Management of Diabetes Mellitus X

MANAGEMENT OF DIABETES
MELLITUS: AN OVERVIEW
DR. F. O. FINOMO MB;BS, FWACP
DEPARTMENT OF MEDICINE,
FEDERAL MEDICAL CENTRE
YENAGOA
Synopsis of Presentation
• Introduction
– Definition
– Epidemiology
– Classification
– Aetiopathology
• Management
– Type 1
– Type 2
DIABETES MELLITUS - Definition
• Group of metabolic disorders characterized by:
– Hyperglycaemia (in the absence of treatment) due to
– Deficiencies of Insulin action and/or secretion leading to
– Disturbances of metabolism of:
• Carbohydrate
• Fat
• Protein
– Associated with long term damage, dysfunction and failure
of various organs: Eyes, Kidneys, Nerves, Heart & blood
vessels
– (In other words, failure of insulin secretion, action or both
lead(s) to rise in blood glucose and other metabolic changes,
which if uncorrected cause complications.)S
– The long-term specific effects of diabetes include
retinopathy, nephropathy and neuropathy, among
other complications.
– People with diabetes are also at increased risk of
other diseases including heart, peripheral arterial
and cerebrovascular disease, obesity, cataracts
erectile dysfunction & nonalcoholic fatty liver
disease. They are also at increased risk of some
infectious diseases, such as tuberculosis &
Candidiasis.
INTRODUCTION
• Diabetes is a complex, chronic illness requiring
continuous medical care with multifactorial
risk-reduction strategies beyond glycemic
control. Ongoing patient self-management
education and support are critical to
preventing acute complications and reducing
the risk of long-term complications. Significant
evidence exists that supports a range of
interventions to improve diabetes outcomes.
Epidemiology
• DM is found in every population in the world and in all regions,

including rural parts of low- and middle-income countries. The
number of people with diabetes is steadily rising, with WHO
estimating 422 million adults with diabetes worldwide in 2014.
• The age-adjusted prevalence in adults rose from 4.7% in 1980
to 8.5% in 2014, with the greatest rise in low- and middle-
income countries compared to high-income countries
• International Diabetes Federation (IDF) estimates that 1.1
million children and adolescents aged 14–19 years have T1DM.
• Without interventions to halt increase in DM, there will be at
least 629 million people living with diabetes by 2045
• The recent figures released by IDF/ WHO indicate
that as at 2014, 422 million (8.3%) people had DM.
• This figure is expected to rise to 552 million (9.9%)
by 2030.
• Of these, around 90 to 95% of cases are of T2DM
• The expected rise in prevalence of diabetes is
mainly due to increase in diabetes risk factors,
especially physical inactivity and obesity due to
sedentary life style.
• High blood glucose causes almost 4 million deaths each
year , and the IDF estimates that the
• annual global health care spending on diabetes among
adults was US$ 850 billion in 2017.
• The effects of diabetes extend beyond the individual to
affect their families and whole societies.
• It has broad socio-economic consequences and
threatens national productivity and economies,
especially in low- and middle-income countries where
diabetes is often accompanied by other diseases.
Epidemiology - Nigeria
• Osuntokun et al (UCH, 1971) – 0.43%
• Ohwovoriole et al (Lagos, 1988)- Males 1.5%,
Females 1.9%
• Erasmus et al (Ilorin, 1989)- Urban 2.4%, Rural 1.4%
• National NCD Survey (1992)- 2.2%; highest Lagos
mainland (7.2%), lowest – Mangu, Plateau State
(rural) 0.6%
• Puepet (urban, Jos 1996)- 3.1%
• Nyenwe et al (T2DM Port Harcourt 2003) -6.8%
• Kano 1.8% (NCD Survey)
• Lagos 6 – 8% (2012 / 2013 data)
• In Nigeria about 1.6 million ( by IDF 2015)
Diabetes burden in Nigeria (million)
• National
prevalence of 4.4% 1.72M
[PERCENTAGE]
• 105,091 diabetes
related deaths
• One in every 22
adults have
diabetes
3.75M
69%
Diagnosed Type 2 DM Undiagnosed Type 2 DM
IDF Atlas 6th Edition

The Distribution of Diabetic Deaths
by Cause-PH
Disorder Percentage of Total Diabetic Deaths
by Cause
DKA 25 (21.2%)
HONKS 10 (8.5%)
Hypoglycaemia 12 (10.2%)
DMFS 23 (19.5%)
Renal failure 15 (12.7%)
Cerebrovascular disease 12 (10.2%)
Septicaemia 6 (5.1%)
Respiratory disease 6 (5.1%)
Others 9 (7.6%)
Total 118 (100%)
DKA= Diabetic Ketoacidosis, HONKS= Hyperosmolar non-ketotic state, DMFS=

Diabetes mellitus foot syndrome, ‘Others’ included malignancies, drug reactions,
hepatic disease etc.
Aetio-pathology
• Underlying characteristic common to all forms of diabetes is the
dysfunction or destruction of pancreatic β-cells .
• Many mechanisms can lead to a decline in function or the complete
destruction of β-cells (cells are not replaced, as the human
pancreas incapable of renewing β-cells after the age of 30 yrs.
• Mechanisms include genetic predisposition and abnormalities,
epigenetic processes, insulin resistance, auto-immunity, concurrent
illnesses, inflammation, and environmental factors.
• Differentiating β-cell dysfunction and decreased β-cell mass could
have important implications for therapeutic approaches to
maintaining or improving glucose tolerance . Understanding β-cell
status can help define subtypes of diabetes & guide treatment
CLASSIFICATION OF DM
Diabetes can be classified into the following general categories:
1. Type 1 diabetes (due to autoimmuneb-cell destruction, usually leading to
absolute insulin deficiency)
2. Type 2 diabetes (due to a progressive loss of b-cell insulin secretion
frequently on the background of insulin resistance)
3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or
third trimester of pregnancy that was not clearly overt diabetes prior to
gestation)
4. Specific types of diabetes due to other causes, e.g., monogenic diabetes
syndromes (such as neonatal diabetes and maturity-onset diabetes of the
young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis and
pancreatitis), and drug- or chemical-induced diabetes (such as with
glucocorticoid use, in the treatment of HIV/AIDS, or after organ
transplantation)
Other specific types of DM
1. Genetic defects of Beta-cell function e.g. MODY 1-4
2. Genetic defects of insulin action. e.g. Type A insulin
resistance
3. Diseases of exocrine pancreas. e.g. fibrocalculous
pancreatopathy
4. Endocrinopathies. e.g. Acromegaly, Cushing’s syndrome
5. Drug/chemical- induced. e.g. glucocorticoid
6. Infections. e.g. congenital rubella.
7. Uncommon forms of immune mediated DM. e.g. Stiff
man syndrome
8. Other genetic syndromes
TYPES OF DIABETES (WHO 2019)
Type 1 diabetes
Type 2 diabetes
Hybrid forms of diabetes
Slowly evolving immune-mediated diabetes of adults
Ketosis prone type 2 diabetes
Other specific types (see Tables)
Monogenic diabetes
- Monogenic defects of β-cell function
- Monogenic defects in insulin action
Diseases of the exocrine pancreas
Endocrine disorders
Drug- or chemical-induced
Infections
Uncommon specific forms of immune-mediated diabetes
Other genetic syndromes sometimes associated with diabetes
Unclassified diabetes
This category should be used temporarily when there is not a clear diagnostic
category especially close to the time
of diagnosis of diabetes
Hyperglyacemia first detected during pregnancy
Diabetes mellitus in pregnancy
Gestational diabetes mellitus
CLINICAL PRESENTATION
B) Non-Classical Features
A)Classical • Unexplained weight loss with normal
Features
appetite
• Frequent boils
• Sub-fertility
• Polyphagia- • Obstetric problems
Excessive hunger –Frequent miscarriages
–Intra-uterine fetal deaths
• Polyuria- Increased –Large/ macrosomic babies
volume & Increased –History of increased obstetric interventions
including Caesarean Sections
frequency of urine • Frequent vaginal discharge
• Ulcers that don’t heal
• Polydypsia- increased • Foot gangrene
thirst (compensatory) • Kidney failure
• Stroke
Criteria for the Diagnosis of Diabetes
Classification and Diagnosis of Diabetes:

Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S13-S27
OGTT
The Glucose Tolerance Test – WHO Criteria
Normal IFG IGT DM
(mmol/L) (mmol/L) (mmol/L) (mmol/L)
Fasting ≤6.0 6.1 – 6.9 <7.0 >7.0
2 hr Post <7.8 <7.8 7.8-11.0 ≥11.1

