In This Issue of Diabetes

Edited by Helaine E. Resnick, PhD, MPH

Mechanistically Oriented Clustering of Type 2 Diabetes Risk Alleles

Data in this issue of Diabetes indicate that many of the five dozen or so known type 2 diabetes risk variants cluster into just four groups that are based on mechanisms that underpin specific defects common in diabetes. The article by Dimas et al. (p. 2158) builds on findings from a smaller study in which 19 loci were examined in relation to a number of quantitative traits that are frequently associated with diabetes. The new study—which focuses on quantitative traits in nondiabetic people of European ancestry—is notable because of the breadth of data upon which the results are based, with basal measures available in up to 58,000 individuals and dynamic measures available from glucose or intravenous glucose tolerance challenges in up to 17,000 individuals. These data were used to examine 14 distinct phenotypes describing traits for a variety of defects that are known to increase diabetes risk, including fasting glucose and insulin, insulin sensitivity indices, Matsuda index, proinsulin, glucose uptake, and acute insulin response, among others. Of the 14 traits, 10 were based on sample sizes exceeding 10,000 individuals, and these principal traits were of particular interest in the new study. Initial cluster analyses showed that the phenotypes grouped together in ways that would be expected based on their relationships to diabetes physiology. Reclustering of these data with 37 of the established type 2 diabetes susceptibility loci generated four phenotype clusters. Each of these clusters contained specific susceptibility loci that were associated with the general defect in the cluster (e.g., insulin resistance, reduced insulin secretion and hyperglycemia, proinsulin processing, and β-cell function). The results of …

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This Article

  1. doi: 10.2337/db14-ti06 Diabetes vol. 63 no. 6 1821-1822
  1. Free via Open Access: OA