1. Diabetes Mellitus
Epidemiology, Definition, Pathophysiology,
Diagnosis and Presentation
Sharat S. Kolke
MD, DNB, MNAMS
Asian Heart Institute and Research Center
Fauziya Hospital
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2. Epidemiology
(1)In most countries, diabetes is now one of the leading
causes of death through its effects on cardiovascular
disease: 70-80% of people with diabetes die of
cardiovascular disease.
(2)Diabetes is ranked among the leading causes of
blindness, renal failure and lower limb amputation with
type 2 diabetes accounting for 85-95% of cases of
diabetes.
(3)The total cost of caring for people with diabetes in
Europe is estimated between 28 billion and 53 billion
Euros per year
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3. The global prevalence of type 2 diabetes is
projected to increase to >330 million by 2025
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4. ….and in India
• There were 32 million diabetics in 2000
• Expected to grow up to 80 million in 2030
• Prevalence increased in urban areas from 2% in
1973 to 12% in 2000
• Beginning to increase in rural areas too!!
ICMR guidelines for management of Diabetes 2005
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5. Epidemiology
• Ethnicity
• Sex ratios
• Genetic and environmental factors
– The thrifty gene hypothesis
– The fetal origins hypothesis
• Age related prevelance
• Clinical and metabolic characteristics
– Association with obesity
– Other diabetogenic factors 5
6. Ethnicity
• Lowest prevalence are seen in less developed
countries
• High prevalence is seen in populations that have
adopted a ‘westernized’ lifestyle
• Social and behavioral changes
• Different ethnic groups have different lipid
patterns.
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8. Genetic and environmental factors
• Thrifty genotype hypothesis
• Fetal origins hypothesis (Barker and Hales)
• Other genetic factors
– Family history of T2DM is common
– Life time risk associated with one T2DM parent is
40%
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9. Age related prevalence
• Prevalence of Diabetes increases with age
– Glucose tolerance decreases with age
– Weight gain between 40s and 70s, particularly central
obesity creates Insulin resistance
..…..but recent years have witnessed the
emergence of T2DM in younger groups including
children and adolescents
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10. Clinical and metabolic
characteristics
• Association with obesity
– Obesity is directly correlated with an increased risk of
type 2 diabetes
• Dietary composition
– Increased proportion of saturated fat is linearly
associated with diabetes prevalence
– Fish diets of Eskimos and Japanese which are rich in
δ-3- poly unsaturates improve insulin sensitivity
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12. Definition
Diabetes Mellitus is a group of metabolic
disorders characterized by chronic
hyperglycemia resulting from defects of insulin
action (Insulin resistance) , insulin secretion
(β cell dysfunction/destruction) or both
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15. What is Insulin Resistance?
• Insulin resistance plays a major role in
development of T2DM.
• A reduced biological response to a physiological
amount of insulin
• Fasting hyperinsulinemia in the presence of
normal or elevated plasma glucose level implies
Insulin resistance
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16. Insulin Resistance
• Insulin resistance per se is asymptomatic
• IR precedes the onset of T2DM by 10 – 20 years
• But an additional defect in insulin secretion is
required for the development of frank T2DM
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18. Insulin Resistance
Effect of Insulin Resistance on Body Tissues
Skeletal muscle
It accounts for about 80% of glucose disposal after
glucose infusion or ingestion.
Thus in an IR state, inability to stimulate glucose
disposal by the muscles alters glucose homeostasis
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19. Insulin Resistance
Effect of Insulin Resistance on Body Tissues
Adipose tissues
IR decreases suppression of lipolysis by adipose
tissues causing increase in the levels of FFAs
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20. Insulin Resistance
Effect of Insulin Resistance on Body Tissues
Liver
Insulin suppresses hepatic gluconeogenesis partly
by reducing the flux of amino acids and FFAs from
the muscle and adipose tissue into the liver and
also by its direct effects.
In T2DM, the IR state causes excessive hepatic
glucose production due to inadequate suppression
of gluconeogenesis.