Glucose
load
IFG=impaired fasting glucose; IGT=impaired glucose tolerance; DM=diabetes mellitus

Screening and Diagnosis of GDM: One-Step Strategy

Staging of Type 1 Diabetes

Screening and Diagnosis of GDM: Two-Step Strategy

Pathogenesis of Type 1 DM
• HLA-associated, immune-mediated 1A)
-Concordance rate varies, up to 50%
-multiple genetic loci contributes to diabetes risk
-Both HLA DR3 and DR4- haplotypes contribute to
diabetes risk (DQ2 and DQ8 strongest susceptibility)
-strongest protective haplotype is DQB1*0602
• Autoimmunity: occurs early in life e.g. anti-GAD,
AIA, anti-Islet cell antibody
 Environmental factors: congenital rubella, CMV,
bovine milk etc.
Stages in development of type 1 diabetes
AETHIO-PATHLOGY TYPE 2 DM
• Previously – NIDDM, Adult onset diabetes
• Usually Individuals:
– Account for up to 90% of persons with diabetes ( most prevalent
endocrine disease)
– Have Insulin resistance & β cell defect
– Have relative rather than absolute insulin deficiency
– Are obese or have ↑ % body fat in esp. in abdominal region
– Seldom develop spontaneous ketoacidosis
– Undiagnosed for several years b/c hyperglycemia developes slowly
– May have insulin levels in normal range but inadequate relative to
high blood glucose level (insulin secretion defective & insufficient to
compensate for insulin resistance)
– Insulin resistance may improve with weight reduction +/-
pharmacological treatment but seldom restored to normal
TYPE 2 DIABETES
Mechanisms:
• Resistance to insulin action in target tissues
– Liver
– Muscle
– Adipose tissue
• Progressive insulin secretory defect (beta cell defect)

Metabolic Defects in Diabetes
Progressive Insulin
Secretory Defect
Pancreas
 Hepatic Glucose Hyperglycemia  Glucose Insulin

Production Uptake = Resistance
Liver Muscle
Adapted from Dr. T. Kedijang

Pancreatic Islet Dysfunction Leads to Hyperglycemia in T2DM
Fewer -cells
-cells hypertrophy
Insufficient Excessive
insulin glucagon
+ –
+
↑ Glucose
↓ Glucose ↑ HGO
uptake
HGO=hepatic glucose output; T2DM=type 2 diabetes mellitus

Adapted from Ohneda A, et al. J Clin Endocrinol Metab. 1978; 46: 504–510; Gomis R, et al. Diabetes Res Clin Pract. 1989; 6: 191–198.
TYPE 2 DM
• Believed to develop as a consequence of interaction between genetic and
environmental factors
- Strong genetic influence - type 2 DM in a first degree relative is an established risk
factor for the disease
- (The environmental factors include-a high fat diet and excessive caloric
consumption, obesity, physical inactivity, excessive alcohol consumption, smoking,
stress)
• Usually seen in middle age or beyond (after the age of 40 years) but may
be seen in younger persons
• Many patients with this form of diabetes are overweight or obese.

Risk factors- type 2
Risk factors for development of type 2 diabetes:
• Increasing age
• Family history of diabetes (i.e., parent or sibling with T2DM)
• Obesity (BMI 25 kg/m2)
• Race/ethnicity (e.g., African American, Hispanic American, Native
American, Asian American, Pacific Islander)
• Habitual physical inactivity
• Previously identified IFG or IGT
• History of GDM or delivery of baby 4 kg (9 lb)
• Hypertension (blood pressure 140/90 mmHg)
• HDL cholesterol level 35 mg/dL (0.90 mmol/L) and/or a triglyceride
level 250 mg/dL (2.82 mmol/L)
Pathogenesis of Type 2 DM
• Complex aetiology
– Genetic
– Environmental
• Genetic
– Polygenic & multifactorial
– Concordance in identical twins 70-90%
– ↑risk if one parent has DM & if both, risk up to 40%
• Environmental (Modulate phenotypic expression of disease)
– Nutrition
– Physical activity
Pathophysiology of Type 2 DM
3 main metabolic disorders:
• Insulin resistance
– 60-80% ↓glucose uptake by skeletal muscle
• ↓ Pancreatic β cell function (Insulin secretory defects)
– Altered pulsatility of insulin release
– Loss of 1st phase insulin release
– ↓insulin release in response to a glucose level
• ↑ Hepatic glucose output
Page 32
Stages of Type 2 Diabetes

Progressive Beta-cell dysfunction Oral agents require the
body to produce insulin to work.
100 At diagnosis As natural insulin production fails,
there is the oral agents also fail.
50% of
normal insulin
75 production
6yrs after
insulin
Beta Cell Production
Function 50 reduced to 25%
(%) IGT Type 2
Phase 1 Type 2
25 Phase 3
Postprandial
Hyperglycemia Type 2
Phase 2
0
-12 -10 -6 -2 0 2 6 10 14
Years From Diagnosis
Adapted from Lebovitz HE. Diabetes
06/28/2021 Reviews.
Novo 1999;7(3):139–153.
Nordisk NovoMix 30 <presenter
32
name> <reference>
Stages in DM
• Normal glucose tolerance
• IGT and/or IFG (impaired fasting glycemia)
• Diabetes mellitus:
 A). Not insulin requiring
 B). Insulin requiring for control
 C). Insulin requiring for survival
COMPLICATIONs OF TYPE 2 DIABETES
A)Acute Complications
Result from metabolic derangements
Usually medical emergencies and result in significant morbidity
and mortality.
Include:
Diabetic ketoacidosis
Hyperglycaemic hyperosmolar state.
Lactic acidosis
Hypoglycaemia.
Chronic complications.
• Manifest 10 - 20 yrs after the diagnosis in young patients
but may present earlier in older patients.
• Microvascular disease: retinopathy, nephropathy and
neuropathy.
• Macrovascular disease: - coronary, cerebral and
peripheral vascular diseases.
• The diabetic is prone to infections of the skin and
urinary tract, boils, abscesses, moniliasis and tb
Type 2 diabetes is associated with serious
complications
Stroke
Diabetic 2- to 4-fold increase
in
Retinopathy cardiovascular
Leading cause mortality and stroke5
of blindness
in adults1,2 Cardiovascular
Disease
8/10 individuals with
diabetes die from CV
events6
Diabetic
Nephropathy Diabetic
Leading cause of
Neuropathy
end-stage renal disease3,4 Leading cause of
non-traumatic lower
extremity amputations7,8
1
UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 3The Hypertension in Diabetes
Study Group. J Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672–676.
6
Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, 1997. Blackwell Sciences. 7King’s Fund. Counting the cost.
The real impact of non-insulin dependent diabetes. London: British Diabetic Association, 1996. 8Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.
Complications of DM
• 1. Heart Disease-- leading cause of diabetes-related
deaths. 2-4x as high as those of adults without diabetes
• Stroke - two to four times higher in people with
diabetes.
• High Blood Pressure - 60 to 65 percent of people with
diabetes have high blood pressure.
• Kidney Disease ;Diabetes is the leading cause of end-
stage kidney disease, accounting for about 40 percent of
new cases.
Complications continued
• Nervous System Disease -
• 60 to 70 % of people with diabetes have mild to
severe forms of nervous system damage.
• Eg peripheral and autonomic neuropathy, carpal
tunnel syndrome and other nerve problems.
• Severe forms of peripheral neuropathy are a major
contributing cause of lower extremity amputations.
Complications continued
• Nervous System Disease -
• 60 to 70 % of people with diabetes have mild to
severe forms of nervous system damage.
• Eg peripheral and autonomic neuropathy, carpal
tunnel syndrome and other nerve problems.
• Severe forms of peripheral neuropathy are a major
contributing cause of lower extremity amputations.
Dm complications (cont)
.
• Amputations :>50% of lower limb amputations occur
among people with diabetes.
• Blindness :Diabetes is the leading cause of new cases
of blindness in adults 20 to 74 years old.
• Dental Disease: Periodontal disease occurs with
greater frequency and severity among people with
diabetes. Periodontal disease has been reported to
occur among 30 percent of people aged 19 years or
older with Type 1 diabetes.
Other complications
• Complications of Pregnancy
3 to 5 percent of pregnancies among women with diabetes
result in death of the newborn. This is two to three times the
rate for women who do not have diabetes.
Infections
• People with diabetes are more susceptible to infections.
• more likely to die of pneumonia or influenza than people who
do not have diabetes
• Suffer some peculiar infections
Comprehensive Medical
Evaluation and Assessment
of Comorbidities
STANDARDS OF CARE
Tailoring Treatment for Social Context
• Providers should assess social context, including
potential food insecurity, housing stability, and
financial barriers, and apply that information to
treatment decisions.
• Refer patients to local community resources
when available.
• Provide patients with self-management support
from lay health coaches, navigators, or
community health workers when available.
Improving Care and Promoting Health in Population:
Patient-Centered Collaborative Care
• A patient-centered communication style that
uses person-centered and strength-based
language, active listening, elicits patient
preferences and beliefs, and assesses literacy,
numeracy, and potential barriers to care
should be used to optimize patient health
outcomes and health-related quality of life.
Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation
A complete medical evaluation should be performed
at the initial visit to:
• Confirm the diagnosis and classify diabetes.
• Evaluate for diabetes complications and
potential comorbid conditions.
• Review previous treatment & risk factor control
in patients with established diabetes.
• Begin patient engagement in the formulation of
a care management plan.
• Develop a plan for continuing care.
Comprehensive Medical Evaluation
• A follow-up visit should include most components
of the initial comprehensive medical evaluation
including: interval medical history; assessment of
medication-taking behavior and intolerance/side
effects; physical examination; laboratory
evaluation as appropriate to assess attainment of
A1C and metabolic targets; and assessment of risk
for complications, diabetes self-management
behaviors, nutrition, psychosocial health, and the
need for referrals, immunizations, or other routine
health maintenance screening.
Components of the Comprehensive Diabetes Evaluation


