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Diabetes Res Clin Pract. 2018 Dec;146:251-257. doi: 10.1016/j.diabres.2018.11.003. Epub 2018 Nov 10.

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

Author information

1
Division of Endocrinology, Diabetology, Nephrology, Angiology and Clinical Chemistry, Eberhardt Karls University, Tuebingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen (IDM), Tuebingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
2
German Center for Diabetes Research (DZD), Neuherberg, Germany; Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; Clinical Cooperation Group Type 2 Diabetes, Helmholtz Center Munich, Neuherberg, Germany.
3
German Center for Diabetes Research (DZD), Neuherberg, Germany; Diabetes Research Group, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; Research Unit of Molecular Epidemiology, Institute for Epidemiology II, Helmholtz Center Munich, Neuherberg, Germany.
4
Division of Endocrinology, Diabetology, Nephrology, Angiology and Clinical Chemistry, Eberhardt Karls University, Tuebingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen (IDM), Tuebingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Electronic address: fritsche@med.uni-tuebingen.de.

Abstract

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.

KEYWORDS:

Gestational diabetes; Insulin sensitivity; Liver fat; Oral glucose tolerance test; TCF7L2; Type 2 diabetes

PMID:
30419301
DOI:
10.1016/j.diabres.2018.11.003
[Indexed for MEDLINE]

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