetes takes time, and dealing with it is a daily challenge. It is important
to remember that every family is different and manages in different ways.
The diabetes team should routinely assess how the child and family are coping.
Strategies to help the child and their family cope with diabetes:
• Encourage the family to learn about diabetes.
• Encourage the family to share their diabetes knowledge with family and friends to
engage support.
• Depending on their age and capability, encourage the child to become involved in
some of their care.
• Encourage the child to talk to others with diabetes – children often benefit from
participating in a support group or camps for children or teens with diabetes.
• Encourage the child to talk about their feelings.
• Encourage the parents to be positive.
• Once settled into a routine, encourage parents to try to re-focus on their child as a
whole person - not just on the diabetes.
• Children and adolescents should be assessed for depression, anxiety, school
absences, family conflict, and other mental health challenges during most routine
visits for diabetes care.

ACUTE COMPLICATIONS OF TYPE 1 DM
1. HYPOGLYCAEMIA
Definition
Hypoglycemia occurs when the blood glucose level is ≤3.9 mmol/L (70 mg/dl) or where
there are symptoms of a hypo at a level close to this.
Causes
The main causes of hypoglycemia are:
• Delayed or missed meals (review reasons for this)

• Physical activity (where possible BGL should be checked prior to exercise, and
extra carbohydrates should be eaten based on the BGL and the expected intensity
and duration of the exercise).
• Not eating enough carbohydrate (assess timing, amount and peak glucose effect of
food eaten)
• Too much insulin (assess insulin profile, time of administration, peak and intensity
of action)
Symptoms and signs of Hypoglycemia

Autonomic Symptoms Symptoms of Neuroglycopenia
Trembling/shaking Inability to concentrate
Rapid heart rate Blurred or double vision
Palpitations Slurred speech
Sweating Confusion/vagueness
Pallor Dizziness/unsteady gait
Hunger Loss of consciousness
Nausea Seizures
Mild Hypoglycaemia occurs when the patient can recognize hypoglycaemia and is able
to self-treat without assistance of others. BGL is ≤ 3.7mmol/L or ≤ 70mg/dl.
Severe Hypoglycaemia is when the patient either loses consciousness or has a seizure
associated with low blood glucose, or is unable to help him/herself.
TREATMENT OF HYPOGLYCAEMIA
Always stay with the person with hypoglycaemia
STEP 1
Give fast acting glucose immediately – 0.3g/kg. An example for a 50kg child – giving 15
gm carbohydrate, is:
• 150-200 ml (1/2 a cup) of a sweet drink e.g. cola or fruit OR
• 3-4 teaspoons of sugar or honey OR
• 6 large or 12 small jelly beans

STEP 2
Follow with one exchange or serve of slow acting carbohydrate (10- 15 gm = one slice of
bread/2 plain biscuits OR one apple OR one banana OR 250ml or one cup of milk) to
maintain the BGL OR if a meal or snack is due within 30 minutes, give that meal or snack
earlier.
Where BG testing equipment is available, re-test blood glucose 10-15 minutes after
treatment, to confirm the BGL is within normal limits. If the BGL remains low, repeat
Step 1.
If the patient is unconscious or convulsing and unable to take anything by mouth, lie
them on their side and keep their airway clear – i.e. the ABC of resuscitation – airway,
breathing, circulation.
Severe hypoglycaemia with loss of consciousness ± convulsions (or if the child is

vomiting)
Give intravenous glucose carefully and slowly over several minutes, using 10% or 25%
glucose/dextrose solution (or 50% if these are unavailable). Total dose over a several
minutes is 0.2-0.5 gm / kg of glucose/dextrose. 50% Dextrose is very hypertonic, and so
if it is given it should be administered slowly into a large vein.
HYPOGLYCAEMIA UNAWARENESS
Hypoglycaemia unawareness is defined as neuroglycopenia occurring before autonomic

activation and can be associated with reduced awareness of the onset of hypoglycaemia.
It occurs when a single, or multiple, hypoglycaemic episode(s) lead to a significant
decrease in neuro-hormonal counter-regulatory responses causing unawareness of
hypoglycaemia. Hypoglycaemia unawareness is more common in those who maintain
generally lower blood glucose levels. Loss of awareness of hypoglycaemia can be
reversed by avoiding hypoglycaemia for 2-3 week. Aim is for hypoglycemia awareness
to come back by itself.
2. MANAGEMENT OF DIABETIC KETOACIDOSIS

