Genetics of type 2 diabetes: pathophysiologic and clinical relevance
Article first published online: 30 DEC 2010
© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 41, Issue 6, pages 679–692, June 2011
How to Cite
Herder, C. and Roden, M. (2011), Genetics of type 2 diabetes: pathophysiologic and clinical relevance. European Journal of Clinical Investigation, 41: 679–692. doi: 10.1111/j.1365-2362.2010.02454.x
- Issue published online: 3 MAY 2011
- Article first published online: 30 DEC 2010
- Received 30 September 2010; accepted 30 November 2010
- insulin action;
- insulin secretion;
- type 2 diabetes
Eur J Clin Invest 2011; 41 (6): 679–692
Background Recent genome-wide association studies enlarged our knowledge about the genetic background of type 2 diabetes.
Aims This review provides an overview of the role of these novel genetic findings for the pathophysiology, prediction and treatment of type 2 diabetes.
Results The genetic susceptibility to type 2 diabetes appears to be determined by many common variants in multiple gene loci with low effect sizes. Although at least 36 diabetes-associated genes were identified, only about 10% of the heritability of type 2 diabetes can be explained. Most of the discovered gene variants have been linked to beta-cell dysfunction rather than insulin resistance, which might challenge established thinking of type 2 diabetes as a predominant disorder of insulin action. Genetic data can lead to statistically significant, but not to clinically relevant contributions to risk prediction for type 2 diabetes. Nevertheless, preliminary evidence suggests interactions between genotypes and response to lifestyle changes or drug treatment.
Conclusions Future studies need to target the issue of hidden heritability and to detect the causal gene variants within the identified gene loci. Improved understanding of the genetic contribution to type 2 diabetes may then help addressing the questions whether genotyping is useful to predict individual diabetes risk, identifies individual responsiveness to preventive and therapeutic interventions or at least allows for breaking down type 2 diabetes into smaller, clinically meaningful subtypes.