1. Type 1 (IDDM) Type 2 (NIDDM)
Diabetes Mellitus
Type 1 (IDDM)
Type 2 (NIDDM)
20-Apr-19
Diabetes Mellitus

2. Diabetes Mellitus Group of metabolic disorders Hyperglycaemia due to
Sharing a common feature
Hyperglycaemia
Hyperglycaemia due to
Relative or absolute lack of insulin
Lack of insulin affect metabolism
Carbohydrate
Fats
Proteins
Water & electrolytes
20-Apr-19
Diabetes Mellitus

3. Diabetes Mellitus Hyperglycaemia in all cases is due
A functional deficiency of insulin action
Deficiency of insulin action
↓ in insulin secretion by B-cells
↓ response to insulin by target tissue
Insulin resistance
Or both
↑ in the counter regulatory hormones
Oppose the effects of insulin
20-Apr-19
Diabetes Mellitus

4. Diagnostic criteria
According to the National Diabetic Data group (NDDG) & WHO
Fasting plasma glucose  126 mg/dL (>7.0 mmol/L)
Symptoms of diabetes plus
Random plasma glucose  200 mg/dL ( 11.1 mmol/L)
Plasma glucose level  200 mg/dL ( 11.1 mmol/L) after
Oral dose of 75g of glucose (OGTT)
20-Apr-19
Diabetes Mellitus

5. Classification The two types traditionally classified
According to age at onset of DM
Juvenile DM
Maturity onset DM
According to therapy
Insulin dependent diabetes mellitus (IDDM)
Non-insulin dependent diabetes mellitus (NIDDM)
According to causation
Immune dependent diabetes mellitus (IDDM)
Non-immune dependent diabetes mellitus (NIDDM)
20-Apr-19
Diabetes Mellitus

6. Classification Type I diabetes mellitus
Insulin dependent diabetes mellitus (IDDM)
Caused by lack of Insulin
Immuno-dependent diabetes mellitus
20-Apr-19
Diabetes Mellitus

7. Classification Type II diabetes mellitus
Non Insulin dependent diabetes mellitus (NIDDM)
Caused by
Decreased sensitivity of target tissue to insulin
Insulin resistance
Non-immune dependent diabetes mellitus (NIDDM)
20-Apr-19
Diabetes Mellitus

8. Classification In both types of diabetes
Metabolism of main food stuff is altered
Efficient uptake and utilization of glucose
In most cells is prevented
↑ Blood glucose concentration
↑ glucose output by liver
↓ Insulin
↑ Glucagon
↑ utilization of fat and protein
20-Apr-19
Diabetes Mellitus

9. Type 1 Diabetes Mellitus
20-Apr-19
Diabetes Mellitus

10. Pathogenesis of Type 1 DM
Immuno-dependent diabetes mellitus
Results from severe lack of insulin
Due to destruction of B-cells
Auto-immune mechanism
20-Apr-19
Diabetes Mellitus

11. Pathogenesis of Type 1 DM
Factors that predispose to auto-immunity
Genetic susceptibility
Environmental factors
Viral infections
Measles, mumps, coxsackie virus B, rubella
20-Apr-19
Diabetes Mellitus

12. Pathogenesis of Type 1 DM
Onset could be
Early childhood (14 yrs)
Juvenile diabetes mellitus
May develop abruptly
Over a period of few days or weeks
Increase blood glucose concentration
Increased fat utilization
Depletion of protein
20-Apr-19
Diabetes Mellitus

13. Pathogenesis of Type 1 DM
Blood glucose concentration
↑ to very high levels
300 to 1200 mg/dL
20-Apr-19
Diabetes Mellitus

14. Type I Diabetes Mellitus
Consequences of elevated blood sugar levels
Glucosuria
Loss of glucose in urine
When blood glucose > 180 mg/dL
Cause osmotic diuresis
Polyuria
Na+ , K+ loss in urine
20-Apr-19
Diabetes Mellitus

15. Type I Diabetes Mellitus
For every gm of glucose excreted
4.1 kCal is lost
Hence there is ↑ in food intake
Polyphagia
Dehydration
High blood glucose concentration in ECF
↑ osmotic pressure in ECF
Cell dehydration
20-Apr-19
Diabetes Mellitus

16. Type I Diabetes Mellitus
Osmotic diuresis
Massive loss of fluid in urine
Dehydration of ECF, ICF
Excessive thirst
Polydypsia
Classic symptoms of diabetes
Polyuria
Polyphagia
20-Apr-19
Diabetes Mellitus

17. Type I Diabetes Mellitus
Chronic high glucose concentration
Cause tissue injury
Damage to blood vessels leads to
Inadequate blood supply to tissues
Increased risks of heart attack, stroke
Renal damage
Retinal damage
Ischaemia and gangrene of limbs
20-Apr-19
Diabetes Mellitus

18. Type I Diabetes Mellitus
Hypertension
Renal damage
Artherosclerosis
20-Apr-19
Diabetes Mellitus

19. Type I Diabetes Mellitus
Metabolic acidosis
Due to ↑ utilization of fats
↑ fat catabolism
↑ formation of ketone bodies
Acetoacetic acid, β-hydroxybutyric acid, acetone
Patient develops severe metabolic acidosis
Diabetic keto-acidosis (DKA)
Diabetic coma
20-Apr-19
Diabetes Mellitus

20. Type I Diabetes Mellitus
Protein metabolism in DM
DM causes depletion of body protein
Increase rate of protein breakdown
Release large quantity of AA
↑ rate of AA catabolism to release energy
AA converted into glucose
Gluconeogenesis
20-Apr-19
Diabetes Mellitus

