Facts about Type II Diabetes Mellitus

1. Facts about Type II Diabetes Mellitus

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

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

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

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

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

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

8. 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

9. medical background review

10. METABOLISM • 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.

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

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

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

14. CLASSIFICATION OF CHO Simple sugar Complex 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.

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

16. Regulation of Blood Glucose • Hormonal Regulation • Organic Regulation

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

18. 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.

19. Insulin Synthesis PrePro Insulin Split at position 61/62 Pro Insulin Insulin C peptide

21. Glu t2 Blood Glucose GLUCOSE GK G-6-P PK PYRUVATES B-Cell + K ATP + INSULIN _ _ + + _ DEPOLARIZATION Ca2+ INSULIN SECRETION

22. Insulin Secretion Curve Biphasic insulin response to a constant glucose stimulation (IVGTT - hyperglycemic Clamp) Insulin rate Basal Time (min) 4 60

23. Insulin secretion pattern • Early Peak • Late Phase

24. 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.

25. Insulin Controls Blood Glucose metabolism by: Uptake Utilization

26. 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.

27. Insulin: Glucose utilisation • Oxidation • Storage • Liver & Muscles glycogen • Adipocytes lipids

28. Glucose Oxidation (Glycolysis) Glucose Insulin T+ Glucose GK G - 6 - P PK Pyruvates Lactic Acid +2ATP PDH -02 GK: Glucokinase PK: Pyruvate Kinase PDH: Pyruvate Dehydrogenase T: Insulin-dependent Transporter 36ATP + CO2 + H2O Kreb’s Cycle

29. How is Glucose Used in the Liver? Glucose Insulin T- Glucose GK G - 6 - P GS PK Glycogen Pyruvates ATP GS: Glycogen Synthase T-: Non-insulin Dependent Transporter

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

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

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

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

34. Organic regulation of the blood glucose II. Kidney • Normally no glucosuria • Above renal threshold glucosuria (1.8g / L)

35. Diabetes Mellitus

36. 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

37. Diabetes Estimates and Projection

38. Classification of Diabetes Mellitus • Primary Diabetes • Type 1 insulin dependent diabetes • Type 2 non insulin dependent diabetes

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

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

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

42. METABOLIC ASPECTS

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

44. Peripheral Abnormalities Muscles Liver Fat tissues Gluconeogenesis Glycogenogenosis Glycolysis Glycolysis Lipogenesis Lipolysis Gluconeogenesis Glycogenogenesis FFA Glucose production Glucose Storage Hyperglycaemia

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

46. Impaired Insulin Secretion

47. 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}

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

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

50. Insulin Resistance