*
≥65 years


†
May be needed more frequently in patients with known chronic kidney disease or with changes in medications that
affect kidney function and serum potassium.
#
May also need to be checked after initiation or dose changes of medications that affect these laboratory values (i.e.,
diabetes medications, blood pressure medications, cholesterol medications, or thyroid medications),.
˄
In people without dyslipidemia and not on cholesterol-lowering therapy, testing may be less frequent.

†
May be needed more frequently in patients with known chronic kidney disease or with changes in medications that
affect kidney function and serum potassium.

Referrals for Initial Care Management
• Eye care professional for annual dilated eye exam

• Family planning for women of reproductive age
• Registered dietitian for MNT
• DSMES
• Dentist for comprehensive dental and periodontal
examination
• Mental health professional, if indicated

Immunization: Recommendations
• Provide routinely recommended vaccinations for
children and adults with diabetes by age.
• Annual vaccination against influenza is
recommended for all people ≥6 months of age,
including those with diabetes.
• Administer 3-dose series of hepatitis B vaccine to
unvaccinated adults with diabetes aged 19-59 years.
• Consider administering 3-dose hepatitis B vaccine to
unvaccinated adults with diabetes ages ≥ 60 years.
Immunization: Recommendations (2)
• Vaccination against pneumococcal disease,
including pneumococcal pneumonia, with 13-
valent pneumococcal conjugate vaccine
(PCV13) is recommended for children before
age 2 years. People with diabetes ages 2-64
years should also receive 23-valent
pneumococcal polysaccharide vaccine
(PPSV23). Ag age ≥65 years, regardless of
vaccination history, additional PPSV23
vaccination is necessary.
Common Comorbidities
• Autoimmune Diseases (T1D) • Hearing Impairment
• Cancer • HIV
• Cognitive Impairment/ • Low Testosterone (Men)
Dementia
• Obstructive Sleep Apnea
• Fatty Liver Disease
• Periodontal Disease
• Pancreatitis
• Psychosocial/Emotional
• Fractures Disorders

Guide to Diagnosis of Type 1 DM
• Generally < 30 years of age at presentation

• Rapid onset
• Moderate-to-severe symptoms
• Lean
• Significant weight loss
• Ketonuria or ketoacidosis
• Low fasting or post-prandial C-peptide
• Immune markers
– (anti-GAD, ICA, IA-2)
Comparative Features of Type 1 and Type 2 DM
Type 1 Type 2
Age of onset <40 yrs >50 yrs
Duration of symptoms Weeks Months to years
Body Weight Normal or low Obese
Ketonuria Yes No
Rapid Death without insulin Yes No
Auto-antibodies Yes No
Diabetic complications at No 25%
diagnosis
Family History of Diabetes Uncommon Common
Other autoimmune diseases Common Uncommon
MANAGEMENT
• LIFESTYLE
• PHARMACOLOGIC
GOALS
• Save life
• Alleviate symptoms
• Achieve good control to minimize long-term
complications
• Avoid iatrogenic side effects such as hypoglycaemia
• Reduce Morbidity & Mortality
LIFESTYLE/NON-PHAMACOLOGICAL
MANAGEMENT
Education
• Remains kernel of management
• Main goal is patient empowerment:

– Self-monitoring of blood glucose, blood pressure
– Immediate management of hypoglycaemia
– Foot care and foot wear
– Cooperation with physician in meeting goals
– Lifestyle adjustments
Diabetes Self-Management Education & Support (DSMES):
Recommendations
• All people with diabetes should participate in DSME to facilitate
the knowledge, skills, and ability necessary for diabetes self-care
and in DSMS to assist with implementing and sustaining skills and
behaviors needed for ongoing self-management.
• 4 critical times to evaluate the need for DSMES:
– diagnosis,
– annually,
– when complicating factors arise, and
– when transitions in care occur.
• Facilitating appropriate diabetes self-management and improving
clinical outcomes, health status, and quality of life are key goals of
DSMES to be measured and monitored as part of routine care.
Lifestyle Management:
Recommendations: Physical Activity
• Adults with type 1 and type 2 diabetes should engage in 2-3
sessions/week of resistance exercise on nonconsecutive days.
• All adults, and particularly those with type 2 diabetes, should decrease the
amount of time spent in daily sedentary behavior. Prolonged sitting
should be interrupted every 30 min for blood glucose benefits, particularly
in adults with type 2 diabetes.
• Flexibility training and balance training are recommended 2–3 times/week
for older adults with diabetes. Yoga and tai chi may be included based on
individual preferences to increase flexibility, muscular strength, and
balance.
Diet/ Exercise
• Decreases HGO
• Increases insulin action (improve insulin action)
• Increases insulin secretion (improve insulin secretion)
• Individualized exercise
• Ideal diet
 protein: 10 – 20% of total calories
 fat: <30% of total calories
 CHO: >50- 60%
Goals of Nutrition Therapy
1. To promote and support healthful eating patterns, emphasizing a
variety of nutrient-dense foods in appropriate portion sizes, to
improve overall health and to:
– Achieve and maintain body weight goals
– Attain individualized glycemic, blood pressure, and lipid goals
– Delay or prevent the complications of diabetes
2. To address individual nutrition needs based on personal & cultural
preferences, health literacy & numeracy, access to healthful foods,
willingness and ability to make behavioral changes, & barriers to
change
Lifestyle measures
• Exercise: programme planned with the Physician
– At least 150 minutes/week, 30min 5x weekly or 50min 3x/wk (if no C/I)
– Avoid weight bearing or lifting. Examples of recommended exercises include
brisk walking, jogging, bicycling, swimming.
– Individualized exercise
– Benefits: ↓HGO, ↑ Insulin action &↑ Insulin secretion
• Dietary measures: individualized, on-going
– Drastic reduction of refined sugars
– Complex carbohydrate: 50-60% of total calorie/day
– Increase fiber intake
– Protein: 10-20% of total calorie/day
– Fats: Limit intake of saturated fat and dietary cholesterol; should take <30%
of total calorie/day
– Salt: moderate – low intake
– Alcohol: discourage in overweight/obese; generally reduce, subtract amount
taken from total calorie for the day
• Weight-loss programme for overweight or obese subjects
Recommendations: Smoking
Cessation
• Advise all patients not to use cigarettes and
other tobacco products or e-cigarettes.
• Include smoking cessation counseling and
other forms of treatment as a routine
component of diabetes care.
PHARMACOLOGICAL THERAPY TYPE 1 DM
• To maintain the pleasure of eating by providing
Injectable Drugs
– Insulin & Insulin analogues
– Incretin mimetics
• GLP-1 analogue – exenatide, Liraglutide
– Amylins
TYPE 2 DM
PHARMACOLOGIC
THERAPY FOR TYPE 2
DIABETES
Recommendations: Pharmacologic Therapy For T2DM
 Metformin, if not contraindicated and if tolerated, is the preferred

initial pharmacologic agent for T2DM.
 Once initiated, metformin should be continued as long as it is
tolerated and not contraindicated; other agents, including insulin,
should be added to metformin.
 Consider insulin therapy (with or without additional agents) in
patients with newly dx’d T2DM who are markedly symptomatic
and/or have elevated blood glucose levels (>300 mg/dL) or A1C
(>10%).
American Diabetes Association Standards of Medical Care in Diabetes.

Diabetes Care Volume 42, Supplement 1, January 2019
Newer Recommendations: Pharmacologic Therapy For
T2DM
 Long-term use of metformin may be associated with biochemical
vitamin B12 deficiency, and periodic measurement of vitamin B12
levels should be considered in metformin-treated patients,
especially in those with anemia or peripheral neuropathy.
 For patients with type 2 diabetes who require an injectable drug, a
glucagon-like peptide 1 receptor agonist is preferred over insulin.
 Among patients with type 2 diabetes who have established
atherosclerotic cardiovascular disease, SGLT2 inhibitors, or GLP-
1RAs with demonstrated cardiovascular disease benefit are
recommended as part of the antihyperglycemic regimen.

Newer Recommendations: Pharmacologic Therapy for
T2DM
 Among patients with atherosclerotic cardiovascular disease at high
risk of heart failure or in whom heart failure coexists, SGLT2i are
preferred.
 For patients with type 2 diabetes and chronic kidney disease,
consider the use of an SGLT2i or GLP1RA shown to reduce the risk
of CKD progression, CV events, or both.

Recommendations: Pharmacologic Therapy For T2DM
 Metformin, if not contraindicated and if tolerated, is the preferred

initial pharmacologic agent for T2DM.
 Once initiated, metformin should be continued as long as it is
tolerated and not contraindicated; other agents, including insulin,
should be added to metformin.
 Consider insulin therapy (with or without additional agents) in
patients with newly dx’d T2DM who are markedly symptomatic
and/or have elevated blood glucose levels (>300 mg/dL) or A1C
(>10%).

Dm complications (cont)
.
• Amputations :>50% of lower limb amputations occur
among people with diabetes.
• Blindness :Diabetes is the leading cause of new cases
of blindness in adults 20 to 74 years old.
• Dental Disease: Periodontal disease occurs with
greater frequency and severity among people with
diabetes. Periodontal disease has been reported to
occur among 30 percent of people aged 19 years or
older with Type 1 diabetes.
Goals of Management in TYPE 2 DM
• To keep blood glucose as normal as possible

and prevent low blood glucose level
• To prevent the tissue damage caused by
chronic hyperglycaemia
• To keep your patient’s weight neutral or
promote weight loss in those that require it
• To provide good quality of life
• To promote independence
GENERAL STRATEGY
TYPE 2 DIABETIC PATIENTS
LIFE STYLE OPTIMISATION
N
GOALS
ORAL MONOTHERAPY FPG 4.4-6.7 mmol/l (79-121 mg/dl

PPG at 2 hours 7.8-8.9 mmol/l (140-160mg/dl)
HbA1c <7.5%
*if the upper limit of the normal range is 6.3%;
N in methods with different normal ranges than
Above (6.3%) this criterion should be calculated
As 20% above the upper limit of the range used
ORAL COMBINED THERAPY
N
INSULIN THERAPY
(MONOTHERAPY, IN COMBINATION WITH
ORAL AGENTS)
Fig. 3 N
If glycaemic goal is not reached
Continue to next treatment step
Natural history of diabetes
• Individuals destined to develop type 2 diabetes
inherit a set of genes from their parents that make
their tissues resistant to insulin
• In the liver, the insulin resistance is manifested by
increased hepatic glucose production (HGP) during
the basal state despite the presence of fasting
hyperinsulinemia
• and an impaired suppression of HGP in response to
insulin as occurs following a meal
• In muscle, the insulin resistance is manifested
by impaired glucose uptake following
ingestion of a carbohydrate meal and results
in postprandial hyperglycaemia
• As long as the β-cells are able to augment
their secretion of insulin sufficiently to offset
the insulin resistance, glucose tolerance
remains normal.
•
However, with time the β-cells begin to fail
•Initially, the postprandial plasma glucose levels and

subsequently, the fasting plasma glucose concentration
begin to rise, leading to the onset of overt diabetes.
•It is the progressive β-cell failure that determines the

rate of disease progression
• Studies have shown that the onset of β-cell
failure occurs much earlier and is more severe
than previously appreciated.
• By the time that the diagnosis of diabetes is
made, the patient has lost over 80% of his/her β-
cell function, and it is essential that the physician
intervene aggressively with therapies known to
correct known pathophysiological disturbances in
β-cell function.
• There is gradual deterioration of pancreatic β-cell
function in patients with T2DM which is reflected
into inadequate glycaemic control on the long run
Pathogenesis of B – cell failure in diabetes
1. Advancing age
2. Genes
3. Insulin resistance
4. Lipotoxicity
5. Glucotoxicity
6. Incretins
Diabetes as a progressive disease
 Up to 70-80% of beta cell function is lost at the time of

diagnosis of type 2 diabetes
 Generally, alterations in glucose handling have been present
for 5+ years prior to the laboratory diagnosis of type 2
diabetes
 Newer therapies are being targeted at mechanisms of
preserving and improving beta cell function and altering
insulin resistance while reducing risk of hypoglycemia
MONITORING OF GLYCAEMIC CONTROL
Insulin Therapy in T2DM
 The progressive nature of T2DM should be regularly &
objectively explained to T2DM patients.
 Avoid using insulin as a threat, describing it as a failure or
punishment.
 Give patients a self-titration algorithm.

Correlation of A1C with
Average Glucose
Mean plasma glucose
A1C (%) mg/dL mmol/L
6 126 7.0
7 154 8.6
8 183 10.2
9 212 11.8
10 240 13.4
11 269 14.9
12 298 16.5
These estimates are based on ADAG data of ~2,700 glucose measurements over 3 months per A1C measurement in 507 adults with
type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92. A calculator for converting A1C results
into estimated average glucose (eAG), in either mg/dL or mmol/L, is available at http://professional.diabetes.org/eAG.
ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S23; Table 8

Recommendations: Glycemic Goals in Adults
 A reasonable A1C goal for many nonpregnant adults is

<7% (53 mmol/mol).
 Consider more stringent goals (e.g. <6.5%) for select
patients if achievable without significant hypos or
other adverse effects.
 Consider less stringent goals (e.g. <8%) for patients
with a history of severe hypoglycemia, limited life
expectancy, or other conditions that make <7%
difficult to attain.
Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56

Glycemic Recommendations for Nonpregnant
Adults with Diabetes
• Postprandial glucose may be targeted if A1C goals are not
met despite reaching preprandial glucose goals.


Glycemic Recommendations for Nonpregnant Adults with Diabetes
A1C <7.0%*
(<53 mmol/mol)
Preprandial capillary 80–130 mg/dL*
plasma glucose (4.4–7.2 mmol/L)
Peak postprandial capillary plasma <180 mg/dL*
glucose† (<10.0 mmol/L)
* Goals should be individualized.

† Postprandial glucose measurements should be made 1–2 hours after the
beginning of the meal.


Care Delivery Systems
 33-49% of patients still do not meet targets for A1C,
blood pressure, or lipids.
 14% meet targets for all A1C, BP, lipids, and nonsmoking
status.
 Progress in CVD risk factor control is slowing.
 Substantial system-level improvements are needed.
 Delivery system is fragmented, lacks clinical information
capabilities, duplicates services & is poorly designed.

Promoting Health and Reducing Disparities in Populations. Diabetes Care 2017; 40 (Suppl. 1): S6-S10
Management of Hyperglycemia in Type 2
Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and
the European Association for the Study of Diabetes (EASD)
Figure 6.1—Depicted are patient and disease factors used to determine optimal A1C targets. Characteristics and predicaments toward the left justify
more stringent efforts to lower A1C; those toward the right suggest less stringent efforts. A1C 7% = 53 mmol/mol.

Glycemic Targets for complex and higher risk patients

“NEWER” DIABETES
THERAPIES
Where do they fit in?

