1. Diabetes Mellitus Ibrahim Sales, Pharm.D. Assistant Professor of Clinical Pharmacy King Saud University isales@ksu.edu.sa

2. Learning Objectives Discuss the prevalence of diabetes mellitus (DM) globally and nationally Describe the pathophysiology of DM Identify diabetic complications to be considered in patients with diabetes Recognize the diagnostic criteria for DM Describe the benefits of controlling the DM risk factors

3. Worldwide Prevalence International Diabetes Federation. IDF Diabetes Atlas, 5th edn. Brussels, Belgium: International Diabetes Federation, 2011. http://www.idf.org/diabetesatlas http://www.idf.org/diabetesatlas

4. The Global Impact

5. 5

6. The Global Epidemic of Obesity

7. The Top Ranking Countries KSA UAE USA Egypt Kuwait

8. Current and Projected Prevalence 8

9. 9

10. Comparison of Type 1 and Type 2

11. 100 80 60 40 20 0 64 2 0 –2 –4 –6 –8 –10 –12 Years From Diagnosis  -cell Function (%) Reprinted with permission from Holman RR. Diabetes Res Clin Pract. 1998;40(suppl):S21 as modified from UKPDS Group. Diabetes. 1995;44:1249 UKPDS: Decline in  -Cell Function Prior to Diagnosis of Diabetes  -cell function Extrapolation to 100% function

12. N Engl J Med. 1988;318:1231-1239 Normal Glucose (mg/dL) Insulin (  U/mL) Normal Glucose and Insulin Profiles 100 200 300 400 0600100018001400020022000600 100018001400020022000600 Time of day 20 40 60 80 100 120 BLD BLD B=breakfast; L=lunch; D=dinner

13. N Engl J Med. 1988;318:1231-1239 Normal Type 2 on diet only Glucose (mg/dL) Insulin (  U/mL) Abnormal Glucose and Insulin Profiles in Type 2 Diabetes 100 200 300 400 0600100018001400020022000600 100018001400020022000600 Time of day 20 40 60 80 100 120 BLD BLD B=breakfast; L=lunch; D=dinner

14. Postprandial/Fasting Glucose Contributions to A1C % Contribution A1C Range (%) 0 20 40 60 80 100 FPG (Fasting Plasma Glucose) PPG (Postprandial Plasma Glucose) >10.2 70% 30% 9.3-10.2 60% 40% 8.5-9.2 55% 45% 7.3-8.4 50% <7.3 30% 70% Diabetes Care 2003; 26:881-885

15. Type 1 Diabetes Mellitus β-cell destruction Absolute deficiency in insulin Requires exogenous insulin

16. Type 2 Diabetes Mellitus

17. Microvascular Complications Retinopathy Leading cause of blindness Neuropathy Leading cause of non-traumatic lower extremity amputations Nephropathy Leading cause of end-stage renal disease (ESRD)

18. Macrovascular Complications

19. Reasons for Death in UKPDS 10-Year Follow-up

20. Chronic Disease Mortality Rate

21. Symptoms of Diabetes

22. Diagnosis American Diabetes Association (ADA) Guidelines 2014 A1C ≥ 6.5% FBG ≥ 126 mg/dL 2-hour post-prandial ≥ 200 mg/dL during an OGTT Random plasma glucose ≥ 200 mg/dL in a symptomatic patient Adapted from Diabetes Care 2014; 37(1): S14-S80

23. Case 1: Diagnosis of DM HA is a 32 y/o male presenting to the clinic for a follow-up visit. The last visit he had a fasting BG reading of 162 and today his HbA1C is 6.3%. Does this patient have DM? How can we confirm this?

24. Categories of Increased Risk for Diabetes (Prediabetes) CategoriesRanges Impaired Fasting Tolerance (IFT)FPG 100mg/dL (5.6mmol/L) to 125mg/dL (6.9mmol/L) Impaired Glucose Tolerance (IGT)2-h PG in the 75-g OGTT 140mg/dL (7.8 mmol/L) to 199mg/dL (11.0 mmol/L) A1C5.7-6.4%

25. Correlation of A1C with Average Glucose A1C (%)Mean plasma glucose mg/dLmmol/L 61267.0 71548.6 818310.2 921211.8 1024013.4 1126914.9 1229816.5 Adapted from Diabetes Care 2014; 37(1): S14-S80

26. Treatment Goals and Recommendations ADAAACE* A1C< 7%< 6.5% Preprandial70 – 13070 – 110 Post-prandial< 180< 140 Adapted from Diabetes Care 2014; 37(1): S14-S80 and Endocr Pract. 2011;17(2):1-53 *American Association of Clinical Endocrinologists

27. Glycemic Control in Type 2 DM

28. Treatment Goals and Recommendations Blood pressure< 140/80 mmHg LipidsRefer to hyperlipidemia guidelines. Foot inspectionQuarterly Monofilament Foot Exams Dilated Eye Exams Urine Protein Testing Annually VaccinationsFlu vaccine yearly Pneumonia vaccine ONCE (repeat once if > 65 y/o and previous was > 5 years prior) Adapted from Diabetes Care 2014; 37(1): S14-S80

29. Impact of a 1% Change in HbA1C

30. Benefits (Risk Reduction) from Each 1% Decrement in HbA1C

31. Intensive Treatment and Risk Reduction in UKPDS

32. Impact of HbA1C on the Risk of MI

33. Time to First Event

34. Lipid Intervention in Type 2 DM

35. Benefits of Blood Pressure Control

36. SBP and the Risk of Complications

37. The Impact of DBP on CV Outcomes

38. Antihypertensive Agents Needed to Achieve Target BP in DM

39. Calcium Channel Blockers in DM

40. Smoking and CV Risk

41. Type 2 DM

42. Insulin Resistance and Hyperglycemia

43. Natural History of Type 2 DM

44. Type 2 DM

45. DM Management in Primary Care

46. Treating Type 2 DM Insulin + Oral Agents Combination of Oral Agents Monotherapy Diet and Exercise A1C <7% This is a chain of failure!

47. Diabetes Mellitus Ibrahim Sales, Pharm.D. Assistant Professor of Clinical Pharmacy King Saud University isales@ksu.edu.sa