1. The inhibitory effect of recent type 2 diabetes risk loci on insulin secretion is modulated by insulin sensitivity.
- Author
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Haupt A, Guthoff M, Schäfer SA, Kirchhoff K, Machicao F, Gallwitz B, Staiger H, Stefan N, Fritsche A, and Häring HU
- Subjects
- Adult, Alleles, Body Composition, Body Mass Index, C-Peptide metabolism, Cohort Studies, Diabetes Mellitus, Type 2 epidemiology, Female, Gene Frequency, Genotype, Germany epidemiology, Glucose Tolerance Test, Humans, Insulin blood, Insulin Resistance genetics, Insulin-Secreting Cells physiology, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Diabetes Mellitus, Type 2 genetics, Insulin metabolism, Insulin Resistance physiology
- Abstract
Context/objective: Recently novel type 2 diabetes risk loci were identified and reported to associate with beta-cell dysfunction. We assessed whether the risk alleles in TCF7L2, CDKAL1, HHEX, SLC30A8, IGF2BP2, CDKN2A/2B, JAZF1, and WFS1 reduce insulin secretion in an additive manner and whether their impact is influenced by insulin sensitivity., Design/methods: We genotyped 1397 nondiabetic subjects for the aforementioned risk alleles and performed risk allele summation. Participants underwent an oral glucose tolerance test and in a subgroup also an iv glucose tolerance test with C-peptide and insulin measurements. In our cohort, only polymorphisms in SLC30A8, HHEX, TCF7L2, and CDKAL1 influenced insulin secretion. So we tested only these polymorphisms and, in a separate analysis, all above-mentioned polymorphisms., Results: We observed a 28% decline in insulin secretion with increment of risk alleles (P
- Published
- 2009
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