Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology

The rapid rise in prevalence of type 2 diabetes mellitus (T2DM) has been driven by changes in environmental factors - primarily increased caloric intake and reduced energy expenditure - resulting in reduced whole body insulin sensitivity (often termed insulin resistance). Insulin resistance has been proposed to be a major driver of progression to T2DM. However, of 38 individual susceptibility loci for T2DM recently identified by genome wide association studies, by far the majority code for proteins involved in beta-cell function. In this review, we discuss the possible reasons for the paucity of insulin resistance genes and ask whether the new genetic susceptibility data should focus attention on beta-cell targets in the development of therapies for T2DM. (c) 2010 Elsevier Inc. All rights reserved.