Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
Diabetes Care. 2012 Dec;35(12):2479-84. doi: 10.2337/dc12-0168. Epub 2012 Aug 24.
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.
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.
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).
Our data suggest that low birth weight and genetic susceptibility to obesity may synergistically affect adulthood risk of type 2 diabetes.
紧张的宫内环境和遗传易感性都与晚年糖尿病风险有关。本研究旨在探讨低出生体重（宫内环境紧张的替代指标）与遗传易感性之间的相互作用与成年后患 2 型糖尿病的风险。
该分析包括两项独立的嵌套病例对照研究，共纳入 2591 名 2 型糖尿病病例和 3052 名健康对照。我们开发了两种基因型评分：基于 32 个 BMI 易感变异的肥胖基因型评分和基于 35 个糖尿病易感变异的糖尿病基因型评分。
肥胖基因型评分与低出生体重个体的 2 型糖尿病风险相关性更强。在低出生体重个体中，肥胖基因型评分的四分位距最高和最低两组间比较，多变量校正后的比值比（OR）为 2.55（95%CI 1.34-4.84），而出生体重>2.5kg 的个体中 OR 为 1.27（1.04-1.55）（交互作用 P=0.017）。我们没有观察到糖尿病基因型评分与出生体重之间存在显著的交互作用与 2 型糖尿病风险相关。在比较糖尿病基因评分的四分位距最高和最低两组间，低出生体重个体的多变量校正后的 OR 为 3.80（1.76-8.24），而出生体重较高的个体中 OR 为 2.27（1.82-2.83）（交互作用 P=0.16）。
我们的数据表明，低出生体重和肥胖遗传易感性可能协同影响成年后患 2 型糖尿病的风险。
