Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps
- Hart, L.M.
- Bik-Simonis, A.M.C.
- Nijpels, G.
- van Haeften, T.W.
- Schäfer, S.A.
- Houwing-Duistermaat, J.J.
- Boomsma, D.I.
- Groenewoud, M.J.
- Reiling, E.
- van Hove, E.C.
- Diamant, M.
- Kramer, M.H.H.
- Heine, R.J.
- Maassen, J.A.
- Kirchhoff, K.
- Machicao, F.
- Häring, H.U.
- Slagboom, P.E.
- Willemsen, G.
- Eekhoff, E.M.W.
- de Geus, E.J.C.
- Dekker, J.J.M.
- Fritsche, A.
DOIAbstract
OBJECTIVE - At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered β-cell function. In this study, we have investigated the combined effects of eight known β-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps. RESEARCH DESIGN AND METHODS - A total of 447 subjects originating from four independent studies in the Netherlands and Germany (256 with normal glucose tolerance [NGT]/ 191 with impaired glucose tolerance [IGT]) underwent a hyperglycemic clamp. A subset had an extended clamp with additional glucagon-like peptide (GLP)-1 and arginine (n = 224). We next genotyped single nucleotide polymorphisms in TCF7L2, KCNJ11, CDKAL1, IGF2BP2, HHE...
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