Diabetic Ketoacidosis (DKA) occurs when there is profound insulin deficiency. It
frequently occurs at diagnosis and also in children and youth with diabetes if insulin is
omitted, or if insufficient insulin is given at times of acute illness.
The biochemical criteria for DKA are:

• Hyperglycaemia (blood glucose >11mmol/l (~200 mg/dl))
• Venous pH <7.3 or bicarbonate <15 mmol/l
• Ketonaemia and ketonuria

DKA results in vomiting, abdominal pain, flushed cheeks, acetone (sweet) smell on
breath and dehydration with continued polyuria. Breathing at first is rapid and shallow
and later deep sighing respirations (Kussmaul breathing). The level of consciousness
decreases and coma can ensue.
DKA is a medical emergency and correction of the clinical and chemical changes must
occur gradually to prevent the complications associated with DKA, particularly cerebral
oedema. Fluid replacement is initially more important than insulin therapy, as early
mortality is due to dehydration and shock rather than hyperglycaemia. Insulin therapy
is needed to correct the acidosis and hyperglycaemia.
Treatment should be initiated at the healthcare site of first contact, and the child should
be transferred as soon as possible to the best available site of care with diabetes
experience.
If insulin is not available at the healthcare site, transfer is urgent, however fluid
treatment must be initiated immediately.
Managing DKA includes the following components:

• Initial assessment and monitoring
• Correction of shock
• Correction of fluid replacement
• Insulin treatment
• Potassium replacement
• Role of bicarbonate
• Treatment of infection (if present)
• Management of cerebral oedema
• Monitoring of the child
• Transitioning to subcutaneous insulin
Use the DKA Flow chart
DKA FLOW SHEET
Dat Time BP PR RR RBS Urine Urine Electrolyte Neurologic Insulin Fluid

e hrly glucos ketene K + every status dose input
e every 2-4 hourly (GCS) and
2 hrly 2 hourly outp
hourly ut
Refer to DKA Management Algorithm and Protocol

3. SICK DAY MANAGEMENT IN TYPE 1 DM
Many illnesses, especially those associated with fever, raise blood glucose levels
because of the effect of stress hormones. The increased resistance to insulin can
increase ketone production.
Illnesses with gastrointestinal symptoms (e.g. diarrhoea and vomiting) may lead to
lower blood glucose levels and hypoglycaemia due to decreased food intake, poor
absorption and changes in intestinal motility.
Sick day management should be an integral part of the initial education of the child and
family, and then reinforced at regular intervals.
Management
1. Do not stop insulin during sick days, even though the child or adolescent is ill and
not eating normally. The insulin dose may frequently need to be increased or
decreased, based on the blood glucose level and food intake, but insulin should not
be stopped. If there are no facilities for home monitoring of glucose and ketones, the
child or adolescent should be taken to a healthcare facility for regular testing.
2. Evaluate and treat the acute illness.
3. Increase monitoring of blood glucose levels to 3–4 hourly (and more frequently if
the glucose level fluctuates widely or changes rapidly).
 Monitor ketones 1-2 times per day if possible.
 Check weight if scales are available as a measure of dehydration.
 If blood glucose is high with ketones, more insulin is needed.
 If blood glucose is low with ketones, (i.e. “starvation ketosis”) more sugary
drink is needed before extra insulin can be given.
 If home glucose and/or ketone monitoring is unavailable, frequent contact with a
health professional or clinic review is advisable.
4. Supportive care includes:
 Adequate fluid intake. Fever and hyperglycaemia can cause increased fluid
losses. Oral rehydration fluid provides a source of both fluid and energy.
 Easily-digested foods when there is loss of appetite.
 Treating fever with anti-pyretics and treating or prevent vomiting by
frequently offering small volumes of fluid to drink.
 Admitting the child or adolescent to a healthcare facility if these supportive
measures cannot be ensured as an out-patient.
5. Additional insulin is usually necessary to control blood glucose (unless the illness
causes hypoglycaemia)
a. Elevated blood glucose results, with absence or small amount of ketones:
Give: 5-10% of total daily dose of insulin (or 0.05-0.1 U/kg) as short or rapid-
acting insulin repeated every 2-4 hours. Total Daily Dose is the sum in units
of all insulin injections on a normal day.
b. Elevated blood glucose results with moderate or large amount of ketones.

