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

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

4. Diabetes Mellitus “Diabetes is a dreadful affliction,---------”. “Diabetes is a dreadful affliction,---------”. Areteus of Cappadosia in 2 nd Century. Areteus of Cappadosia in 2 nd Century. It continues to be a sinister disease, if not taken care of. 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 YearsDiabetics(Million)1998135 2003170 2025300 Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2), 63-64

7. WHO ranks Pakistan 7 th on diabetes prevalance list- (The Nation ; English Daily- 15 th 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 higher prevalence of diabetes mellitus as compared to Western population Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP Vol.14(2) 63-64, WHO Estimates

8. Diabetes epidemiology in Pakistan YearsDiabetics(Million)19954.3 202514.5 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 ProvinceDiabetes Balochistan8.4% Kyber Pakhtun Khwa (KPK) 11.1% Sindh13.9% Punjab*10.9

10. Gender prevalence of DM Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2) 63-64 Diabetes Mellitus Males16.2% Females11.7% Impaired Glucose Tolerance Males8.2% Females14.3%

11. SURGE IN DIABETES MELLITUS Developing countries > 200% Developing countries > 200% Developed countries > 45% 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: 1.Increasing glucose transport into most insulin sensitive cells 2.Enhancing cellular utilization and storage of glucose 3.Enhancing utilization of amino acids 4.Promoting fat synthesis

14. INSULIN

16. Glucagon Is Dominant In The Fasting State  Glucagon prevents hypoglycemia.  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 Environment ? Viral infe..?? GeneticHLA-DR3/DR4 Severe Insulin deficiency ß cell Destruction Type 1 DM Autoimmune Insulinitis

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

20. Insulinitis Type 1 DM

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

24. Subcutaneous FatGluteal Fat Viceral Fat

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

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

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

29. I. CLASSIFICATION AND DIAGNOSIS OF DIABETES

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

31. Criteria for the Diagnosis of Diabetes HbA1C ≥6.5% OR Fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/l) OR Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT OR A random plasma glucose ≥200 mg/dl (11.1 mmol/l) ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

32. Prediabetes: IFG, IGT, Increased A1C Categories of increased risk for diabetes (Prediabetes)* FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG or 2-h plasma glucose in the 75-g OGTT 140-199 mg/dl (7.8-11.0 mmol/l): IGT or A1C 5.7-6.4% *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 Screening use plasma glucose fasting plasma glucose fasting and 2 hours after breakfast, and 2 hours after breakfast, if abnormal go for 50 gram oral glucose challenge test. if abnormal go for 50 gram oral glucose challenge test. In pregnant women previously known to have diabetes, and screening test abnormal go for 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