β-Cell preservation with thiazolidinediones

Progressive β-cell dysfunction and β-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 β-cell to overcome insulin resistance. Strategies that aim to prevent diabetes must, therefore, ultimately aim to stabilize the progressive decline of the β-cell. Clinical study evidence from several sources now suggests that thiazolidinediones (TZDs) have profound effects on the β-cell, such as improving insulin secretory capacity, preserving β-cell mass and islet structure and protecting β-cells from oxidative stress, as well as improving measures of β-cell function, such as insulinogenic index and homeostasis model assessment of β-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 β-cell function. Here, we review the evidence, from in vitro studies to large intervention trials, for the effects of TZDs on β-cell function and the consequences for glucose-lowering therapy.