Give: 10-20% of total daily dose of insulin (or 0.1 U/kg) as short or rapid-
acting insulin (if available) repeated every 2-4 hours.
6. When vomiting occurs in a child with diabetes, it should always be considered a sign
of insulin deficiency (impending ketoacidosis) until proven otherwise.
7. Strenuous exercise should be avoided
8. Consider admission under the following circumstances:
 Very young children with diabetes, who may become dehydrated more
rapidly than older children or adolescents.
 Parent’s inability to check blood glucose at home
 If supportive care cannot be ensured at home
 If the acute illness is severe
 If there is persistent ketonuria

MANAGEMENT OF CHRONIC COMPLICATIONS
Diabetes complications can lead to severe morbidity and mortality. The most important
principle in prevention of complications is to achieve as near normal glycaemic control
as possible by intensive education and treatment from diagnosis.
Chronic Complications may include:

1. Underinsulinisation leading to growth failure and pubertal delay
2. Retinopathy resulting in visual loss and blindness
3. Diabetic nephropathy causing hypertension and renal failure
4. Neuropathy causing pain, paraesthesia, muscle weakness and autonomic
dysfunction,
5. Macrovascular disease causing cardiac disease, stroke and peripheral vascular
disease with limb loss.
Screening for subclinical complications, with early treatment can delay progression to
clinical complications. Other known risk factors are high blood pressure, smoking and
hyperlipidaemia.
Once the family is well trained and a management plan is established and stable follow-
up at least every three months to review glycemic control and adjust management as
needed is recommended.
STANDARD SCREENING REGIMEN:

1. Weight should be measured at each visit, and Height annually. Pubertal status
should be noted at relevant ages.
Height and weight should be monitored carefully at least twice a year and
plotted on growth curves so that deviations can be detected early and therapy
appropriately adjusted. Most children with T1DM grow normally.
However, poor glycemic control can result in poor linear growth, poor weight
gain, and/or delayed skeletal and pubertal development.
Conversely, treatment with excessive insulin and/or excessive caloric intake can
lead to excessive weight gain. If obesity develops, this can lead to insulin
resistance, which complicates diabetes management.
2. HbA1c is ideally measured every three months. Target level is <7.5% (58
mmol/mol)
3. Blood pressure should be measured at least annually
o Antihypertensive medication should be introduced if blood pressure is
consistently >95th centile or > 130/80 mmHg.
o Angiotensin converting enzyme (ACE) inhibitors (such as enalapril,
captopril) or Angiotensin II receptor blockers (ARB) are recommended
treatment and have been effective and safe in children in short-term
studies, but are not safe during pregnancy.

o Other antihypertensive agents, such as calcium channel blockers and
diuretics can be used if ACE inhibitors are unavailable.
4. Eyes and visual acuity should be checked for retinopathy and cataracts after
two years diabetes duration, and annually thereafter.
o Minimum assessment for retinopathy should be by visual acuity
assessment and where at all possible ophthalmoscopy through dilated
pupils by an experienced observer.
o Where available, assessment for retinopathy should be by fundal
photography as well.
o Abnormalities should be managed by an ophthalmologist.
5. Peripheral and autonomic neuropathy should be assessed by history, physical
examination and sensory tests for vibration, thermal sensation or light touch.
o Tools include cotton wool, low-frequency tuning forks and
monofilaments.
o Feet should be examined for neuropathy, infections, ulcers etc after two
years diabetes duration, and annually thereafter.
6. Urinary protein should be measured after two years diabetes duration, and
annually thereafter. (Persistent microalbuminuria has been shown to predict the
progression to end stage renal failure and is associated with an increased risk of
macrovascular disease).
If possible, microalbuminuria should be measured annually by:
o Timed overnight or 24 hour urine collections (AER).
o First morning urine albumin/creatinine ratio (ACR).
If assessment of microalbuminuria is not available, dipstick urine protein
measurement can be done. This only shows microalbuminuria (>500mg/day)
Persistent micro- or macroalbuminuria should be treated with ACE inhibitors

(or ARB blockers if there are side-effects from ACE inhibitors (e.g. persistent
cough)). Other causes of proteinuria (such as urinary tract infection or
schistosomiasis) should be excluded.
7. Fasting blood lipids should be performed when diabetes is stabilised in

children aged over 12 years. If there is a family history of hypercholesterolaemia,
early cardiovascular disease, or if the family history is unknown, screening
should start at age 2 years.
o If normal results are obtained, screening should be repeated every 5
years.
o Target for LDL-C should be lower than 2.6 mmol/l (100 mg/ dl). If
interventions to improve metabolic control and dietary changes cannot
lower LDL-C to target levels, statins should be considered although long-
term safety is not established in children.
8. Smoking is totally contraindicated in diabetes as it increases complications
rates.