Therapeutic Options for
Type 2 Diabetes Therapeutics over time
1995 2018
Sulfonylureas
Sulfonylureas GLP1 receptor
Insulin (NPH, Regular, ultralente) agonists
Metformin Insulin (NPH, DPP-4 inhibitors
Regular, analogues,
Alpha glucosidase Inhibitors peakless basal, etc)
Metformin Amylin analogues
TZDs Bile Acid

Sequestrants
Alpha-glucosidase Bromocriptine
inhibitors
Meglitinides SGLT2 inhibitors
Class Mechanism Advantages Disadvantages Cost
Biguanides • Activates AMP- • Extensive • Gastrointestinal Low
/ kinase experience • Lactic acidosis
Metformin •  Hepatic glucose • No hypoglycemia • B-12 deficiency
production • Weight neutral • Contraindicated if
• ?  CVD GFR < 30mL/min
SUs / • Closes KATP • Extensive • Hypoglycemia Low

Meglitinid channels experience • Weight gain
es •  Insulin secretion •  Microvasc. Risk • Poor durability
• Do NOT use
Glyburide
TZDs • PPAR-g activator • No hypoglycemia • Weight gain Mod

•  insulin • Durability • Edema / heart
sensitivity •  TGs,  HDL-C failure
• ?  CVD (pio) • Bone fractures
• ?  MI (rosi)
• ? Bladder ca (pio)
a-GIs • Inhibits a- • No hypoglycemia • Gastrointestinal Mod

glucosidase • Nonsystemic • Dosing frequency
• Slows •  Post-prandial • Modest  A1c
carbohydrate glucose
absorption • ?  CVD events
DPP-4 • Inhibits DPP-4 • No hypoglycemia • Modest  A1c High
inhibitors • Increases GLP-1, GIP • Well tolerated • ? Pancreatitis
• Urticaria
GLP-1 • Activates GLP-1 R • Weight loss • GI High
receptor •  Insulin,  glucagon • No hypoglycemia • ? Pancreatitis
agonists •  gastric emptying • ? Beta cell mass • Medullary ca
• ? CV protection • Injectable
•  satiety
Amylin • Activates amylin • Weight loss • GI High
mimetics receptor •  PPG • Modest  A1c
•  glucagon • Injectable
•  gastric emptying • Hypo w/ insulin
•  satiety • Dosing
frequency
Bile acid • Bind bile acids • No hypoglycemia • GI High

sequestrant •  Hepatic glucose • Nonsystemic • Modest  A1c
s production •  Post-prandial • Dosing
glucose frequency
•  CVD events
Dopamine-2 • Activates DA receptor • No hypoglyemia • Modest  A1c High
agonists • Modulates • ?  CVD events •Dizziness,
hypothalamic control of syncope
metabolism Nausea, fatigue
Insulin • Activates insulin • Universally • Hypoglycemia Variable
receptor effective • Weight gain
•  peripheral glucose • Unlimited efficacy • ? Mitogenicity
uptake •  Microvascular • Injectable
risk • Training
requirements
• “Stigma”
Diabetes Care, Diabetologia. 19 April 2012

Table 1. Properties of anti-hyperglycemic agents
NEWER DIABETES
MEDICATIONS
GLP-1: effects in humans
• Stimulates glucose-dependent
After food ingestion… insulin secretion
• Suppresses glucagon
secretion
• Slows gastric emptying
• Leads to a reduction of
GLP-1 is secreted from food intake
L-cells of the jejunum
and ileum • Improves insulin sensitivity
Long-term effects
That in turn… in animal models:
• Increase of β-cell mass
and improved β-cell function
Drucker. Curr Pharm Des. 2001

Drucker. Mol Endocrinol. 2003
Incretin effect on insulin secretion
Control subjects (n=8) People with Type 2 diabetes (n=14)
80 80
60 60
Insulin (mU/l)
Insulin (mU/l)
40
Incretin 40
effect
20 20
0 0
0 60 120 180 0 60 120 180
Time (min) Time (min)
Oral glucose load

Intravenous glucose infusion
Nauck et al. Diabetologia. 1986

GLP-1 Receptor Agonists
 Supraphysiologic doses of GLP-1
 Increases glucose-dependent insulin secretion
 Suppresses glucagon in fasting and postprandial states
 Slows gastric emptying
 Improves satiety
 Robust A1c lowering power ~1-2%
 Weight loss with minimal risk of hypoglycemia without concomitant
use of secretagogue or insulin
GLP-1 pathway
Endogenous GLP-1 is primarily degraded by the dipeptidyl peptidase-4

(DPP-4) enzyme within a matter of minutes
DPP-4 enzyme inhibition keeps endogenous GLP-1 concentrations
stable for longer periods of time in circulation allowing it to exert its
effects
DPP-4 inhibitors
Decrease the rapid degradation of endogenous GLP-1 to allow it to

exert its effects longer
Generally targets post-prandial glucose values with a minimal effect
on fasting glucose
Generally a very tolerable drug class with minimal potential side
effects
Hypoglycemia rare without concurrent use of sulfonylureas or insulin
Weight neutral
DPP-4 therapy “ideal patient”
Patients with renal dysfunction or intolerant of metformin as first line

therapy
In combination with metformin, particularly early into the diagnosis of
diabetes
Patients with multiple co-morbidities wishing to avoid hypoglycemia
Patients with post-prandial hyperglycemia
Sodium-glucose co-transporter 2 inhibitors
 Inhibits the SGLT2 co-transporter in the proximal tubule of the
nephron to increase glucose excretion
 Excrete roughly 60-90g glucose per day in urine
 Weight benefit by excreting calories
 Minimal risk of hypoglycemia without concomitant use of
secretagogue or insulin
 Does not require endogenous insulin secretion from the pancreas,
so can be used at any stage of disease
 Fair A1c benefit (~1%)
Sodium-glucose co-transporter 2 inhibitors
(negatives)
 Cost: ~$350-$550 per month
 Genital mycotic infections
 Potential for orthostatic hypotension (may need to decrease dose of
diuretics)
 Need to monitor renal indices due to potential for pre-renal cause
of impairment
 Not significantly efficacious in moderate or severe renal impairment
SGLT-2i “ideal patient”
 Use as second or third line agent after metformin
 Overweight or obese patient
 In a patient where risk of hypoglycemia could be a problem
 Baseline A1c 8-9%
 Patients with CV disease or heart failure history
ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM
KEY POINTS
• Glycemic targets & BG-lowering therapies must be individualized.
• Diet, exercise, & education: foundation of any T2DM therapy

program
• Unless contraindicated, metformin = optimal 1st-line drug.
• After metformin, data are limited. Combination therapy with 1-2
other oral / injectable agents is reasonable; minimize side effects.
• Ultimately, many patients will require insulin therapy alone / in
combination with other agents to maintain BG control.
• All treatment decisions should be made in conjunction with the
patient (focus on preferences, needs & values.)
• Comprehensive CV risk reduction - a major focus of therapy.
DCCT study findings
• Keeping blood sugar levels as close to normal as possible

slows the onset and progression of eye, kidney, and nerve
diseases caused by diabetes.
• Any sustained lowering of blood sugar helps, even if the
person has a history of poor control.
• Eye disease -76% reduced risk

• Kidney disease - 50% reduced risk
• Nerve disease - 60% reduced risk
• Cardiovascular disease-35% reduced risk
UKPDS
• Glycaemic control in Type 2 Dm
• (HbA1C <7%) with oral agents and or insulin
• Reduced the development of microvascular
complications particularly retinopathy by 25% compared
with conventional therapy
Glycaemic control means fewer
complications
EVERY 1% Reduced Risk*
reduction in HBA1C
21%
Deaths from diabetes
-21%
1%
- 14%
Heart attacks (-14%)
- 37%
Microvascular complications-
1% 37%
- 43%
Peripheral vascular disorders
-43%
*p<0.0001
UKPDS 35 BMJ 2000;321:405-412
THE PREVALENCE OF DIABETIC COMPLICATIONS
• DKA - mortality of 5- 10% in developed countries, 33% in developing countries.
• HHS and lactic acidosis - high mortality 40 - 50% resp in developing countries.
• Hypogly - significant cause of death in tropical Africa.
• UK and America, DM is the commonest cause of CRF, blindness and per.
neuropathy.
• Main causes DM deaths in Nigeria include uncontrolled DM, diabetic foot syn,
coronary hrt dx, stroke and nephropathy.
• In Port Harcourt, DM is the 5th commonest cause of medical deaths and
diabetic foot ulcers and sepsis are the commonest complications.
• Diabetic foot ulcer- commonest cause of non-traumatic limb amputation
worldwide.
THE MANAGEMENT OF TYPE 2 DM
• The management of type 2 DM patients should be

