Beta-cell preservation with thiazolidinediones.

Progressive beta-cell dysfunction and beta-cell failure are fundamental pathogenic features of type 2 diabetes. Ultimately, the development and continued progression of diabetes is a consequence of the failure of the beta-cell to overcome insulin resistance. Strategies that aim to prevent diabetes must, therefore, ultimately aim to stabilize the progressive decline of the beta-cell. Clinical study evidence from several sources now suggests that thiazolidinediones (TZDs) have profound effects on the beta-cell, such as improving insulin secretory capacity, preserving beta-cell mass and islet structure and protecting beta-cells from oxidative stress, as well as improving measures of beta-cell function, such as insulinogenic index and homeostasis model assessment of beta-cell function (HOMA-%B). Furthermore, intervention studies suggest that TZDs have the potential to delay, stabilize and possibly even prevent the onset on diabetes in high-risk individuals, and these effects appear to accompany improvements in beta-cell function. Here, we review the evidence, from in vitro studies to large intervention trials, for the effects of TZDs on beta-cell function and the consequences for glucose-lowering therapy.