C. TYPE 2 DM IN CHILDREN AND ADOLESCENTS
Type 2 diabetes is characterized by insulin resistance (the insulin produced works less
effectively) and often also insufficient insulin production. It is increasingly being seen in
children, particularly older children..
Children with type 2 diabetes usually lack the autoimmune antibodies seen in type 1
(although there can be overlap between the two conditions). They commonly have
acanthosis nigricans (thickened and darkened skin at the base of the neck and in the
axillae). Other features of the metabolic syndrome may also be present.
RISK FACTORS FOR TYPE 2 DM IN CHILDREN

The following factors are associated with an increased risk for childhood onset T2DM:
• Obesity
– Overweight – BMI ≥85th and <95th percentile
– Obesity – BMI ≥95th percentile
• Positive family history
• Specific racial and ethnic groups
• Female gender
• Conditions associated with insulin resistance
AGE AND GENDER
Girls are more likely than boys to develop T2DM during adolescence.
About 40 percent of pediatric Type 2 DM cases occur between 10 and 14 years of age,
and the remaining 60 percent between 15 and 19 years.
During puberty, insulin sensitivity decreases by approximately 30 percent, related to
the increased activity of growth hormone.
CLINICAL PRESENTATION
Childhood type 2 diabetes mellitus (T2DM) can present in several ways:
 Asymptomatic – Approximately 40 percent
 Symptomatic (eg, polydipsia and polyuria) without ketonuria or acidosis – 57 to
70 percent
 Diabetic ketoacidosis (DKA) – 5 to 13 percent
 Hyperglycemic hyperosmolar state (HHS) – Uncommon but serious
SCREENING FOR TYPE 2 DM

The American Diabetes Association (ADA) recommends testing asymptomatic children
for T2DM if they meet the following screening criteria:
Overweight or obese (body mass index [BMI] ≥85th percentile) and have two or
more of the following additional risk factors :
• T2DM mellitus in a first- or second-degree relative
• Member of a high-risk racial/ethnic group: Native American, African American,
Latino, Asian American, or Pacific Islander

• Signs of insulin resistance or conditions associated with insulin resistance (eg,
hypertension, dyslipidemia, acanthosis nigricans, polycystic ovary syndrome
(PCOS), or small for gestational age birth weight)
• Maternal history of diabetes or gestational diabetes during the child's gestation
The ADA recommends beginning testing at age 10 years or at onset of puberty

(whichever comes first), and repeating the screening every three years.
DIAGNOSIS OF TYPE 2 DM
The diagnostic criteria are the same as those used in adults. Unless unequivocal
symptomatic hyperglycemia is present, the diagnosis should be confirmed by repeat
testing on a different day.
MANAGEMENT OF TYPE 2 DIABETES MELLITUS IN CHILDREN AND ADOLESCENTS
It is important to optimize treatment using a combination of pharmacologic and

nonpharmacologic interventions, with close monitoring and follow-up.
GOALS — The goals of managing a child or adolescent with type 2 diabetes mellitus
(T2DM) include the following:
• To achieve and maintain near-normal glycemic control

• To improve insulin sensitivity and secretion, which results in improved glycemic
control
• To identify and treat, if necessary, comorbidities, such as hypertension,
dyslipidemia, and nonalcoholic fatty liver disease
• To prevent the vascular complications of T2DM
Type 2 diabetes often responds initially to a healthy eating plan, appropriate exercise
and weight reduction, but frequently oral hypoglycaemic medicines such as Metformin
are needed, and then later, insulin may be required
NONPHARMACOLOGIC THERAPY
Weight reduction improves glycemic control and is a crucial component of successful

management of type 2 diabetes mellitus (T2DM) in youth.
Lifestyle modifications to reduce body weight should be initiated in all patients with
this disorder.
Nutrition therapy — Individualized nutrition therapy can be effective in improving

glycemic control. Nutritional goals include:
• Improve glycemic control by balancing food intake with physical activity. This
may include providing small meals to avoid wide glycemic excursions.
• Provide a diet that reduces caloric intake but includes the nutritional
requirements for normal health and growth.