individualized to suit various circumstances e.g. age,
body weight etc.
The therapeutic goals are: -
• Alleviation of symptoms through normalization or
near normalization of fasting and postprandial
hyperglycaemia.
• Prevention of acute and long term complications.
Ideal treatment should:
• Reverse insulin resistance (and associated metabolic
syndrome).
• Normalize high blood glucose.
• Improve -cell glucose sensitivity and insulin secretion.
• Prevent long term complications, risk of which rises with
increasing elevation of blood glucose.
• The current management of type 2 DM hinges on non-
pharmacological and pharmacological measures.
Pathophysiological Approach
• This individualized approach (ABCDEE) has been
incorporated into the updated American Diabetes
Association (ADA) guidelines.
A – Age, B - Body weight, C - Complications (micro
vascular and macro vascular), D- Duration of
diabetes, E- Life Expectancy E – Expense.
Management
• Team Approach to DM
• Endocrinologist
• Primary Care physician
• Surgeons
– Orthopaedic
– Vascular
• Dietician
• Pharmacists
• Certified Diabetes Educator
GOALS OF TREATMENT
• Independent life
• Knowledgeable of DM
• Knowledgeable about treatment options
• Diabetic education
• Reduce risk of cardiovascular morbidity & mortality
• Reduce complications and manage when present
Goals of Management in DM
• To keep blood glucose as normal as possible

and prevent low blood glucose level
• To prevent the tissue damage caused by
chronic hyperglycaemia
• To keep your patient’s weight neutral or
promote weight loss in those that require it
• To provide good quality of life
• To promote independence
Standard Approach to the Management of T2DM:
Treatment Intensification
Insulin
Oral + Insulin + +
Oral Combination +
Diet, Exercise, Oral Monotherapy
Adapted from Riddle MC. Endocrinol Metab Clin North Am. 2005; 34: 77–98.
TREATMENT STEPS IN TYPE 2 DM
• STEP 1: Lifestyle changes- diet, physical activity
• STEP 2: Oral monotherapy
• STEP 3: Oral combination therapy
• STEP 4: Oral therapy PLUS insulin
• STEP 5: Insulin therapy
TREATMENT STEPS IN TYPE 2 DM
• STEP 1: Lifestyle changes- diet, physical activity
• STEP 2: Oral monotherapy
• STEP 3: Oral combination therapy
• STEP 4: Oral therapy PLUS insulin
• STEP 5: Insulin therapy
NON-PHARMACOLOGICAL MEASURES: -
1. Diabetes education and monitoring.
- Must be tailored to suit individual needs.
- Monitoring techniques available include
a) Home blood glucose monitoring using the glucose-meter.
Expensive, training required (daily record possible).
b) FPG or PPPG
Less involvement of patient at doctors’ office.
c) HbA1c
- Standard for long term evaluation of glycaemic control
- requires laboratory resources.
NON-PHARMACOLOGICAL MEASURES (cont)
d) Urine glucose
- Easy to apply
- Exact interpretation difficult.
- Good alternative if expensive HBGM is not available.
e) Fructosamime
- Not commonly used
- Lower cost but shorter observation period. (2-3w.) than
glycosylated haemoglobin.
Glycaemic and HbA1C targets
Parameters AACE IDF ADA
HbA1C(%) <6.5 <6.5 <7.0
Fasting Blood <110 <100 70-130

Glucose(mg/dL)
Postprandial blood <140 <135 <180
glucose (mg/dL)
AACE: American Association of Clinical

Endocrinologists
IDF: International Diabetes Association
ADA: American Diabetes Association
Two-thirds of type 2 patients are not achieving
glycemic control
NHANES1 44.5% 35.8% A1c <7%
1988-1994 1999-2000
N=1215 N=372
AACE survey
2003-20042 33%
A1c 6.5%
N=157,000 type 2
patients
39 US states included
NHANES = National Health and Nutrition Examination Survey.

1
Koro et al. Diabetes Care. 2004;27:17-20; 2 “State of Diabetes in America,” American Association of
Clinical Endocrinologists, 2003-2004. Available at:
http://www.aace.com/public/awareness/stateofdiabetes/ DiabetesAmericaReport.pdf. Accessed
One-third of patients meeting Hb A1C goal in Nigeria
30
Hb A1C<7%
nHb A1C>7%
70
Chinenye et al. Indian J Endocr Metab

2012;16:558-64
Glycemic control declines over time
with traditional monotherapy
50 44%
50%
50
Patients with A1C <7% (%)

40
Patients with A1C <7% (%)
34%
30 40 34%
20 30 24%
13%
20
10
10
0
3 years 6 years 9 years 0
3 years 6 years 9 years
Adequately Adequately
controlled and controlled and
treated with treated with
metformin* sulfonylureas†
*Overweight drug-naïve patients. †Normal weight and overweight
drug-naïve patients
Turner RC, et al. JAMA. 1999;281:2005-2012.
Many factors drive the need for intensification of
T2DM treatment
Treatment
intensifica
tion
Underlying
pathophysi
ology1
Clinical inertia is defined

as the failure to intensify
treatment when needed4
Ineffective diet
Side effects and exercise
of treatment regimens,
and poor ineffective
pharmacological
adherence1–3 agents1
Conservative
management,
limited
pharmacological
options, and
suboptimal care1
1. Adopted from Del Prato S, et al. Diabetes Care 2009;32(Suppl 2):S217–22; 2. Adopted from Grant R, et al. Diabetes Care 2007;30:807–12;
3. Adopted from Miccoli R, et al. Diabetes Care 2011;34(Suppl 2):S231–5; 4. Adopted from Khunti K, et al. Diabetes Care 2013;36:3411–7
The effects of different antidiabetic agents target
multiple defects which contribute to
hyperglycaemia in T2DM
Thiazolidinediones
Metformin
Decrease lipolysis in adipose tissue,
Decreases food
increase glucose uptake in skeletal
consumption and
muscle and decrease glucose
decreases hepatic
production in liver
glucose production
SGLT-2 inhibitors
Sulphonylureas Lower the renal
Increase insulin secretion glucose threshold to
from pancreatic -cells increase urinary
glucose excretion
Glinides DPP-4 inhibitors

Increase insulin secretion Prolong GLP-1 action leading to
from pancreatic -cells improved pancreatic islet cell
glucose sensing
GLP-1 receptor agonists

Improve pancreatic islet
-glucosidase inhibitors
glucose sensing, slow gastric
Delay intestinal
emptying, improve satiety
carbohydrate absorption
Adopted from Cheng AY, Fantus IG. CMAJ 2005;172:213–26; Adopted from Ahrén B, Foley JE. Int J Clin Pract 2008;62:8–14;
Adopted from Kim Y, Babu AR. Diabetes Metab Syndr Obes 2012;5:313–27
Pharmacologic targets of current drugs used in treatment of T2DM
Drugs Examples Pharmacological Target (s)
Sulfonylureas Glibenclamide Increase insulin secretion from pancreatic
Glipizide -cells
Gliclazide
Glimipiride
Biguanides Metformin Increase glucose uptake
and decrease hepatic glucose production
Glinides Repaglinide Increase insulin secretion from pancreatic
-cells
-glucosidase Acarbose Delay intestinal carbohydrate absorption
inhibitors
GLP-1 analogs Exendins Improve pancreatic islet glucose sensing,
slow gastric emptying, improve satiety
DPP-4 inhibitors Vildagliptin Prolong GLP-1 action leading to improved
(Galvus) pancreatic islet glucose sensing, increase
Sitagliptin glucose uptake
Note: GLP-1 (glucagon-like peptide 1); DPP-4 (Dipeptidyl peptidase-4)

COMBINATION THERAPY WITH ORAL AGENTS
• Combination therapy now being considered earlier in the management of DM
before response to monotherapy begins to decline. Such combinations offer
enhanced glycaemic control, fewer adverse effects and better outcomes.
• It is logical to combine an insulin – augmenting agent such as new sulphonylurea
compound or repaglinide with an insulin sensitizer such as the biguanide e.g.
metformin or one of the thiazolidinediones.
• Various combinations tried with good results are as follows:

• Sulphonylurea + metformin
• Sulphobylurea + Acarbose
• Sulphonylurea + Thiazolidinediones
• Rapaglinide + metformin
• Metformin + acarbose
• Metformin + thiazolidinediones.
INSULIN THERAPY
• SPECIFIC INDICATIONS FOR USE OF INSULIN IN TYPE 2 DM.

