Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Sep;32(9):2091-6.
doi: 10.1161/ATVBAHA.112.255463.

Genetics of glucose homeostasis: implications for insulin resistance and metabolic syndrome

Jill M Norris  1 , Stephen S Rich
Affiliations
Review

Genetics of glucose homeostasis: implications for insulin resistance and metabolic syndrome

Jill M Norris et al. Arterioscler Thromb Vasc Biol. 2012 Sep.

Abstract

This review summarizes the current understanding of the genetic basis of glucose homeostasis through genome-wide association scans and candidate gene studies of case-control and family-based designs. We highlight the implications of phenotype-direct (euglycemic clamp or frequently sampled intravenous glucose tolerance test) and indirect (fasting insulin and fasting glucose) measures on the determinants of insulin resistance and β-cell response that precede and contribute to the development of type 2 diabetes mellitus (T2DM) and the metabolic syndrome. Finally, we examine future approaches that may aid in understanding the biology of insulin resistance and T2DM. Over the past 2 decades, the prevalence of insulin resistance, the metabolic syndrome, and T2DM has increased. Ethnic differences in T2DM and insulin resistance are evident, with nonwhite populations having the greatest risk. There continue to be significant gaps in our knowledge regarding the metabolic, behavioral, and genetic determinants of these conditions. Understanding the genetic basis of glucose homeostasis, insulin resistance, and T2DM should provide insight on known and novel metabolic pathways that identify potential therapeutic targets and mechanisms for intervention.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Genetic and epidemiological basis of glucose homeostasis, insulin resistance, and the metabolic syndrome.
Figure 2
Figure 2
Changes of insulin sensitivity (Si) and acute-phase insulin response (AIR) from baseline (arrow base) to follow-up (arrow top) in populations stratified by baseline and follow-up glucose tolerance status. IGT indicates impaired glucose tolerance; DM, diabetes mellitus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104:787–794. - PMC - PubMed
    1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC, Jr International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–1645. - PubMed
    1. Groop L. Genetics of the metabolic syndrome. Br J Nutr. 2000;83 (Suppl 1):S39–S48. - PubMed
    1. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363:2339–2350. - PubMed
    1. Perry JR, Frayling TM. New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function. Curr Opin Clin Nutr Metab Care. 2008;11:371–377. - PubMed

Publication types

MeSH terms