Weight goals — In children and adolescents with T2DM, the optimal goal for body
weight is a body mass index (BMI) <85th percentile for age and gender. Diet and
exercise programs help:
Dietary recommendations for Youth with Type 2 DM
• Decrease portion sizes

• Substitute a fruit or vegetable for a carbohydrate-rich food.
• Decrease or eliminate high-caloric beverages (eg, soft drinks, juices) and replace
them with water or calorie-free beverages
• Reduce the frequency of eating out and increase family meals at home.
• Nutrition therapy should include guidance on the frequency and selection of food
consumed away from home like fast food consumption.
Physical activity — Increased physical activity, independent of its effect on body
weight, improves insulin sensitivity.
Youth with T2DM should be encouraged to engage in moderate to vigorous physical

activity for at least one hour daily if possible, and to limit non-academic “screen time”
(eg, television, video game, and computer) to less than two hours daily .
PHARMACOLOGIC AGENTS
The initial and ongoing pharmacologic management of youth-onset T2DM.
• Metformin is the first-line therapy for most patients, in conjunction with

nonpharmacologic therapy . It improves insulin responsiveness by increasing
insulin-mediated glucose uptake in the peripheral tissues, and also by decreasing
hepatic glucose production. Metformin has the additional benefit of producing
modest weight loss; this is in contrast to the weight gain often associated with
insulin, thiazolidinedione, or sulfonylurea therapy.
• Insulin therapy is used for selected patients with ketosis or severe hyperglycemia, or
for patients who have mixed features of type 1 and type 2 diabetes. Insulin therapy
is helpful for these patients because they have inadequate insulin production (due to
impaired beta cell function), in addition to insulin resistance.
Current guidelines recommend that insulin be used when random plasma glucose
concentrations are ≥250 mg/dL or hemoglobin A1c (A1c) is >9 percent (75 mmol/mol).
A high proportion of individuals with T2DM ultimately require insulin therapy.
The goals for diabetes care are similar to adult targets.

INDICATORS FOR QUALITY OF DM CARE
Patient indicators
Indicators Measurement
Growth Height, weight and BMI

Puberty Age at menarche, breaking voice
Blood pressure Once in a year
Acute No of admissions for DKA

complications
Frequency of severe hypoglycaemia
Social adjustment Schooling
Number of clinic visits in last 12 months
Number of hospitalizations in last 12 months
Missed school days due to diabetes
Food security
Clinic Indicators
Indicator Measurement
Prevalence Number of children in your clinic

Acute Frequency of severe hypoglycaemia
complications
Frequency of severe hypoglycaemia in <5 year old children
Supplies Interruptions in insulin therapy
Prevention of % of patients tested for proteinuria

Micro-vascular
complications % of patients tested for HbA1c
% of patients with recorded BP
% of patients with recorded lipids
Screening for co- Thyroid disorders, celiac
morbidity

ANNEXES
ANNEX I: INSULIN INITIATION AND DOSE ADJUSTMENT IN TYPE 1 DM
Diagnosis Clinical symptoms of acute onset
polyuria, polydypsia, polyphagia and weight loss
+
FBS ≥ 126 Mg/dl, or
RBS≥ 200 Mg/dl
Indication Insulin type Starting dose Increment Alternative

dosing
Adults intermediate 0.4-0.5 unit/kg Sc 2-4 units Higher dose may

T1 DM Or long acting every week be started in
eg NPH insulin 2/3 am, 1/3 pm patients with
(If available, 1/3 of severe
the hyperglycemia
total dose should
be regular
(short acting) insulin, 2/3 of it
with the morning &
1/3 with
the evening NPH)
N.B. Patients with uncontrolled post prandial hyperglycemia, consider adding 4-5 units of regular
insulin sc twice per day to be given with NPH.

ANNEX II: ALGORITHM FOR OUTPATIENT MANAGEMENT OF TYPE 2
DIABETES
*Goal FBG 90-130 with no hypoglycemia
First visit: LIFESTYLE MODIFICATIONS (Diet and Exericse) as sole treatment if
FBG <200mg/dL.
 If FBG >200mg/dL, start metformine 500 mg BID + life style modification,
 If FBS > 350 mg/dl refer the patient to regional hospital for initiation of
insulin therapy
Immediately
After 3 months
• If FBG >130, start oral medications

Start Metformin 500mg daily with dinner, then titrate dose every 4weeks
(unless impaired kidney function)
• If tolerating, increase to 500mg BID, then1000mg BID over the next 1-3
months
After 3 months
• If FBG not at goal, add another oral medication and up-titrate every 2-4
weeks (if
feasible):
• Add Sulfonylurea (Glibenclamide 2.5mg daily or Glimepiride 1mg daily)
• titrate dose of sulfonylurea every 2-4 weeks to glibenclamide 10 mg BID or
glimipride 4mg BID
Follow up
Monitor blood glucose every two to three month, if blood glucose is

repeatedly above the goal
REFER THE PATIENT TO A PHYSICIAN TO START THIRD ORAL AGENT OR
INSULIN treatment.
Refer diabetic patients to Regional Hospitals for the following evaluations.
1. Yearly retinal screening
2. Yearly serum creatinine and urine albumin screening
3. Peripheral neuropathy screening
4. Yearly lipid screening
5. Consider starting aspirin and statin therapy if it is indicated.

