Grant: Operating Grant

Background: Type 2 diabetes results in the yearly death of ~ 40,000 Canadians. Some obese subjects have higher risk to develop diabetes and my research will examine why. The risk for type 2 diabetes in obese subjects increases when the body is resistance to the action of insulin hormone (i.e. reduced insulin sensitivity) which leads to increased blood sugar and diabetes. I believe that insulin resistance is promoted by elevated numbers of the atherogenic particles that carries cholesterol in the blood (like LDL). Accordingly obese subjects with elevated particle numbers (termed hyperapoB) have higher risk for developing type 2 diabetes than those with normal particle numbers (termed normal apoB). Methods: I will recruit 96 obese subjects without diabetes or chronic disease (>45 years, 50%men, 50%postmenopausal women). Subjects with hyperapoB will be compared to subjects with normal apoB and equivalent cholesterol concentrations (48 subjects/ group) at 1) baseline and 2) following 6-months hypocaloric-diet intervention to reduce weight by 10%. Mechanisms examined to explain the differences in insulin sensitivity between the 2 groups will be; rate of dietary fat storage, inflammation in the blood and fat tissue, blood atherogenic particles profile and fat tissue genes that affect metabolism. Hypotheses: I hypothesize that compared to subjects with normal apoB, obese subjects with hyperapoB have 1) lower insulin sensitivity at baseline due to a slower rate of fat storage and higher inflammation, 2) greater increase in insulin sensitivity after weight loss due to a greater decrease in atherogenic particles' numbers and inflammation and a greater increase in the rate of fat storage. Significance: My study will identify obese subjects with hyperapoB as a high-risk group for the development of type 2 diabetes and will demonstrate that targeted treatment of these subjects may aid in reducing the risk of type 2 diabetes among the obese population.