2. Facts about Type II Diabetes Mellitus

3. “ Diabetes was long thought to be a kidney disease” (Greek & Arabic Methodology).

4. Diabetes Mellitus “ Thomas Willis (1621 - 1679), discovered the sweetness of urine, hence, the name Diabetes Mellitus arised”

5. “Mathew Dobson (1776), identified glycosuria”.

6. “Claude Bernard and Von Mering (1889), discovered in the same year that pancreatectomy causes diabetes”

7. “Fredrick Banting (1921), successfully, extracted insulin, gaining the Nobel prize for this great discovery”.

8. “Leonard Thompson (14 year old boy) & Elizabeth Hughes (aged 14 years), were the first patients to be treated with insulin in 1922.

9. Dear Mom,.. I look entirely different gaining every hour strength & weight....it is truly miraculous....I wish you could see the expression on there faces, they are so astounded in my unheard of progress.. Leonard, April, 1922

11. + It includes all the biochemical reactions that start in the cell after the absorption of food stuff. + Metabolism may be:  Anabolism: building up, needs energy.  Catabolism: breaking down, gives energy. METABOLISM

12. Important Terminology In Carbohydrate Metabolism Glycolysis: Glucose breakdown & utilization that occurs in cells. The breakdown of glycogen to glucose. Glycogenolysis:

13. Formation of glucose from fatty acids & amino acids (new glucose formation). Glycogenesis: Glycogen formation that occurs in liver & muscles for storage of carbohydrates (as glycogen). Gluconeogenesis:

14. í Organic substance composed of carbon, hydrogen & oxygen. í CHO are the first source of energy for the organism. CARBOHYDRATES

15. Simple sugarComplex sugar * Rapidly-absorbed CHO * Monosaccharides directly absorbed. * Glucose - Fructose - Galactose. * Slowly-absorbed CHO. * Disaccharides to polysaccharides need to be broken down to be absorbed as simple sugar. * Starch - Maltose. CLASSIFICATION OF CHO

16. Fate of Absorbed Glucose G Glycogenesis Glycolysis Muscle Cells 50 % G Glycolysis Lipogenesis G Glycogenesis Glycolysis Liver Cells 30 % Fat Cells 5 %

17. Regulation of Blood Glucose  Hormonal Regulation  Organic Regulation

18. Hormonal Regulation Blood Glucose Level < 110 mg/L Insulin Glucagon Growth Hormone Adrenaline Cortisol Hypoglycemic HormoneCounterregulatory Hormones

19. Insulin + The only Hypoglycemic Hormone + It is secreted by ß - cells of the islets of Langerhans of the pancreas. + Daily 20 - 50 units are secreted.

20. Insulin Synthesis PrePro Insulin Pro Insulin C peptideInsulin Split at position 61/62

22. INSULIN SECRETION GLUCOSE GK G-6-P PK PYRUVATES ATP Ca2+ DEPOLARIZATION + + + _ _ _ K + INSULIN Glu t 2 Blood Glucose

23. Insulin Secretion Curve Biphasic insulin response to a constant glucose stimulation (IVGTT - hyperglycemic Clamp) Insulin rate Time (min) Basal 460

24.  Early Peak  Late Phase Insulin secretion pattern

25. Insulin Secretion Pattern  Early peak: rapid.. Prestored insulin to prevent the marked increase of the blood glucose level.  Late phase: slow.. Newly fabricated insulin to normalise the blood glucose level.

26. Uptake Utilization Insulin Controls Blood Glucose metabolism by:

27. Insulin: Uptake of glucose  Stimulates glucose transporters to move to the cell surface. The process is passive in the kidney, liver and brain. Active in the other tissues.