ANNEX III: ALGORITHM FOR MANAGEMENT OF DIABETIC KETOACIDOSIS
(DKA) AND HYPERGLYCEMIC HYPEROSMOLAR STATE (HHS)
Diagnosis Evaluation and Monitoring
Suspicion based on clinical evaluation. Initial evaluation
Features vary among patients and may
Rapid and comprehensive clinical evaluation
include polyuria, polydipsia, fruity odor,
including vital signs (BP, PR, RR, T0), degree of
confusion, Kussmaul’s breathing, etc.
dehydration and mental status.
Diabetic Ketoacidosis (DKA)
 Immediate: serum blood glucose and
 Hyperglycemia: BG ≥250 mg/dL urine ketones, EKG evaluating for signs
 Ketonuria of severe hypokalemia
 Glycosuria  Additional testing: CBC, chemistry-Na+,
Hyperosmolar Hyperglycemic State K+, Cl, BUN, Creatinine
(HHS)  Evaluate for precipitating causes:
urinalysis, EKG, chest x-ray, etc.
 Severe Hyperglycemia: BG>600 Monitoring
mg/dL
 Change in Mental status  Random Blood sugar q 1 hr
 Moderate to severe dehydration  Urinary ketones for q2 hr
 Electrolytes, primarily Na+ and K+ q6hr,
if possible
 Mental status: expect improvement
with treatment if DKA or HHS are the
primary cause. Consider further
evaluation if not improving
 Input/output, hydration status, vital
signs
Management of DKA in Health Center
 Diagnosis: Hyperglycemia ≥ 250
mg/dl + ketoneuria ≥ 2+
 start IV Fluids with NS fast
 Give 1st dose of Regular insulin
10 IU IV and 10 IU IM
 then transfer the patient to the
hospital
119
Fluids Insulin Electrolytes
 If hemodynamically Initial Bolus Potassium
unstable, give 1 L over 30  If using continuous IV: 0.1  >5.5 mEq/Lmonitor
minutes. May IU/kg once  3.3-5.5mEq/L20-
repeat this until stable.  If continuous IV not 30mEq/L of IVF
 available: 10 IU regular  <3.3 mEq/L40-60
 If stable, administer 1-2L insulin IM and 10 u IV mEq/L of IVF and
over 2 hrs Maintenance recheck level
  0.1IU/kg/hr (continuous
 Subsequent management IV or hourly IV bolus) If lab not available:
based on vital signs, free  If BG does not by 50-70  EKG changes
water deficit and urine mg/dL within 1 hr, present20-40 mEq
output increase rate by 50% and delay insulin until
 Replace fluid deficits  Continue titration as EKG normalizes
gradually over 24-48 hrs needed  If no EKG
 changes20meq/L once
When BG
 Change fluids to 5%DNS urine function is
<250mg/dL
or 5%DWwhen BG is <250 adequate(>50 ml/hr)
 Decrease insulin to 50% of
current rate
Patients with HHS will require IVF -intravenous fluid
 Maintain BG 150-200
aggressive fluid replacement. mg/dL until resolution
(see criteria below). Adjust
insulin and 5%DW rates as
needed.
If continuous IV insulin not
available, see below for
alternative subcutaneous
protocol
Criteria for Resolution Transition to long acting insulin
DKA: HHS: Continue continuous IV for 1-2 hrs after long

acting started
 BG < 200 mg/dL  BG <250-300 mg/dL
 Negative urine ketones  Improved mental 
0.4-0.6 u/kg for insulin naïve patients
(confirm repeat in 1-2 status 
NPH/Regular: based on inpatient DM
hrs) protocol
 Hold regular insulin if patient is not
eating
 May resume home regimen if previously
on insulin
Alternative Subcutaneous Regular Insulin Protocol
(May be used when continuous infusion not available)  When BG <250 mg/dL, reduce dose by
 Initial Bolus: 10 IU IV and 10 IU IM 50%
 Maintenance: 0.1 IU/kg/hr subcutaneous q1-2 hr  Continue until resolution of DKA or HHS
or 5 IU subcutaneously q1-2 hr. (start  Continue Regular insulin 5 IU S/C for
immediately following bolus) two hrs after DKA Resolution and
transition to long acting insulin