• Failure to achieve glycaemic control despite maximum doses of combination of
blood glucose lowering agents.
• Decompensation due to intercurrent events e.g. infections, acute injury etc.
• Perioperative management
• Pregnancy.
• Failure of vital organs
• Allergy or serious reactions to oral agents
• Marked hyperglycaemia at presentation
• Acute myocardial inferction.
COMBINING INSULIN AND ORAL AGENTS
Available combinations are:

1. Sulphonylurea + Insulin (best in minimizing cost)
(day time) (evening)
2. Metformin + Insulin – (best in minimizing weight gain).
3. Acarbose + Insulin
4. Thaiazolidinedione + Insulin
5. Metformin + Thiazolidinedione + Insulin
(minimize insulin resistance.)
EARLY INITIATION OF INSULIN THERAPY
• Type 2 DM xterised by deterioration of B-cell function. With increasing
incidence in younger adults who will live longer with their disease, more patients
well develop severe insulin deficiency and require insulin replacement.
• Early and effective intervention with insulin is more important than has
previously been believed.
• Insulin is the most effective treatment for lowering extremely high glucose;
important as inhibition of glucotoxicity may be beneficial in preserving functional
B-cell mass.
• Insulin may have a protective quality – against endothelial damage e.g. outcome
in myocardial infarction better with insulin therapy.
• Reducing postprandial glucose important in light of new data that show a r/ship
between PPHG and atherosclerotic risk.
STRATEGIES TO HELP PEOPLE
REMEMBER
• Check that people understand how and when

to take their medicines
• Clarify the benefits of treatment
• Keep regimens simple
• Minimize costs
• Discuss adverse effects
Suggested starting medicine
HbA1c BMI Suggested medicine
>25 Biguanide – alone or in

<9% combination
<25 1 or 2 agents from different

classes
>9% 2 medicines from different

classes or insulin
CDA 2003
DOSE ADJUSTMENT
• If goals have not been reached within 2-3

months, medication should be increased or
medication from a different class added
• Target levels should be reached within 6
months
• Insulin should be added if necessary to reach
target levels
MANAGEMENT OF CO-MORBID CONDITIONS THAT ARE
FREQUENTLY ASSOCIATED WITH TYPE 2 DM
• - Control of blood pressure.

• - Control of blood lipids.
• - Control of body weight
• - Use of platelet aggregation inhibitors
• (Low dose aspirin – 75 – 150mg/day).
• - Regular screening for chronic complications
DETECTION OF CHRONIC COMPLICATIONS
The following steps are recommended for screening for

chronic complication at least once a year.
• history of specific symptoms
• physical examination – body weight
• - height, BP
• - eyes
• - peripheral pulses
• - heart rate
DETECTION OF CHRONIC COMPLICATIONS
(cont)
• leg and feet (for calluses, neuropathy)
• Foot examination and “monofilament test” for
assessment of foot ulcer risk
• ECG
• Microalbuminuria (in overnight sample),
• Fundoscopic examination
• Serum Creatinine
• Cholesterol and lipid parameters.
• Always reinforce diabetic education e.g. Diet,
foot care
BARRIERS AND FACILITATORS TO CARE IN THE
MANAGEMENT OF TYPE 2 DIABETES
• Factors postulated as barriers or facilitators can

broadly be separated into:
• Patient
• Clinician Factors
• Organizational
Hypoglycaemia and weight gain are major limiting factors to achieving
intensive glycaemic control in people with T2DM1
Fear of hypoglycaemia is Concerns about weight

a major concern for gain and hypoglycaemia
patients, and may affect may make physicians
their attitude to reluctant to intensify
treatment.1,2 treatment.3,4
1. Adopted from Briscoe VJ, et al. Clin Diabetes 2006;24:115–21; 2. Adopted from Pramming S, et al. Diabet Med 1991;8:217–22;
3. Adopted from Cryer PE. Diabetologia 2002;45:937–48; 4. Adopted from Khunti K, et al. Diabetes Care. 2013;36:3411–7
Achieving earlier glycaemic control may generate a
“good legacy effect”, with multiple benefits for patients
9
Conventional
Median HbA1c (%)
Intensive
8
7
“Legacy effect”
6
0
UKPDS 1997 UKPDS 2007
Active treatment phase1 Follow-up phase2
At 10 years of follow-up, patients who received

initial intensive treatment showed:2
• 24% risk reduction for microvascular complications
• 15% risk reduction for myocardial infarction
• 13% risk reduction for all-cause mortality
1. Adopted from UKPDS 33. Lancet 1998;352:837–53; 2. Adopted from Holman RR, et al. N Engl J Med 2008;359:1577–89
• WHY THE NEED FOR “GOOD LEGACY
EFFECT”
Legacy effect: early glycaemic control is key to
long-term reduction in complications
Good legacy effect

Early, strict glycaemic control brings benefits,
reducing the long-term risk of microvascular and
macrovascular complications (UKPDS1)
Bad legacy effect

Achieving glycaemic control late in the disease, after a
prolonged period of poor control, does not improve long-term
risk of macrovascular complications2
Long-standing, preceding hyperglycaemia accounted for
the high rate of complications at baseline in VADT3
UKPDS=UK Prospective Diabetes Study; VADT=Veterans Affairs Diabetes Trial.
1
Holman RR, et al. N Engl J Med. 2008; 359: 1577–1589.
2
Duckworth W, et al. N Engl J Med. 2009; 360: 129–139;
3
Del Prato S. Diabetologia. 2009; 52: 1219–1226.
Clinical guidelines emphasise the importance of the
individualisation of therapeutic options for T2DM
Focus on the needs, values,

Individualise and preferences of the
blood glucose goals.1 patient, making all treatment
decisions, where possible, with
them.1,2
Assess the response to Use combination therapy

metformin monotherapy at with complementary
3 to 6 months, and intensify by mechanisms of action,
adding a second oral agent if the including drugs which
patient has not reached their target the underlying
goal.1 pathophysiology of T2DM.3
1. Adopted from Inzucchi SE, et al. Diabetes Care 2012;35:1364–79; 2. Adopted from Strain D, et al. Diabetes Res Clin Pract 2014;
http://dx.doi.org/10.1016/j.diabres.2014.05.005(Article in Press); 3. Adopted from Garber AJ, et al. Endocr Pract 2013; 19(2):327–36
The ADA/EASD position statement recommends individualising
HbA1c goals to the patient
In suitable patients, an HbA1c of <6.5% is considered optimal if it can be achieved

without significant risk of hypoglycaemia or weight gain 1–3
More stringent goal Standard goal Less stringent goal

<6.5% <7.0% <8.0%
Newly diagnosed T2DM patients Patients with long-standing T2DM

with long life expectancy and limited life expectancy
Patients are highly motivated, Patients are less motivated,

adhere to therapy, have excellent non-adherent, have poor self-care
self-care capacity, and access to capacity and limited access to
support systems support systems
At low risk of hypoglycaemia, At high risk of hypoglycaemia,

few or no comorbidities and extensive comorbidities and
no significant cardiovascular advanced microvascular or
disease macrovascular complications
1. Adopted from Inzucchi SE, et al. Diabetes Care 2012;35:1364–79; 2. Adopted from ADA. Diabetes Care
2014;37(suppl 1):S14–80; 3. Adopted from Garber AJ, et al. Endocr Pract 2013;19:327–36
PREVENTION
Type 2 Disability
Normal IGT Complications
Diabetes Death
Preclinical Clinical
state disease Complications
Primary Secondary Tertiary

prevention intervention intervention
CONCLUSION
• T2DM is a progressive disease with early onset of

complications
• Many factors drive the need for intensification of T2DM

treatment
• There is evolving evidence that the risk and progression of

diabetic complications is related to persistent poor HbA1c
control
• There is an opportunity to improve the health outcomes of

T2DM patients across the world by early intensifying
treatment with dual therapy
Destination diabetes
Timely
Individualize Avoid Clinical Intensification of
treatment Inertia Pharmacological
Treatment
Diabetes Distress
• Diabetes distress
– Very common and distinct from other
psychological disorders
– Negative psychological reactions related to
emotional burdens of managing a demanding
chronic disease
• Recommendation:
– Routinely monitor people with diabetes for
diabetes distress, particularly when treatment
targets are not met and/or at the onset of
diabetes
Standards of Medical complications.
Care in Diabetes - 2018. Diabetes Care 2018; 41 (Suppl. 1): S38-S50
Referral for Psychosocial Care
Prevention or Delay of T2DM: Recommendations
• At least annual monitoring for the development
of diabetes in those with prediabetes is
suggested.
• Patients with prediabetes should be referred to
an intensive behavioral lifestyle intervention
program modeled on the Diabetes Prevention
Program to achieve and maintain 7% loss of
initial body weight and increase moderate-
intensity physical activity (such as brisk walking)
to at least 150 min/week.
Prevention or Delay of Type 2 Diabetes:
Prevention or Delay of T2DM: Recommendations
(2)
• Technology-assisted tools including Internet-
based social networks, distance learning, and
mobile applications that incorporate
bidirectional communication may be useful
elements of effective lifestyle modification to
prevent diabetes.
• Given the cost-effectiveness of diabetes
prevention, such intervention programs
should be covered by third-party payers.

