1. T2DM MANAGEMENT DENTAL COURSE 2010 2011 Mohamed AlMaatouq, MD King Khalid University Hospital King Saud University

2. OBJECTIVES 1.GENESIS OF DM 2.DM I 3.DM IIINSULIN RESISTANCE 4.DM MANAGEMENT 5.Rx GUIDELINES (IDF) 6.NOTES 7.CONCLUSIONS

3. U.S. Diabetes Prevalence —Diabetes kills 1 American every 3 minutes —New case diagnosed every 40 seconds —More deaths than AIDS and breast cancer combined —Average life expectancy: 15 years less than non- diabetes population —Afflicts over 177 million people worldwide —300 million afflicted by 2025 18 Million

4. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin Diabetes Prevention Program Research Group ABSTRACT Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin. Volume 346:393-403 February 7, 2002 Number 6

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8. Novo Nordisk devices in diabetes care First pen (NovoPen 1) launched in 1985 Committed to developing one new insulin administration system per year.

9. Lilly Insulin Pens

10. Novo FlexPen ® l 3-mL prefilled disposable pen offers precise dosing

11. PARADIGM PUMP Paradigm. Simple. Easy.

12. CGMS

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18. AND MANY OTHER THINGS

19. Genetic Acquired Obesity Age Pathogenesis of type 2 Diabetes Mellitus Insulin resistance

26. Slide Source: Lipids Online www.lipidsonline.org

27. DIABETES MELLITUS (DM II) Essentials of Good Care: 1.Identify patients at risk 2.Establish accurate diagnosis and classifications. 3.Re-evaluate previously diagnosed patients. 4.Evaluate risk factors for macrovascular disease and other complications. 5. Plan appropriate therapy. 6.Monitor patients regularly. 7. Attempt to prevent complications. 8. Diagnose and treat complications early.

28. MANAGEMENT OF DM II 1.Reduce MACROVASCULAR disease risk. a.stop smoking b.aspirin c.lipids d.ACE I 2.B P control 3. Evaluate for Chronic DM Complications. 4.BS control 5.Others

29. Insulin Resistance Syndrome DyslipidemiaHypertension Central obesity Hyperglycemia Endothelial dysfunction/ microalbuminuria Cardiovascular Disease InflammationHypofibrinolysis Insulin Resistance

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31. Treating type 2 diabetes means treating hyperglycaemia and the dysmetabolic syndrome Good glycaemic control Insulin resistance, obesity, hyperinsulinaemia, hypertension, dyslipidaemia, atherosclerosis, procoagulant state Dysmetabolic syndrome Microvascular and macrovascular complications NEED TO TREAT

32. The Metabolic Syndrome: a network of atherogenic factors Atherosclerosis McFarlane S, et al. J Clin Endocrinol Metab 2001; 86:713–718. Genetic factors Environmental factors Insulin Resistance Hyperglycemia/IGT Dyslipidemia Hypertension Endothelial dysfunction/ Microalbuminuria Hypofibrinolysis Inflammation

43. MANAGEMENT OF DM II 1.Reduce MACROVASCULAR disease risk. a.stop smoking b.aspirin c.lipids d.ACE I 2.B P control 3. Evaluate for Chronic DM Complications. 4.BS control 5.Others

56. MANAGEMENT OF DM II 1.Reduce MACROVASCULAR disease risk. a.stop smoking b.aspirin c.lipids d.ACE I 2.B P control 3. Evaluate for Chronic DM Complications. 4.BS control 5.Others

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61. EVERY 1% reduction in HBA 1C REDUCED RISK* 1% Deaths from diabetes Heart attacks Microvascular complications Peripheral vascular disorders UKPDS 35. BMJ 2000; 321: 405-12 Lessons from UKPDS: Better control means fewer complications -37% -43% *p<0.0001 -14% -21%

62. ADA. Diabetes Care 2002; 25:S33  S49. Current ADA treatment targets HbA 1c < 7% Blood pressure < 130/< 80 mmHg LDL cholesterol < 100 mg/dl (2.6 mmol/l) HDL cholesterol Men> 45 mg/dl (1.15 mmol/l) Women > 55 mg/dl (1.40 mmol/l) Triglycerides < 150 mg/dl (1.7 mmol/l)

63. The evolution of management guidelines Studies including UKPDS have highlighted the importance of glycemic control in reducing complications New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects of the condition Current guidelines therefore include targets for glycemic control lipid levels blood pressure

64. Lifestyle intervention Represents the first step in treating type 2 diabetes Lifestyle management reduced progression to diabetes by 58% in patients at risk of diabetes: Finnish Diabetes Prevention Study 1 Diabetes Prevention Program 2 However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis 1. Tuomilehto J, et al for the Finnish Diabetes Prevention Study Group. N Engl J Med 2001; 344:1343–1350. 2. Bailey CJ. Br J Diabetes Vasc Dis 2001; 1:62–64.

69. Glucose Insulin I I I I I I I I G G G G G G G G I G G G Adipose tissue Liver Pancreas Muscle Gut I G Carbohydrate Stomach  -glucosidase inhibitors Sulfonylureas and meglitinides Biguanides Adapted from Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl 1):S32–S40. Thiazolidinediones Primary sites of action of oral anti-diabetic agents

70. The ideal profile for an oral anti-diabetic agent Targets underlying causes of type 2 diabetes: insulin resistance  -cell dysfunction Effective/sustained glycemic control in monotherapy and combination Good safety and tolerability profile Reduces microvascular/macrovascular complications Delays/reverses disease progression

73. Diet/ exercise + Oral monotherapy Diet/exercise + Oral combination Diet/exercise + Insulin Early aggressive combination therapy Stepwise treatment Diet/exercise + Oral +/- insulin New treatment paradigms for type 2 diabetes

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76. DIABETES MELLITUS (DM II) Essentials of Good Care: 1.Identify patients at risk 2.Establish accurate diagnosis and classifications. 3.Re-evaluate previously diagnosed patients. 4.Evaluate risk factors for macrovascular disease and other complications. 5. Plan appropriate therapy. 6.Monitor patients regularly. 7. Attempt to prevent complications. 8. Diagnose and treat complications early.

77. MANAGEMENT OF DM II 1.Reduce MACROVASCULAR disease risk. a.stop smoking b.aspirin c.lipids d.ACE I 2.B P control 3. Evaluate for Chronic DM Complications. 4.BS control 5.Others

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80. MANAGEMENT OF DM II 1.Reduce MACROVASCULAR disease risk. a.stop smoking b.aspirin c.lipids d.ACE I 2.B P control 3.Evaluate for Chronic DM Complications. 4.BS control 5.Others

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82. CONCLUSIONS

83. OBJECTIVES 1.GENESIS OF DM 2.DM I 3.DM IIINSULIN RESISTANCE 4.DM MANAGEMENT 5.Rx GUIDELINES (IDF) 6.NOTES 7.CONCLUSIONS