Prevention of Type 2 Diabetes
What is it really?
- From the Departments of Medicine, Obstetrics and Gynecology, and Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California
The current epidemic of type 2 diabetes in developed countries is occurring at three levels. First, more and more individuals are in positive calorie balance and accumulating fat in their bodies; they are becoming obese. Second, many of those obese individuals partition sufficient lipid in their livers and muscles and/or generate sufficient hormonal signals from fat cells to create insulin resistance. Third, pancreatic β-cells progressively fail in some individuals as they attempt to compensate for insulin resistance by increasing insulin output on a chronic basis. The β-cell failure tends to be slowly progressive over time and leads to progressively rising glucose levels that, when they become dangerous for eyes, kidneys, and nerves, define type 2 diabetes.
Prevention of type 2 diabetes requires arrest of the progressive β-cell dysfunction and stabilization of glucose concentrations at nondiabetic levels. Anything short of this arrest and stabilization will only delay the onset of type 2 diabetes. Theoretically, type 2 diabetes could be prevented or delayed by three types of interventions: 1) interventions that limit fat accumulation in the body (less obesity = less insulin resistance); 2) interventions that uncouple obesity from insulin resistance (less insulin resistance = less β-cell failure); and 3) interventions that directly preserve β-cell mass and/or function, despite the high secretory demands imposed by insulin resistance (better β-cell function = less diabetes).
Current efforts to prevent type 2 diabetes have used interventions that modify obesity and/or insulin resistance or that change glucose levels directly. The studies have generally not focused on the end points of stable glycemia and β-cell function. Rather, they have focused on reducing the fraction of patients with slightly elevated glucose levels (e.g., impaired glucose tolerance or “IGT”) who “cross the line” to diabetes, where the risk of microvascular complications begins. The studies have been conducted over periods …
