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Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies

descriptionPublicationkeyboard_double_arrow_right Article 10 Dec 2008 English Publisher:Springer Science and Business Media LLCJournal:Acta Diabetologica, volume 46, pages 217-226 (issn: 0940-5429, eissn: 1432-5233,

Authors: Tuomo Rankinen; Stephanie-May Ruchat; S. John Weisnagel; Ruth J. F. Loos; Cathy E. Elks; Marie-Claude Vohl; Claude Bouchard; +1 Authors

doi: 10.1007/s00592-008-0080-5

pmid: 19082521

Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies

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Abstract

Several single nucleotide polymorphisms (SNPs) for type 2 diabetes mellitus (T2DM) risk have been identified by genome wide association studies (GWAS). The objective of the present study was to investigate the impact of these SNPs on T2DM intermediate phenotypes in order to clarify the physiological mechanisms through which they exert their effects on disease etiology. We analysed 23 SNPs in 9 T2DM genes (CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8, TCF2, TCF7L2 and WFS1) in a maximum of 712 men and women from the Quebec Family Study. The participants underwent a 75 g oral glucose tolerance test (OGTT) and were measured for glucose, insulin and C-peptide levels. Indices of insulin sensitivity and insulin secretion were derived from fasting and OGTT measurements. We confirmed the significant associations of variants in CDKAL1, CDKN2B, HHEX/IDE, KCNJ11 and TCF7L2 with insulin secretion and also found associations of some of these variants with insulin sensitivity and glucose tolerance. IGF2BP2 and SLC30A8 SNPs were not associated with insulin secretion but were with insulin sensitivity and glucose tolerance (0.002

Related Organizations

Université Laval
Canada
Pennington Biomedical Research Center
United States
MRC Integrative Epidemiology Unit
United Kingdom

Keywords

Adult, Blood Glucose, Male, Quebec, Glucose Tolerance Test, Middle Aged, Polymorphism, Single Nucleotide, Diabetes Mellitus, Type 2, Gene Frequency, Risk Factors, Insulin-Secreting Cells, Insulin Secretion, Humans, Insulin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study

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