ANNEX IV: ALGORITHM FOR MANAGEMENT OF HYPOGLYCEMIA IN DIABETIC
PATIENTS ON TREATMENT WITH GLUCOSE LOWERING AGENT OR INSULIN
Diagnosis Clinical symptoms of palpitations, weakness,
sweating, hunger pain, headache, lethargy and coma
With RBS < 70 mg/dl, even at higher value
Conscious patient  Glucose containing food like soft drinks 100-
Treatment 150 ml, 3-4 candy, 1 spoonful table sugar or
honey.
IF NO RESPONSE:
 40-50% glucose 20-40 ml IV push
 Repeat the same dose in 15 minutes if no
response
Unconscious patient  20-40 ml of 40-50 % glucose IV stat, if no
response
 Repeat after 15 minutes same dose
 then start 10% glucose solution in D/W at a
rate of 100 ml/hr,
 and transfer the patient to the hospital.
NB. If the patient gained consciousness and can take

PO meal should be taken
121
ANNEX V: DKA MANAGEMENT PROTOCOL IN CHILDREN
General Resuscitation Measures

A= If comatose inert NGT and maintain the airway
B=Give oxygen by face mask for patients with severe circulatory impairment or shock
C=Insert IV cannula and take blood sample and if the child is in shock give 20 ml/kg of 0.9 %
normal saline to the maximum of 30 ml/kg depending on the response of the child over 30
minutes
Examination
Perform a clinical evaluation to confirm the diagnosis and take weight for calculation
Vital signs
Assess the degree of dehydration
Look for signs of cerebral edema
Neurological assessment using GCS
Documentation of fluid balance and lab results
Investigation
Collect blood sample to do – RBS, Ketone, electrolytes (K +), CBC
Urine analysis – Check glucose, ketones and WBC
Blood gas analysis – PH, Bicarbonate
ECG
Blood or urine culture if there is sign of infection
Management
1. Expand intravascular volume
2. Rehydration therapy
3. Potassium replacement therapy
4. Insulin therapy
5. Avoid / Treat complications ( Hypoglycemia, Cerebral edema and Hypokalemia )
6. Treat precipitating factors
7. Follow up
DKA patient management sheet
Name--------------------------------Age-----------Weight----------Date----------------
% of dehydration-----------------Type of Resuscitation fluid-----------------------
Fluid Requirement
Bolus fluid 10 - 20 ml /kg 0.9 % N/S to be given over 1 hour. It can be repeated if necessary.
Maintenance fluid /48 hours + Deficit fluid calculated as 85 ml/kg - ( Minus ) Bolus fluid = ----
----ml/ 48 hr= with potassium 40 mmol in 1000 ml of normal saline.
K + Replacement therapy is required regardless of the serum potassium concentration.
Make sure that the child is passing urine before initiation of KCL.
Keep mannitol at the bed side (dose 0.5-1 gm/kg IV over 20 min).

INSULIN
 Start insulin infusion 1-2 hours after starting fluid management (Intravascular volume
expansion)
 Regular insulin 0.1 u/kg/hour (e.g. dilute 50 units Regular [soluble] insulin in 50 ml N/S
1 unit = 1 ml) IV infusion. Low dose iv insulin administration should be the standard of
care or
 In circumstances where continuous IV administration of insulin is not possible regular
insulin SC or IM with a dose: 0.1 unit/kg every1-2 hours can be given.
 Current practice in Ethiopia is to start with 0.5 u/kg every 6 hourly (½ IV and ½ sc
for the first dose ) then continue with 0.5 u/kg sc every 6 hourly.
 Don’t omit insulin is the key - If there is a rapid decline of glucose > 90 mg/dl /hour, you
can decrease the dose by 50%( to 0.05 u/kg/hr) and you can change the fluid to ½ N/S in 10
% D/W. Consider adding glucose even before plasma glucose has decreased to 250 mg - 300
mg/dl.
 Continue the management until the child is out of DKA ( PH > 7.3 or bicarbonate >15 mmol/l
). *In our case until the urine is ketone free.
 To prevent rebound hyperglycaemia the first SC injection should be given 1-2 hours (with
Regular insulin) before stopping the insulin infusion to allow sufficient time for the insulin
to be absorbed.
 Potassium -Can be given as potassium phosphate or acetate or chloride with a rate of
0.5 mmol/kg/hr (20-80 mmol/l of fluid)
 Acidosis -bicarbonate administration is not routine, only indicated if there is only severe
acidosis PH < 6.9.
 Oral fluids- can be introduced when there is marked clinical improvement (mild acidosis or
ketosis can be there)
DKA FLOW SHEET

