1. Type 2 Diabetes – A Global Epidemic Arya M Sharma, MD, FRCP(C) Professor of Medicine Research Chair for Obesity Research & Management University of Alberta Medical Director Edmonton Weight Wise Program Edmonton, AB, Canada www.drsharma.ca

7. An estimated 285 million people worldwide are affected by diabetes. With a further 7 million people developing diabetes each year, this number is expected to hit 438 million by 2030.

8. More than 3 million Canadians have diabetes and this number is expected to reach 3.7 million by 2020.

9. Diabetes is a contributing factor in the deaths of approximately 41,500 Canadians each year.

10. 50% of Canadians diagnosed with type 2 diabetes do not achieve the CDA Guidelines target level of blood glucose. DICE Study

11. Abdominal obesity increases the risk of developing type 2 diabetes <7171–75.976–8181.1–8686.1–9191.1–96.3>96.3 24 20 16 12 8 4 0 Relative risk Waist circumference (cm) Carey V, 1997

12. Conventional treatment (n = 411)* UKPDS 34. Lancet 1998:352:854; Kahn SE, et al. N Engl J Med 2006;355:2427 The Double-Edged Sword: Weight Gain With Diabetes Treatment *Diet initially then sulphonylureas, insulin, and/or metformin if FPG > 15 mmol/L FPG = fasting plasma glucose Change in weight (kg) Years from randomization 0 1 5 036912 8 7 6 4 3 2 Insulin (n = 409) Glyburide (n = 277) Metformin (n = 342) UKPDS Weight gain up to 8 kg over 12 years

13. Depression Pseudotumor cerebri Obstructive sleep apnea Coronary artery disease Heart failure Fatty liver Thrombosis Osteoarthritis Intertrigo Incontinence Gallbladder disease Infertility GE-Reflux disease Hypertension Diabetes Gout Cancer Sharma 2006 Health Consequences of Obesity

14. Obesity Treatment Pyramid Diet Physical Activity Lifestyle Modification Pharmacotherapy Surgery

15. Placebo Metformin Lifestyle Diabetes Prevention Study Mean Weight Change The DPP Research Group, NEJM 346:393-403, 2002

16. Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Metformin, p<0.001 vs. Placebo) Diabetes Prevention Study Incidence of Diabetes Risk reduction 31% by metformin 58% by lifestyle The DPP Research Group, NEJM 346:393-403, 2002

19. The Dilemma Kg decades

20. Weight Curves in Obese and Never-Obese Rats MacLean PS et al. Am J Physiol 2004

21. Isn’t Obesity Simple? Energy In Energy Out +/- Energy Regulation is Complex! Environmental Determinants Environmental Determinants Sharma AM 2007 Genetics

22. Central Control of Energy Metabolism

23. Variability in Weight Gain Response to Overfeeding (+1000 KCal/day) in Healthy Sedentary Volunteers  men  women Harris AM et al. Obesity 2006;14:690-695

24. Principal Sites of Synthesis of GI Peptides Implicated in the Regulation of Food Intake Cummings & Overduin J Clin Invest. 2007;117:13

25. Phases of Obesity Treatment Phase I (Weight Loss) 3-6 months Phase II (Weight-Loss Maintenance) Indefinitely When you stop treatment, the disease comes back! Weight

26. Treatment Success Change in Weight Years Lifestyle (LS) ~ 3-5% LS+Surgery ~ 20-30% LS+Pharmacotherapy ~ 5-15%

27. Randomized Controlled Trial of Weight-Loss Maintenance Svetky LP et al., JAMA 2008;299:1139

28. STORM Mean bodyweight changes during weight loss and weight maintenance phases over 2 years 104 102 100 98 96 94 92 90 88 012246810141618202224 Month Bodyweight (kg) Control Sibutramine Weight loss Weight maintenance Same diet and exercise for both sibutramine and control James WPT, Lancet 2001

29. Bariatric Surgery Reduces Mortality in Swedish Obese Subjects (n=2010 vs. 2037) Sjostrom L et al. NEJM 2007;357:741-52 30% Reduction in All Cause Mortality

30. Bariatric Surgery Effect on Cardiovascular Risk A Systematic Review and Meta-Analysis of 22,090 Patients % resolved 62% 70% 77% 86% Hypertension Dyslipidemia Diabetes Sleepapnea Buchwald H, et al. JAMA 2004;292:1724

31. , 2004

32. Key Points  We currently have a “diabesity” epidemic in Canada  Conventional treatment of “diabesity” is limited and expensive  New thinking is required to better manage this epidemic

33. My Obesity Blog: www.drsharma.ca