21. Type I Diabetes Mellitus
Increased utilization of protein lead
Negative protein balance
Protein depletion
Wasting
Weight loss despite of
Excess food intake
20-Apr-19
Diabetes Mellitus

22. Type 2 DM
Adult onset DM
NIDDM
20-Apr-19
Diabetes Mellitus

23. Type 2 Diabetes Mellitus
Non-immune dependent diabetes mellitus
Comprise a heterogeneous group
Milder form of diabetes mellitus
Occurs predominantly in adults
Adult onset DM
20-Apr-19
Diabetes Mellitus

24. Type 2 DM More prevalent than type 1 DM
Has much stronger genetic predisposition
35% of 1st degree relative have DM or IGT
Interplay of genetic & environmental factors
20-Apr-19
Diabetes Mellitus

25. Type 2 DM Genetic factors Environmental factors
More important than in type 1 DM
However, autoimmune destruction of B-cells
Not involved in type 2 DM
Environmental factors
Sedentary lifestyle
Dietary habits
20-Apr-19
Diabetes Mellitus

26. Pathogenesis of Type 2 DM
More complex
Combination of
Insulin resistance
Relative insulin deficiency
Type 2 DM associated
Multiple metabolic abnormalities like type 2 DM
High levels of ketoacids usually not present
20-Apr-19
Diabetes Mellitus

27. Pathogenesis of Type 2 DM
Obesity, insulin resistance & metabolic syndrome
Precede development of type 2 DM
Insulin resistance appear to come first
↑ insulin secretion
↑ plasma insulin levels (hyperinsulinaemia)
To maintain BG levels
20-Apr-19
Diabetes Mellitus

28. Pathogenesis of type 2 DM
In susceptible individuals
B-cells are unable to sustain increased demands for insulin
There is ‘B-cell exhaustion’
BG rises to cause hyperglycaemia
20-Apr-19
Diabetes Mellitus

29. Pathogenesis of type 2 DM
In many instances type 2 DM May be controlled (in early stages) by
Dietary restrictions
Weight reduction
Drugs that increase insulin sensitivity
Metformins
Drugs that increase insulin release from B-cells
Sulfonylureas
20-Apr-19
Diabetes Mellitus

30. Insulin Resistance
Insulin resistance and impaired glucose tolerance (IGT)
Develop gradually
Begin with weight gain and obesity
Insulin resistance in obesity due to
? Few receptors in obese individuals
20-Apr-19
Diabetes Mellitus

31. Insulin Resistance Resistance appear to be caused by
Abnormality in the signaling pathway linking
Receptor activation
Metabolic effects of insulin
Impaired signaling related
Toxic effects of lipid accumulation
20-Apr-19
Diabetes Mellitus

32. Insulin Resistance Adipocytes (fat cells)
Adipokines (adipose cytokines)
Leptin, adiponectin, resistin
Biologically active substances
May contribute in the development of insulin resistance
20-Apr-19
Diabetes Mellitus

33. Insulin Resistance Other factors that can cause IR
Genetic abnormalities
Impair signaling pathway
Polycystic Ovary syndrome (PCOS)
↑ secretion of ovarian androgens
Insulin resistance
Excess formation of glucocorticoids
Cushing's syndrome
↓ sensitivity to metabolic effects of insulin
20-Apr-19
Diabetes Mellitus

34. Metabolic Syndrome
Insulin resistance is part of cluster of metabolic derangements
Metabolic syndrome
Syndrome X
Insulin resistance
Feature of metabolic syndrome
Hyperinsulinaemia
20-Apr-19
Diabetes Mellitus

35. Metabolic syndrome Features Obesity Fasting hyperglycaemia
Central or visceral obesity
Fasting hyperglycaemia
Lipid abnormalities (dyslipidaemia)
↑ blood TG, ↓HDL cholesterol
Hypertension
20-Apr-19
Diabetes Mellitus

36. Diagnosis Based on chemical tests of blood and urine Urinary glucose
Estimation of quantity of glucose lost in urine
Fasting blood glucose (FBG)
FBG in the morning 80 to 90 mg/dL
FBG > 110 mg/dL indicates diabetes
20-Apr-19
Diabetes Mellitus

37. Diagnosis Estimation of insulin levels
Type 1 DM
Insulin levels very low or undetected
Type 2 DM
High levels of insulin
Oral glucose tolerance test (OGTT
Unrestricted carbohydrate diet for 3 days
Fasted overnight (at least 8 hrs)
Rest before test
Plasma glucose measured 2 hrs after 75 g glucose load
20-Apr-19
Diabetes Mellitus

38. Glucose Tolerance Test (GTT)
Response to oral test doses of glucose
75 mg of glucose in 300 ml of water
In a normal individual
Resting fasting venous BG < 115mg/dL
20-Apr-19
Diabetes Mellitus

39. Glucose Tolerance Test (GTT)
The 2 hrs values
<140 mg/dL
No values >200mg/dL
Diabetes mellitus is present
2 hr value and one other value
>200 mg/dL
20-Apr-19
Diabetes Mellitus

40. Glucose Tolerance Test (GTT)
Impaired GTT
Values are above limits of normal
Below the diagnostic values for diabetes
Impaired GTT is due to
Reduced entry of glucose into cells
↓peripheral utilization
20-Apr-19
Diabetes Mellitus

41. Glucose Tolerance Test (GTT)
Glucose uptake by
Liver is also reduced
GIT is unaffected
Brain, RBCs normal
Renal absorption of glucose
Unaffected
Increased glucose output from liver
20-Apr-19
Diabetes Mellitus