Aims/IntroductionGene–environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW.Materials and MethodsThe interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population‐based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses.ResultsLogistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index‐adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2‐insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P‐values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43–22.11; P = 0.002) compared with the non‐LBW + non‐G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II.ConclusionsSimultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

中文翻译：

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低出生体重和抵抗素基因 rs1862513 变异对成年期胰岛素抵抗和 2 型糖尿病的相互作用：香椿基因组研究

目的/简介基因与环境的相互作用被认为对 2 型糖尿病的发展有重大影响；然而，潜在的机制和具体的相互作用仍不清楚。鉴于受宫内环境影响的低出生体重 (LBW) 患病率不断增加，我们试图调查 LBW 个体中与 2 型糖尿病发展相关的遗传因素。材料和方法20 个已报道的 2 型糖尿病易感基因与 2 型糖尿病发展之间的相互作用在基于人群的日本队列中，LBW（<2,500 g）个体中患有 2 型糖尿病（n= 1,021）通过逻辑回归和分层分析进行检验。结果逻辑回归分析表明，只有女/女抵抗素基因 rs1862513 位点的基因型（视网膜色素变性）是胰岛素抵抗的既定引发因素，与 LBW 个体中 2 型糖尿病的患病率密切相关。年龄、性别和当前体重指数调整后的分层分析显示，LBW 和体重之间存在显着的交互作用。RETN G/G空腹胰岛素基因型、稳态模型评估 2-胰岛素抵抗、松田指数和 2 型糖尿病患病率（全部磷‐交互作用值<0.05）。LBW + 中 2 型糖尿病的调整优势比女/女基因型组为 7.33（95% 置信区间 2.43–22.11；磷= 0.002) 与非 LBW + 非女/女基因型组。排除二战造成营养不良的影响后，也得到了类似的结果。 结论同时评估低体重和体重RETN G/G与单独评估这些因素相比，基因型可以更准确地预测未来患 2 型糖尿病的风险，并提供管理策略，包括对 LBW 人群进行早期生活方式干预。