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Fritsche, L. ; Sarief, M. ; Wagner, R. ; Stefan, N. ; Lehmann, R. ; Häring, H.-U. ; Grallert, H. ; Fritsche, A. ; Lechner, A.

Genetic variation in TCF7L2 rs7903146 and history of GDM negatively and independently impact on diabetes-associated metabolic traits.

Diabetes Res. Clin. Pract. 146, 251-257 (2018)
Postprint DOI PMC
Open Access Green
Aims: Gestational diabetes (GDM) is recognized as a major risk factor for the development of type 2 diabetes (T2DM) later in life. Risk allele carriers at TCF7L2 rs7903146 have increased susceptibility for both GDM and T2DM. We hypothesized that carrying TCF7L2 risk alleles would further aggravate the negative impact of a positive history for GDM on metabolic traits related to T2DM later in life.Methods: 210 women with a confirmed history of gestational diabetes and 810 controls without evidence for GDM underwent standardized 75 g oral glucose tolerance tests (OGTT). Liver fat was quantified in a subset of subjects (n = 444) using magnetic resonance spectroscopy.Results: 504 women were homozygous or heterozygous risk allele carriers. The risk allele carriers had a higher risk for GDM (p = 0.0076, OR 1.52, 95% CI 1.11-2.06). Multivariable regression analysis demonstrated that both a history of GDM, or carrying a TCF7L2 risk allele resulted in lower insulin secretion, impaired proinsulin processing and higher fasting and 2-hour glucose levels. Liver fat content was not associated with either a history of GDM or a TCF7L2 risk genotype. There was no significant interaction (all p > 0.05) between history of GDM and TCF7L2 risk alleles on all diabetes-associated metabolic traits tested.Conclusion: The TCF7L2 rs7903146 polymorphism is a risk factor for gestational diabetes. However, the additional presence of TCF7L2 rs7903146 risk alleles does not further aggravate the negative impact of a history of gestational diabetes on metabolic traits related to T2DM. (C) 2018 Elsevier B.V. All rights reserved.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gestational Diabetes ; Type 2 Diabetes ; Oral Glucose Tolerance Test ; Tcf7l2 ; Insulin Sensitivity ; Liver Fat; Insulin-secretion; Risk; Polymorphisms; Glucose; Variants; Women; Sensitivity; Mellitus; Prevention; Resistance
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0168-8227
e-ISSN 1872-8227
Zeitschrift Diabetes Research and Clinical Practice
Quellenangaben Band: 146, Heft: , Seiten: 251-257 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
Institute of Epidemiology (EPI)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30202 - Environmental Health
Forschungsfeld(er) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP-Element(e) G-502400-001
G-521500-002
G-504091-002
G-501900-402
DOI 10.1016/j.diabres.2018.11.003
WOS ID WOS:000452704800029
Scopus ID 85056628200
PubMed ID 30419301
Erfassungsdatum 2018-11-19
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