Date Time BP P RR RBS/ Urine Urine Electrolyte Neurolog Insuli Fluid
R hr glucos ketene K + every ic status n dose input
e/hr every 2 (2-4 hrs) (GCS)
hourly hourly

ANNEX VI. SCREENING FOR THE HIGH RISK DIABETIC FOOT: A 60-SECOND TOOL
(2012 Sibbald)

ANNEX VII: BLOOD PRESSURE CHART FOR CHILDREN
Table Note: These values represent the lower limits for abnormal blood pressure
ranges, according to age and gender. Any blood pressure readings equal to or
greater than these values represent blood pressures in the prehypertensive, stage 1
hypertensive, or stage 2 hypertensive range and should be further evaluated by a
physician.

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FEDERAL DEMOCRATIC REPUBLIC OF ETHIOPIA

National Diabetes Mellitus Training 2016 Page 3

NAME CONTRIBUTIONS AREA OF SPECIALTY AND

Dr Asmamaw Bezabeh Reviewer Team MD,MPH, NCD Case team

National Diabetes Mellitus Training 2016 Page 4

Amha Fantaye, MD, MHA

National Diabetes Mellitus Training 2016 Page 5

ADA American Diabetes Association

National Diabetes Mellitus Training 2016 Page 6

National Diabetes Mellitus Training 2016 Page 7

ii. SCOPE OF THIS TRAINING MANUAL

Target groups for this course include:

iii. COMPONENTS OF DM & HYPERTENSION TRAINING PACKAGE

The National DM and HTN Training manual has two sections:

National Diabetes Mellitus Training 2016 Page 8

Each participant will receive the following materials:

 The national Diabetes Training Manual

vi. TRAINING OBJECTIVES

LEARNING OBJECTIVES: developing the essential knowledge, attitude and skill to

National Diabetes Mellitus Training 2016 Page 9

8:30-9:00 am RECAP SESSION

National Diabetes Mellitus Training 2016 Page 10

Time Frame Activity Facilitator

National Diabetes Mellitus Training 2016 Page 11

DEFINITION OF DIABETES MELLITUS

Diabetes is defined by the World Health Organization (WHO) as a metabolic disorder

It is accompanied by a marked propensity to develop relatively specific forms of renal, ocular,

DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS (ADA 2016)

>126 mg/dL ** > 200 mg/dL ** > 6.5% **

National Diabetes Mellitus Training 2016 Page 12

National Diabetes Mellitus Training 2016 Page 13

National Diabetes Mellitus Training 2016 Page 14

The Burden of DM IN AFRICA

The Burden of DM IN ETHIOPIA

Reasons for the rise in Prevalence of DM

National Diabetes Mellitus Training 2016 Page 15

Criteria for testing for diabetes or prediabetes in asymptomatic adults and

– DM in first or second degree relative

– Signs of insulin resistance (Acanthosis nigricans, severe obesity).

– Gestational Diabetes Mellitus in mother during child’s gestation.

The outcome of the screening will be either Normal or Prediabetes or Diabetes.

National Diabetes Mellitus Training 2016 Page 16

Pharmacotherapy for prevention of Type 2 DM

National Diabetes Mellitus Training 2016 Page 17

Total Time Allotted for UNIT 2: 1 hour and 30 minutes

THE PANCREAS AND GLUCOSE HOMEOSTASIS

Figure: The endocrine pancreas

National Diabetes Mellitus Training 2016 Page 18

Figure: Characteristic Biphasic insulin secretion after meal

CLASSIFICATION OF DM IN AN INDIVIDUAL PATIENT

National Training on Diabetes Mellitus 2016 Page 20

PATHOGENESIS OF DIABETES MELLITUS

National Training on Diabetes Mellitus 2016 Page 21

2. Pathogenesis of Type 2 Diabetes Mellitus

National Training on Diabetes Mellitus 2016 Page 22

Type 2 DM is progressive and a continuum

National Training on Diabetes Mellitus 2016 Page 23

Other Pathophysiologic changes in type 2 DM

• Altered glucagon-insulin dynamics in response to meals

National Training on Diabetes Mellitus 2016 Page 24

3. PATHOGENESIS OF GESTATIONAL DIABETES MELLITUS

National Training on Diabetes Mellitus 2016 Page 25

4. SPECIFIC TYPES OF DIABETES

National Training on Diabetes Mellitus 2016 Page 26

>126 mg/dL > 200 mg/dL > 6.5% **