Pharmacologic Interventions for Prevention: Recommendations
• Metformin therapy for prevention of type 2 diabetes

should be considered in those with prediabetes,
especially for those with BMI ≥35 kg/m2, those aged
<60 years, and women with prior GDM.
• Long-term use of metformin may be associated with
biochemical vitamin B12 deficiency, and periodic
measurement of vitamin B12 levels should be
considered in metformin-treated patients, especially
in those with anemia or peripheral neuropathy.

Prevention of CVD in Prediabetes: Recommendation
• Screening for and treatment of modifiable risk

factors for cardiovascular disease is suggested
for those with prediabetes.

DSMES in People with Prediabetes: Recommendations
• DSMES programs may be appropriate venues

for people with prediabetes to receive
education and support to develop and
maintain behaviors that can prevent or delay
the development of type 2 diabetes.

Glycemic Targets
Assessment of Glycemic Control
• Two primary techniques are available for health
providers and patients to assess the effectiveness of a
management plan on glycemic control:
1. Patient self-monitoring of blood glucose (SMBG)
2. A1C
• Continuous glucose monitoring (CGM) also has an
important role in assessing the efficacy and safety of
treatment in subgroups of patients with T1DM and in
selected patients with T2DM.
– Data indicate similar A1C and safety with the use of CGM
compared with SMBG.
Glycemic Targets:
Glucose Monitoring: Recommendations
• Most patients using intensive insulin regimens
(multiple-dose insulin or insulin pump therapy)
should perform SMBG:
– Prior to meals and snacks
– At bedtime
– Occasionally postprandially
– Prior to exercise
– When they suspect low blood glucose
– After treating low blood glucose until they are
normoglycemic
– Prior to critical tasks such as driving
Glycemic Targets:
Glucose Monitoring: Recommendations (2)
• When prescribed as part of a broad educational program,
SMBG may help to guide treatment decisions and/or self-
management for patients taking less frequent insulin
injections or noninsulin therapies.
• When prescribing SMBG, ensure that patients receive ongoing
instruction and regular evaluation of SMBG technique, SMBG
results, and their ability to use SMBG data to adjust therapy.
Glycemic Targets:
• When used properly, CGM in conjunction with intensive
insulin regimens is a useful tool to lower A1C in adults with
type 1 diabetes who are not meeting glycemic targets.
• CGM may be a useful tool in those with hypoglycemia
unawareness and/or frequent hypoglycemic episodes.
• Given the variable adherence to CGM, assess individual
readiness for continuing CGM use prior to prescribing.
Glycemic Targets:
• When prescribing CGM, robust diabetes

education, training, and support are required
for optimal CGM implementation and ongoing
use.
• People who have been successfully using CGM
should have continued access after they turn
65 years of age.
Glycemic Targets:
A1C Testing: Recommendations
• Perform the A1C test at least two times a year in
patients who are meeting treatment goals (and who
have stable glycemic control).
• Perform the A1C test quarterly in patients whose
therapy has changed or who are not meeting glycemic
goals.
• Point-of-care testing for A1C provides the opportunity
for more timely treatment changes.
Glycemic Targets:
A1C Goals in Adults: Recommendations
• A reasonable A1C goal for many nonpregnant adults is <7%
(53 mmol/mol).
• Providers might reasonably suggest more stringent A1C goals
(such as <6.5%) for select individual patients if this can be
achieved without significant hypoglycemia or other adverse
effects of treatment (i.e., polypharmacy). Appropriate
patients might include those with short duration of diabetes,
type 2 diabetes treated with lifestyle or metformin only, long
life expectancy, or no significant cardiovascular disease.
Glycemic Targets:
A1C Goals in Adults: Recommendations (2)
• Less stringent goals (such as <8% [64 mmol/mol]) may be
appropriate for patients with a history of severe
hypoglycemia, limited life expectancy, advanced
microvascular or macrovascular complications, or long-
standing diabetes in whom the goal is difficult to achieve
despite diabetes self-management education, appropriate
glucose monitoring, and effective doses of multiple glucose-
lowering agents including insulin.
Glycemic Targets:
A1C and CVD Outcomes
• DCCT: Trend toward lower risk of CVD events with intensive
control (T1DM)
• EDIC: 57% reduction in risk of nonfatal MI, stroke, or CVD death
(T1DM)
• UKPDS: Nonsignificant reduction in CVD events (T2DM).
• ACCORD, ADVANCE, VADT suggested no significant reduction in
CVD outcomes with intensive glycemic control. (T2DM)
Care.DiabetesJournals.org
Glycemic Targets:
Approach to the Management of Hyperglycemia
more A1C less
Patient/Disease Features stringent 7% stringent
Risk of hypoglycemia/drug adverse effects

low high
Disease Duration
newly diagnosed long-standing
Life expectancy
long short
Important comorbidities
absent Few/mild severe
Established vascular complications
absent Few/mild severe
Patient attitude & expected

treatment efforts highly motivated, adherent, excellent less motivated, nonadherent, poor
self-care capabilities self-care capabilities
Resources & support system

readily available limited
Glycemic Targets:
Comprehensive targets
• Lipid profile:
– Triglycerides <150mg/dl
– LDL-C: <100mg/dl
– Total cholesterol: < 150mg/dl
– HDL-C: Males- >40mg/dl; Females > 50mg/dl
• Blood Pressure: Systolic <130mmHg; Diastolic < 80mmHg
• BMI: 20-25kg/m2
• Waist circumference: Males <100cm; Females < 88cm
Monitoring
• Urine testing
• Blood glucose – lab or glucometer
• Glycated Hb
- addition of glucose moiety to β-chain of
Hb
- test control in the last 2-3 months
• Glycosylated proteins: (fructosamine): test
control for about 2-3 weeks
Surgery
• Bariatric surgery has been shown to improve
diabetes control and, in some situations,
normalize glucose tolerance in morbidly obese
patients. It is certainly a reasonable
alternative in carefully selected patients if an
experienced team (providing appropriate
preoperative evaluation as well as technical
surgical expertise) is available.
Transplantation
• Whole Pancreas
• Isolated islet cells
References

Management of Diabetes Mellitus X

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Management of Diabetes Mellitus X

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MANAGEMENT OF DIABETES

• DM is found in every population in the world and in all regions,

Diagnosed Type 2 DM Undiagnosed Type 2 DM

IDF Atlas 6th Edition

DKA= Diabetic Ketoacidosis, HONKS= Hyperosmolar non-ketotic state, DMFS=

Classification and Diagnosis of Diabetes:

Fasting ≤6.0 6.1 – 6.9 <7.0 >7.0

2 hr Post <7.8 <7.8 7.8-11.0 ≥11.1

IFG=impaired fasting glucose; IGT=impaired glucose tolerance; DM=diabetes mellitus

Classification and Diagnosis of Diabetes:

Classification and Diagnosis of Diabetes:

Classification and Diagnosis of Diabetes:

• Progressive insulin secretory defect (beta cell defect)

 Hepatic Glucose Hyperglycemia  Glucose Insulin

Adapted from Dr. T. Kedijang

HGO=hepatic glucose output; T2DM=type 2 diabetes mellitus

• Many patients with this form of diabetes are overweight or obese.

Stages of Type 2 Diabetes

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

• Eye care professional for annual dilated eye exam

Comprehensive Medical Evaluation and Assessment of Comorbidities:

Comprehensive Medical Evaluation and Assessment of Comorbidities:

• Generally < 30 years of age at presentation

• Main goal is patient empowerment:

 Metformin, if not contraindicated and if tolerated, is the preferred

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

 Metformin, if not contraindicated and if tolerated, is the preferred

American Diabetes Association Standards of Medical Care in Diabetes.

• To keep blood glucose as normal as possible

LIFE STYLE OPTIMISATION

ORAL MONOTHERAPY FPG 4.4-6.7 mmol/l (79-121 mg/dl

•Initially, the postprandial plasma glucose levels and

•It is the progressive β-cell failure that determines the

 Up to 70-80% of beta cell function is lost at the time of

American Diabetes Association Standards of Medical Care in Diabetes.

ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S23; Table 8

 A reasonable A1C goal for many nonpregnant adults is

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

* Goals should be individualized.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

American Diabetes Association Standards of Medical Care in Diabetes.

Where do they fit in?

TZDs Bile Acid

SUs / • Closes KATP • Extensive • Hypoglycemia Low

TZDs • PPAR-g activator • No hypoglycemia • Weight gain Mod

a-GIs • Inhibits a- • No hypoglycemia • Gastrointestinal Mod

Bile acid • Bind bile acids • No hypoglycemia • GI High

Diabetes Care, Diabetologia. 19 April 2012

Drucker. Curr Pharm Des. 2001