New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function

Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):371-7. doi: 10.1097/MCO.0b013e32830349a1.


Purpose of review: Over the past 18 months, the number of gene loci robustly associated with type 2 diabetes has risen from three to 18. In this study, we focus on explaining the genome-wide approach that has led to most of these discoveries and discuss some of the early insights the new gene loci have provided into the aetiology of type 2 diabetes.

Recent findings: Recent genome-wide association studies have provided an important resource for furthering our understanding of type 2 diabetes disease mechanisms. Genes previously unsuspected of playing a role in diabetes are now implicated in the disease process. These include genes in cell cycling control (CDKN2A/2B, CDKAL1), transcription factors (TCF7L2, HHEX), and ion channels (SLC30A8). These variants are all associated with insulin-secretory defects in the general population and show little if any relationship to insulin resistance. Two common variants (near or in FTO and MC4R) alter diabetes risk through a primary effect on obesity.

Summary: Recent genome-wide association studies show that there are now 18 gene loci associated with the risk of type 2 diabetes. Most of these T2D gene loci affect insulin secretion.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome, Human*
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology*


  • Insulin