Type 2 Diabetes

Abstract

This is the first of a series of articles based on presentations at the American Diabetes Association (ADA) 70th Scientific Sessions held on 25–29 June 2010 in Orlando, Florida, pertaining to thiazolidinedione(s) (TZD) and to approaches to insulin treatment for type 2 diabetes. At a symposium on the role of TZD, Thomas Buchanan (Los Angeles, CA) discussed the β-cell benefits of TZD and their action to slow the progression of diabetes. Clinically, the agents increase body fat, acting to increase appetite, but making fat “behave better” and leading to a reduction in insulin resistance and improved glycemia. TZDs alter circulating lipids, lower blood pressure, reduce coronary artery restenosis after percutaneous intervention, and decrease ultrasonographic progression of carotid and coronary artery disease but increase the risk of distal extremity (and perhaps other skeletal) fracture and of congestive heart failure. They may alter the risk of acute occlusive events. To set the stage for understanding the TZD effect on β-cell function, Buchanan reviewed the hyperbolic relationship between insulin sensitivity and insulin secretion. The product of the two parameters, the disposition index, decreases as diabetes develops. Cross-sectional data suggest that, as the fasting glucose increases from under 100 to 100–140 and again from 140 to 180 mg/dL, there is particularly great deterioration in β-cell function, with lesser deterioration as glucose levels increase further (1). Buchanan reviewed his studies, comparing those who had developed diabetes with those who had not after having had gestational diabetes. There was a nonlinear relationship between reduction in β-cell function and elevations in glucose levels, with greater reduction leading to the development of diabetes (2). Although he pointed out that higher blood glucose, lesser β-cell function, and worse degrees of insulin resistance “doesn't actually tell you why they develop diabetes,” Buchanan reviewed further analysis showing weight gain to …