28. Insulin: Glucose utilisation  Oxidation  Storage Liver & Muscles glycogen Adipocytes lipids

29. Glucose Oxidation (Glycolysis) InsulinGlucose T+ Glucose GK G - 6 - P PK Pyruvates Lactic Acid +2ATP PDH -0 2 Kreb’s Cycle 36ATP + CO 2 + H 2 O GK: Glucokinase PK:Pyruvate Kinase PDH:Pyruvate Dehydrogenase T:Insulin-dependent Transporter

30. How is Glucose Used in the Liver? InsulinGlucose T- Glucose GK G - 6 - P GSPK GlycogenPyruvates ATP GS:Glycogen Synthase T-:Non-insulin Dependent Transporter

31. How is Glucose Used in the Muscle Cells? InsulinGlucose T- Glucose HK G - 6 - P GS PK Glycogen Pyruvates ATP HK = Hexokinase

32. How is Glucose Used in the Adipocytes? InsulinGlucose T+ Glucose GK G - 6 - P PK Pyruvates ATP PDH GPDH Glycerol 3P + 3 Fatty Acids Triglycerides

33. What Happens Between Meals? glycogenolysis Glucose Gluconeogenesis I glycogenolysis Glucose Gluconeogenesis energy I I Lipolysis Fatty Acids + Glycerol

34. Organic regulation of the blood glucose I- Liver: Blood glucose glycogenolysis gluconeogenesis HGP glycogenesis glycolysis glucose

35. Organic regulation of the blood glucose II. Kidney  Normally no glucosuria  Above renal thresholdglucosuria (1.8g / L)

37. Definition + Diabetes Mellitus is a group of Metabolic Diseases characterized by Hyperglycemia resulting from defects in insulin secretion, insulin action, or both. American Diabetes Association

38. Diabetes Estimates and Projection

39. Classification of Diabetes Mellitus  Primary Diabetes Type 1insulin dependent diabetes Type 2non insulin dependent diabetes

40.  Secondary Diabetes Gestational diabetes Malnutrition related diabetes Diabetes resulting from:  Pancreatic disease  Hormonal diseases  Drug/chemical induced  Genetic syndromes  Secondary Diabetes Gestational diabetes Malnutrition related diabetes Diabetes resulting from:  Pancreatic disease  Hormonal diseases  Drug/chemical induced  Genetic syndromes Classification of Diabetes Mellitus

41. New Criteria: Diagnosis of D. Mellitus American Diabetes Association

42. Diabetes: Clinical Features  Symptoms: Polyuria Polydypsia=thrit Polyphagia=appetite Asthenia & Loss of weight  Signs: No specific signs may be signs of complications  Signs: No specific signs may be signs of complications

44. Key Organs of Diabetes Muscle Pancreas Liver Hyperglycemia in glucose storage in hepatic glucose production insulin secretion disorder

45. Peripheral Abnormalities Glycogenogenosis Glycolysis Gluconeogenesis Lipogenesis Lipolysis Glycogenogenesis Glycolysis Gluconeogenesis LiverFat tissues Muscles FFA Hyperglycaemia Glucose StorageGlucose production

46. Pathogenesis of diabetes: metabolic features Genetic predisposition Insulin resistance Insulin resistance Defective insulin secretion Hyperglycemia

47. Impaired Insulin Secretion

48. Causes of Impaired Insulin Secretion  Decrease in number of Beta cells by 40-50 % {In Insulin resistance states, the number is either normal or increased}

49. Amyloid deposits Amylin : amyloid material secreted by B cells Interferes with the recognition of the glucose signal Causes of Impaired Insulin Secretion

50.  Reduced activity of the glucokinase ATP production reduced inside B cells Closure of K channel decreases Entry of Calcium reduced release of Insulin reduced Causes of Impaired Insulin Secretion

51. Insulin Resistance

52. Types of Insulin Resistance  Receptor defect  Post Receptor defect

53. Types of Insulin Resistance  Receptor defect Decrease in the affinity Decrease in number (rare)

54.  Post receptor defect Glucose Transporter Intra cellular utilization Enzymatic activity Types of Insulin Resistance

55. Chronic hyperglycemia Insulin secretion disorder Insulin resistance Gluco-toxicity

57. Vascular complications  Microvascular complications  Macrovascular complications

58. Microvascular complications  Retinopathy  Nephropathy  Neuropathy

59. Macrovascular complications  CHD  CVD  PAD 10 years accelerated

60.  Thank You