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21. Liver
Lipolysis
Triglycerides
Fatty Acid Fatty Acid
B oxidation
+ve -ve
Acetyl Co A Glucose
Triglyceride
Ketone bodies
Re - esterification
Adipose Tissue
Ketogenesis
Oxidation
in extra hepatic
tissues
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28. Pathogenesis of Type 2 DM
The progression to Type II DM
Environment Genetic
Insulin Resistance
Hyperinsulinemia
Compensated insulin resistance
Normal glucose tolerance
Beta cell exhaustion
Impaired glucose tolerance
Beta cell failure
DIABETES MELLITUS
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29. Clinical presentation of T2DM
• Estimated to occur at least 4-7 years before the
clinical presentation
• 3rd NHNES showed that 2.7% of the general
adult population and 6 % of the population
above 60 were undiagnosed diabetics
• Previously undiagnosed hyperglycemia was
discovered in 1/3rd of hospitalized patients –
Levetan et all
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30. Clinical presentation of T2DM
Nocturia
Polyuria
Dry mouth/thirst
Mean age range
Fatigue 52 (25 – 65)
66 (50 – 74)
Blurred vision
Pruritis
Paraethesias
0 20 40 60 80 30 100
Adapted from Bulpitt et al; Ruige et al
31. Clinical presentation of T2DM
• In symptomatic patients , obese individuals are
less likely to present with common symptoms
than lean individuals
• Also they are less likely to have weight loss than
lean individuals
Melton et al. Incidence of Diabetes Mellitus by clinical type.
Diabetes Care 1983;6:75 - 86
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37. Screening
• Asymptomatic individuals
– Age > 30 years
– Overweight BMI > 23 kg/m 2
– Central obesity i.e. waist hip ratio: men > 0.90
women > 0.85
– Family h/o Diabetes
– Sedentary lifestyle
– Previously identified IFG or IGT
– h/o GDM, recurrent fetal loss or delivery of large baby
– Hypertension
– Dyslipidemia
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38. Screening
• Individuals at high risk
– Any patient with symptoms of hyperglycemia
or complications of diabetes
– Adults with tuberculosis
– Patients on diabetogenic drugs
– Women with PCOS
– History of premature vascular disease
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39. Screening for Type 2 Diabetes in
children and adolescents
• Overweight (weight > 120% of ideal body weight)
plus any one of the following risk factors :-
– Family history of type 2 diabetes in first or second
degree relative
– Signs of insulin resistance or conditions associated
with insulin resistance
(viz. Acanthosis nigricans, hypertension, dyslipidemias or
PCOS).
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43. • Urine sugar should not be used alone
• Fasting and postprandial or casual plasma glucose
• Individualized regimens of SMBG
• Hb1Ac every 3- 6 months.
• Clinical examination every visit at least 3 months
• Optimizing weight, blood pressure and lipids
• Screening for long term complications like retinopathy,
nephropathy and neuropathy
• Encourage foot care
• Discourage tobacco
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45. • Ideal for every diabetic for optimal long term
control
• All diabetics on insulin
• Brittle diabetics
• Ketosis and/or hypoglycemia prone diabetics
• Hypoglycemic awareness
• Whenever tight control is advocated e.g
pregnancy, infections, advanced complications
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46. What to do annually?
• Lipid profile
• Opthalmology check up with dilated pupil
• Blood urea/ creatinine
• Urine for protein/albumin/microalbuminuria
• ECG in patients above 40 years of age
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49. Metabolic Syndrome
Metabolic syndrome is defined by the National Cholesterol
Education Program - Adult Treatment Panel III as the presence
of at least three out of five key risk factors. The greater the
number of risk factors, the more at risk a patient is. The five
risk factors are:
1. Increased waist circumference (greater than 102
cm for men; greater than 88 cm for women)
2. Elevated levels of triglycerides (blood fats)
3. Low levels of HDL (good) cholesterol
4. Blood pressure (greater than or equal to 130/85 mmHg)
5. Impaired fasting glucose (insulin resistance)
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50. Metabolic Syndrome
WHO Criteria
Anyone who has diabetes or insulin resistance
and two of the following:
1. High waist-to-hip ratio;
2. High triglycerides or low HDL
cholesterol;
3. High blood pressure;
4. High urinary albumin excretion rate.
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51. Metabolic Syndrome
• Candidate definitions of MS were proposed by
modifying the NCEP ATPIII definition. These
modifications included the following: waist
circumference cutoffs as >90 cm in men and
>80 cm in women, BMI cutoff as >23 kg/m2, and
a measure of truncal subcutaneous fat
(subscapular skinfold thickness [SST] >18 mm).
Diabetes Care 28:398-403, 2005
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53. Metabolic Syndrome
"But there is no combination of risk factors that boosts a
person's cardiovascular risk beyond the sum of the parts,
or constitutes a separate disease,"
Ele Ferrannini, MD, President of the European Association for the Study of
Diabetes.
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Editor's Notes
Many patients are asymptomatic at diagnosis (Hyperglycemia is an incidental detection)
