Genetics of Glucose Homeostasis Implications for Insulin Resistance and Metabolic Syndrome

Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 09/2012; 32(9):2091-6. DOI: 10.1161/ATVBAHA.112.255463
Source: PubMed


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.

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    • "Obesity, and more specifically the accretion of excess adipose tissue, is associated with elevated chronic systemic low-grade inflammation and increased risk of metabolic diseases, such as type 2 diabetes and cardiovascular disease (CVD) [2]. The pathogenesis of these conditions is attributable to a complex interaction between genetic, metabolic, environmental and behavioural factors, however the specific contribution of each of these determinants is not fully understood [3]. The composition and metabolic activity of microbial inhabitants of the human gut has recently been acknowledged as an environmental factor that may influence the development of obesity and associated metabolic diseases [4,5]. "
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