Diabetes Mellitus

1. Diabetes Mellitus • Global and national prevalence of diabetes • Types of diabetes • Pathogenesis of diabetes • Classification and criteria for lab diagnosis of diabetes • Lab investigations for a patient of diabetes • MCQ’s

3. The Miracle of Insulin February 15, 1923 Patient J.L., December 15, 1922

4. Diabetes Mellitus • “Diabetes is a dreadful affliction,---------”. • Areteus of Cappadosia in 2nd Century. • It continues to be a sinister disease, if not taken care of. Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2), 63-64

6. Diabetes a global epidemic Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2), 63-64

7. WHO Estimates WHO ranks Pakistan 7th on diabetes prevalance list- (The Nation ; English Daily- 15th Nov 2008) Pakistan ranked eighth in the world for Diabetes Mellitus (1995), • After India, China, USA, Russia, Japan, Brazil, and Indonesia.Asian and other developing countries have higherprevalence of diabetes mellitus as compared to Western population Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP Vol.14(2) 63-64 ,

8. Diabetes epidemiology in Pakistan Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2) 63-64

9. The provincial prevalence of diabetes mellitus- Pakistan Basit .A et al, Frequency of Chronic Complications of type II Diabetes JCPSP 2004 Vol.14 (2): 79-83 *Shera AS et a; Pak national diabetes survey, J of Primary Care Diab, 2010 Vol 4 79-83

10. Gender prevalence of DM Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2) 63-64

11. SURGE IN DIABETES MELLITUS • Developing countries> 200% • Developed countries > 45% • Type 2 diabetes, will be 90% of all cases. Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2) 63-64

12. Normal Pancreatic Islets: ß cells Glucagon cells

13. Insulin Promotes Anabolism Insulin lowers plasma glucose by: • Increasing glucose transport into most insulin sensitive cells • Enhancing cellular utilization and storage of glucose • Enhancing utilization of amino acids • Promoting fat synthesis

14. INSULIN

16. Glucagon Is Dominant In The Fasting State • Glucagon preventshypoglycemia. • Glucagon is secreted when plasma glucose levels fall below 100 mg/dL. • The liver is the primary target of glucagon. • Glucagon stimulates glycogenolysis and gluconeogenesis to increase glucose output by the liver. • Glucagon release is also stimulated by plasma amino acids.

17. GLUCAGON

18. Pathogenesis of Type 1DM Genetic HLA-DR3/DR4 Environment ? Viral infe..?? Autoimmune Insulinitis ß cell Destruction Severe Insulin deficiency Type 1 DM

19. Natural History Of “Pre”–Type 1 Diabetes Putative trigger -Cell mass 100% Cellular autoimmunity Circulating autoantibodies (ICA, GAD65) Loss of first-phase insulin response (IVGTT) Clinical onset— only 10% of-cells remain Glucose intolerance (OGTT) Genetic predisposition Insulitis-Cell injury “Pre”-diabetes Diabetes Time Eisenbarth GS. N Engl J Med. 1986;314:1360-1368 14

20. Insulinitis Type 1 DM

21. Pathogenesis of Type 2 DM ß cell defect Genetic Environment Obesity ??? Abnormal Secretion Insulin resistance Relative Insulin Def. ß cell exhaustion IDDM Type 2 DM

24. Subcutaneous Fat Gluteal Fat Viceral Fat

25. Islets in Type 2 Diabetes: • Loss of ß cells • Amyloid deposits • Hyalinization

26. Natural History of Type 2 Diabetes Impaired glucose tolerance Undiagnosed diabetes Known diabetes Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Microvascular complications Macrovascular complications Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789 17

27. Age: < 40 Years Duration: Weeks Ketonuria: Common Insulin- Dependent Autoantibody: Yes Family History: No Insulin levels: very low Islets: Insulinitis Complications: Acute & Metabolic > 40 Years Months to years Rare Independent * No Yes Normal or high * Normal / Exhaustion Complications Late and vascular. Type-1 Type-2

29. I. CLASSIFICATION AND DIAGNOSIS OF DIABETES

30. Classification of Diabetes • Type 1 diabetes • β-cell destruction • Type 2 diabetes • Progressive insulin secreting defect • Other specific types of diabetes • Genetic defects in β-cell function, insulin action • Diseases of the exocrine pancreas • Drug- or chemical-induced • Gestational diabetes mellitus ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S12.

31. Criteria for the Diagnosis of Diabetes ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

32. Prediabetes: IFG, IGT, Increased A1C *For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range. ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.

33. Recommendations:Detection and Diagnosis of GDM Screening use plasma glucose fasting and 2 hours after breakfast, if abnormal go for 50 gram oral glucose challenge test. In pregnant women previously known to have diabetes, and screening test abnormal go for confirmatory test for diagnosis of GDM at 24-28 weeks gestation, using a 100 gram glucose- OGTT

34. Other investigations: • Serum Urea. • Serum Creatinine • Serum Lipid profile: cholesterol; triglyceride; LDL-C; HDL-C. • Serum sodium, potassium, • 24 hour urine for: protein; creatinine clearance; microalbumin; • Spot urine for microalbumin • Spot urine for albumin creatinine ratio- ACR

35. Other investigations and evaluations: • Blood complete picture • Urine routine examination: glucose; protein/, albumin, WBC, sp gravity. • Urine for ketone bodies • Arterial blood gases-ABG’s • Ultra sound liver- Fatty liver • Fundoscopy- for diabetic retinopathy; • Routine eye exam: diabetic cataract • Blood pressure measurement • Examination of feet- ulcer; poor sensations/neuropathy

36. Thank you