Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps

L.M. Hart; A.M.C. Bik-Simonis; G. Nijpels; T.W. van Haeften; S.A. Schäfer; J.J. Houwing-Duistermaat; D.I. Boomsma; M.J. Groenewoud; E. Reiling; E.C. van Hove; M. Diamant; M.H.H. Kramer; R.J. Heine; J.A. Maassen; K. Kirchhoff; F. Machicao; H.U. Häring; P.E. Slagboom; G. Willemsen; E.M.W. Eekhoff; E.J.C. de Geus; J.J.M. Dekker; A. Fritsche

doi:10.2337/db09-0736

Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps

L.M. Hart
, A.M.C. Bik-Simonis
, G. Nijpels
, T.W. van Haeften
, S.A. Schäfer
, J.J. Houwing-Duistermaat
, D.I. Boomsma
, M.J. Groenewoud
, E. Reiling
, E.C. van Hove
, M. Diamant
, M.H.H. Kramer
, R.J. Heine
, J.A. Maassen
, K. Kirchhoff
, F. Machicao
, H.U. Häring
, P.E. Slagboom
, G. Willemsen
, E.M.W. Eekhoff

E.J.C. de Geus, J.J.M. Dekker, A. Fritsche

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting. RESULTS - The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10

Original language	English
Pages (from-to)	287-292
Journal	Diabetes
Volume	59
Issue number	1
DOIs	https://doi.org/10.2337/db09-0736
Publication status	Published - 2010

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SDG 3 Good Health and Well-being

Cohort Studies

Netherlands Twin Register (NTR)

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10.2337/db09-0736

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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., ... Fritsche, A. (2010). Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps. Diabetes, 59(1), 287-292. https://doi.org/10.2337/db09-0736

@article{8296cfb4d6704ca8a3281dcdcd8b7fb3,

title = "Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps",

abstract = "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, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting. RESULTS - The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10",

author = "L.M. Hart and A.M.C. Bik-Simonis and G. Nijpels and \{van Haeften\}, T.W. and S.A. Sch{\"a}fer and J.J. Houwing-Duistermaat and D.I. Boomsma and M.J. Groenewoud and E. Reiling and \{van Hove\}, E.C. and M. Diamant and M.H.H. Kramer and R.J. Heine and J.A. Maassen and K. Kirchhoff and F. Machicao and H.U. H{\"a}ring and P.E. Slagboom and G. Willemsen and E.M.W. Eekhoff and \{de Geus\}, E.J.C. and J.J.M. Dekker and A. Fritsche",

year = "2010",

doi = "10.2337/db09-0736",

language = "English",

volume = "59",

pages = "287--292",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "1",

}

Hart, LM, Bik-Simonis, AMC, Nijpels, G, van Haeften, TW, Schäfer, SA, Houwing-Duistermaat, JJ, Boomsma, DI, Groenewoud, MJ, Reiling, E, van Hove, EC, Diamant, M, Kramer, MHH, Heine, RJ, Maassen, JA, Kirchhoff, K, Machicao, F, Häring, HU, Slagboom, PE, Willemsen, G, Eekhoff, EMW, de Geus, EJC , Dekker, JJM & Fritsche, A 2010, 'Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps', Diabetes, vol. 59, no. 1, pp. 287-292. https://doi.org/10.2337/db09-0736

TY - JOUR

T1 - Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps

AU - Hart, L.M.

AU - Bik-Simonis, A.M.C.

AU - Nijpels, G.

AU - van Haeften, T.W.

AU - Schäfer, S.A.

AU - Houwing-Duistermaat, J.J.

AU - Boomsma, D.I.

AU - Groenewoud, M.J.

AU - Reiling, E.

AU - van Hove, E.C.

AU - Diamant, M.

AU - Kramer, M.H.H.

AU - Heine, R.J.

AU - Maassen, J.A.

AU - Kirchhoff, K.

AU - Machicao, F.

AU - Häring, H.U.

AU - Slagboom, P.E.

AU - Willemsen, G.

AU - Eekhoff, E.M.W.

AU - de Geus, E.J.C.

AU - Dekker, J.J.M.

AU - Fritsche, A.

PY - 2010

Y1 - 2010

N2 - 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, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting. RESULTS - The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10

AB - 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, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting. RESULTS - The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10

U2 - 10.2337/db09-0736

DO - 10.2337/db09-0736

M3 - Article

SN - 0012-1797

VL - 59

SP - 287

EP - 292

JO - Diabetes

JF - Diabetes

IS - 1

ER -

Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps

Abstract

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