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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
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Stancakova, A. (author)
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Pihlajamaki, J. (author)
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Kuusisto, J. (author)
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Stefan, N. (author)
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Fritsche, A. (author)
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Haring, H. (author)
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Andreozzi, F. (author)
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Succurro, E. (author)
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Sesti, G. (author)
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Boesgaard, T. W. (author)
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Hansen, T. (author)
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Pedersen, O. (author)
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- Jansson, Per-Anders, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Hammarstedt, Ann, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Smith, Ulf, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Laakso, M. (author)
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(creator_code:org_t)
- The Endocrine Society, 2008
- 2008
- English.
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In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:5, s. 1924-30
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Adult
- Cyclin-Dependent Kinase 5/*genetics
- Diabetes Mellitus
- Type 2/*genetics
- Female
- *Glucose Tolerance Test
- Humans
- Insulin/*secretion
- Insulin Resistance
- Male
- Middle Aged
- *Polymorphism
- Single Nucleotide
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Stancakova, A.
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Pihlajamaki, J.
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Kuusisto, J.
-
Stefan, N.
-
Fritsche, A.
-
Haring, H.
-
show more...
-
Andreozzi, F.
-
Succurro, E.
-
Sesti, G.
-
Boesgaard, T. W.
-
Hansen, T.
-
Pedersen, O.
-
Jansson, Per-And ...
-
Hammarstedt, Ann ...
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Smith, Ulf, 1943
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Laakso, M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Journal of Clini ...
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University of Gothenburg
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Karolinska Institutet