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Diabetes Care. 2012 Dec;35(12):2479-84. doi: 10.2337/dc12-0168. Epub 2012 Aug 24.

Birth weight, genetic susceptibility, and adulthood risk of type 2 diabetes.

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  • 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

OBJECTIVE:

Both stressful intrauterine milieus and genetic susceptibility have been linked to later-life diabetes risk. The current study aims to examine the interaction between low birth weight, a surrogate measure of stressful intrauterine milieus, and genetic susceptibility in relation to risk of type 2 diabetes in adulthood.

RESEARCH DESIGN AND METHODS:

The analysis included two independent, nested case-control studies of 2,591 type 2 diabetic case subjects and 3,052 healthy control subjects. We developed two genotype scores: an obesity genotype score based on 32 BMI-predisposing variants and a diabetes genotype score based on 35 diabetes-predisposing variants.

RESULTS:

Obesity genotype scores showed a stronger association with type 2 diabetes risk in individuals with low birth weight. In low-birth weight individuals, the multivariable-adjusted odds ratio (OR) was 2.55 (95% CI 1.34-4.84) by comparing extreme quartiles of the obesity genotype score, while the OR was 1.27 (1.04-1.55) among individuals with birth weight >2.5 kg (P for interaction = 0.017). We did not observe significant interaction between diabetes genotype scores and birth weight with regard to risk of type 2 diabetes. In a comparison of extreme quartiles of the diabetes gene score, the multivariable-adjusted OR was 3.80 (1.76-8.24) among individuals with low birth weight and 2.27 (1.82-2.83) among those with high birth weight (P for interaction = 0.16).

CONCLUSIONS:

Our data suggest that low birth weight and genetic susceptibility to obesity may synergistically affect adulthood risk of type 2 diabetes.

PMID:
22923665
[PubMed - indexed for MEDLINE]
PMCID:
PMC3507591
Free PMC Article
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