Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance

Alena Stancáková; Jussi Pihlajamäki; Johanna Kuusisto; Norbert Stefan; Andreas Fritsche; Hans Häring; Francesco Andreozzi; Elena Succurro; Giorgio Sesti; Trine Welløv Boesgaard; Torben Hansen; Oluf Pedersen; Per Anders Jansson; Ann Hammarstedt; Ulf Smith; Markku Laakso; EUGENE2 Consortium

doi:10.1210/jc.2007-2218

Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance

Alena Stancáková, Jussi Pihlajamäki, Johanna Kuusisto, Norbert Stefan, Andreas Fritsche, Hans Häring, Francesco Andreozzi, Elena Succurro, Giorgio Sesti, Trine Welløv Boesgaard, Torben Hansen, Oluf Pedersen, Per Anders Jansson, Ann Hammarstedt, Ulf Smith, Markku Laakso, EUGENE2 Consortium

Department of Biomedical Sciences

60 Citations (Scopus)

Abstract

CONTEXT: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes. OBJECTIVE: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes. DESIGN AND SETTINGS: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men. PARTICIPANTS: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 +/- 10 yr; body mass index 26.7 +/- 5.0 kg/m(2)) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects). Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2. MAIN OUTCOME MEASURES: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed. RESULTS: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. CONCLUSIONS: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	93
Issue number	5
Pages (from-to)	1924-30
Number of pages	6
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2007-2218
Publication status	Published - 2008

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1210/jc.2007-2218

Fingerprint

Dive into the research topics of 'Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance'. Together they form a unique fingerprint.

Cite this

Stancáková, A., Pihlajamäki, J., Kuusisto, J., Stefan, N., Fritsche, A., Häring, H., Andreozzi, F., Succurro, E., Sesti, G., Boesgaard, T. W., Hansen, T., Pedersen, O., Jansson, P. A., Hammarstedt, A., Smith, U., Laakso, M., & EUGENE2 Consortium (2008). Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. Journal of Clinical Endocrinology and Metabolism, 93(5), 1924-30. https://doi.org/10.1210/jc.2007-2218

Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. / Stancáková, Alena; Pihlajamäki, Jussi; Kuusisto, Johanna et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 5, 2008, p. 1924-30.

Research output: Contribution to journal › Journal article › Research › peer-review

Stancáková, A, Pihlajamäki, J, Kuusisto, J, Stefan, N, Fritsche, A, Häring, H, Andreozzi, F, Succurro, E, Sesti, G, Boesgaard, TW, Hansen, T, Pedersen, O, Jansson, PA, Hammarstedt, A, Smith, U, Laakso, M & EUGENE2 Consortium 2008, 'Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance', Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 5, pp. 1924-30. https://doi.org/10.1210/jc.2007-2218

Stancáková A, Pihlajamäki J, Kuusisto J, Stefan N, Fritsche A, Häring H et al. Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. Journal of Clinical Endocrinology and Metabolism. 2008;93(5):1924-30. doi: 10.1210/jc.2007-2218

Stancáková, Alena ; Pihlajamäki, Jussi ; Kuusisto, Johanna et al. / Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. In: Journal of Clinical Endocrinology and Metabolism. 2008 ; Vol. 93, No. 5. pp. 1924-30.

@article{18859f30ee1f11ddbf70000ea68e967b,

title = "Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance",

abstract = "CONTEXT: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes. OBJECTIVE: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes. DESIGN AND SETTINGS: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men. PARTICIPANTS: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 +/- 10 yr; body mass index 26.7 +/- 5.0 kg/m(2)) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects). Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2. MAIN OUTCOME MEASURES: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed. RESULTS: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. CONCLUSIONS: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.",

author = "Alena Stanc{\'a}kov{\'a} and Jussi Pihlajam{\"a}ki and Johanna Kuusisto and Norbert Stefan and Andreas Fritsche and Hans H{\"a}ring and Francesco Andreozzi and Elena Succurro and Giorgio Sesti and Boesgaard, {Trine Well{\o}v} and Torben Hansen and Oluf Pedersen and Jansson, {Per Anders} and Ann Hammarstedt and Ulf Smith and Markku Laakso and {EUGENE2 Consortium}",

note = "Keywords: Adult; Cyclin-Dependent Kinase 5; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Polymorphism, Single Nucleotide",

year = "2008",

doi = "10.1210/jc.2007-2218",

language = "English",

volume = "93",

pages = "1924--30",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance

AU - Stancáková, Alena

AU - Pihlajamäki, Jussi

AU - Kuusisto, Johanna

AU - Stefan, Norbert

AU - Fritsche, Andreas

AU - Häring, Hans

AU - Andreozzi, Francesco

AU - Succurro, Elena

AU - Sesti, Giorgio

AU - Boesgaard, Trine Welløv

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Jansson, Per Anders

AU - Hammarstedt, Ann

AU - Smith, Ulf

AU - Laakso, Markku

AU - EUGENE2 Consortium

N1 - Keywords: Adult; Cyclin-Dependent Kinase 5; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Polymorphism, Single Nucleotide

PY - 2008

Y1 - 2008

N2 - CONTEXT: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes. OBJECTIVE: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes. DESIGN AND SETTINGS: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men. PARTICIPANTS: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 +/- 10 yr; body mass index 26.7 +/- 5.0 kg/m(2)) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects). Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2. MAIN OUTCOME MEASURES: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed. RESULTS: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. CONCLUSIONS: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.

AB - CONTEXT: CDKAL1 is a recently discovered susceptibility gene for type 2 diabetes. OBJECTIVE: Our objective was to investigate the impact of rs7754840 of CDKAL1 on insulin secretion, insulin sensitivity, and risk of type 2 diabetes. DESIGN AND SETTINGS: Study 1 (the EUGENE2 study) was a cross-sectional study including subjects from five white populations in Europe (Denmark, Finland, Germany, Italy, and Sweden). Study 2 is an ongoing prospective study of Finnish men. PARTICIPANTS: In study 1, 846 nondiabetic offspring of type 2 diabetic patients (age 40 +/- 10 yr; body mass index 26.7 +/- 5.0 kg/m(2)) participated. In study 2, subjects included 3900 middle-aged men (533 type 2 diabetic and 3367 nondiabetic subjects). Interventions: Interventions included iv glucose-tolerance test (IVGTT), oral glucose-tolerance test (OGTT), and euglycemic-hyperinsulinemic clamp in study 1 and OGTT in study 2. MAIN OUTCOME MEASURES: Parameters of insulin secretion, insulin resistance, and glucose tolerance status were assessed. RESULTS: In study 1, carriers of the GC and CC genotypes of rs7754840 had 11 and 24% lower first-phase insulin release in an IVGTT compared with that in carriers of the GG genotype (P = 0.002). The C allele was also associated with higher glucose area under the curve in an OGTT (P = 0.016). In study 2, rs7754840 was significantly associated with type 2 diabetes (P = 0.022) and markers of impaired insulin release [insulinogenic index (IGI), P = 0.012] in 2405 men with normal glucose tolerance. CONCLUSIONS: rs7754840 of CDKAL1 was associated with markers of impaired insulin secretion in two independent studies. Furthermore, rs7754840 was associated with type 2 diabetes in Finnish men (study 2). Therefore, CDKAL1 is likely to increase the risk of type 2 diabetes by impairing insulin secretion.

U2 - 10.1210/jc.2007-2218

DO - 10.1210/jc.2007-2218

M3 - Journal article

C2 - 18285412

SN - 0021-972X

VL - 93

SP - 1924

EP - 1930

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 5

ER -