Genetics of type 2 diabetes
- PMID: 20473152
- PMCID: PMC2953639
- DOI: 10.1097/MCO.0b013e32833a558d
Genetics of type 2 diabetes
Abstract
Purpose of review: To provide an overview of the genetics of type 2 diabetes in the context of recent progress in the understanding of the genetic architecture of the disease and its applicability to the pathogenesis of the disease as well as efforts to individualize therapy in type 2 diabetes. Efforts are underway to understand how these loci alter measurable physiologic processes in nondiabetic humans. However, it is important to understand the potential pitfalls in such studies and the limitations underlying measurement of insulin secretion and action using qualitative methodologies.
Recent findings: The availability of large population-based cohorts and the ease with which large numbers of common genetic variants can be genotyped has enabled the discovery of multiple loci and pathways associated with type 2 diabetes. Recent efforts examining quantitative traits such as fasting glucose concentrations have led to the discovery of other genes likely to be important in the development of diabetes.
Summary: The past 4 years have witnessed a significant increase in our understanding of genetic predisposition to type 2 diabetes. Hopefully more progress will be made in applying this knowledge to the pathophysiology of type 2 diabetes in the coming years.
Conflict of interest statement
Similar articles
-
Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond.Diabetologia. 2014 Aug;57(8):1528-41. doi: 10.1007/s00125-014-3270-4. Epub 2014 May 24. Diabetologia. 2014. PMID: 24859358 Review.
-
Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees.Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):379-384. doi: 10.1073/pnas.1705859115. Epub 2017 Dec 26. Proc Natl Acad Sci U S A. 2018. PMID: 29279374 Free PMC article.
-
Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity.Diabetes. 2014 Jun;63(6):2158-71. doi: 10.2337/db13-0949. Epub 2013 Dec 2. Diabetes. 2014. PMID: 24296717 Free PMC article. Review.
-
Recent progress in genetic and epigenetic research on type 2 diabetes.Exp Mol Med. 2016 Mar 11;48(3):e220. doi: 10.1038/emm.2016.7. Exp Mol Med. 2016. PMID: 26964836 Free PMC article. Review.
-
Quantitative trait loci near the insulin-degrading enzyme (IDE) gene contribute to variation in plasma insulin levels.Diabetes. 2004 Aug;53(8):2137-42. doi: 10.2337/diabetes.53.8.2137. Diabetes. 2004. PMID: 15277398
Cited by
-
Comprehensive analysis of endoplasmic reticulum stress-related mechanisms in type 2 diabetes mellitus.World J Diabetes. 2023 Jun 15;14(6):820-845. doi: 10.4239/wjd.v14.i6.820. World J Diabetes. 2023. PMID: 37383594 Free PMC article.
-
Effect of maternal PCOS and PCOS-like phenotype on the offspring's health.Mol Cell Endocrinol. 2016 Nov 5;435:29-39. doi: 10.1016/j.mce.2015.11.030. Epub 2015 Nov 27. Mol Cell Endocrinol. 2016. PMID: 26639019 Free PMC article. Review.
-
Diabetes-associated common genetic variation and its association with GLP-1 concentrations and response to exogenous GLP-1.Diabetes. 2012 May;61(5):1082-9. doi: 10.2337/db11-1732. Epub 2012 Mar 28. Diabetes. 2012. PMID: 22461567 Free PMC article.
-
Resistance to type 2 diabetes mellitus: a matter of hormesis?Nat Rev Endocrinol. 2011 Oct 25;8(3):183-92. doi: 10.1038/nrendo.2011.158. Nat Rev Endocrinol. 2011. PMID: 22024974 Review.
-
The islet circadian clock: entrainment mechanisms, function and role in glucose homeostasis.Diabetes Obes Metab. 2015 Sep;17 Suppl 1(0 1):115-22. doi: 10.1111/dom.12523. Diabetes Obes Metab. 2015. PMID: 26332976 Free PMC article. Review.
References
-
- Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects. Endocr Rev. 1998 Aug;19(4):477–90. - PubMed
-
- Bock G, Dalla Man C, Campioni M, Chittilapilly E, Basu R, Toffolo G, et al. Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance. Diabetes. 2006 Dec;55(12):3536–49. - PubMed
-
- Dinneen SF, Maldonado D, 3rd, Leibson CL, Klee GG, Li H, Melton LJ, 3rd, et al. Effects of changing diagnostic criteria on the risk of developing diabetes. Diabetes Care. 1998 Sep;21(9):1408–13. - PubMed
-
- Stolerman ES, Florez JC. Genomics of type 2 diabetes mellitus: implications for the clinician. Nature reviews. 2009 Aug;5(8):429–36. A comprehensive review of common genetic variation and association with type 2 diabetes. - PubMed
-
- Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010 Feb;42(2):105–16. This study identified 9 novel loci (out of a total of 16) which alter fasting glucose concentration. Five of these loci also confer risk of type 2 diabetes. - PMC - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous