PDF(Pubmed)
Abstract：
OBJECTIVE: Gene-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.
METHODS: The 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.
RESULTS: Logistic 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.
CONCLUSIONS: Simultaneous 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.
METHODS: The 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.
RESULTS: Logistic 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.
CONCLUSIONS: Simultaneous 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.
摘要：
目的：基因与环境的相互作用被认为对2型糖尿病的发展有重要影响；然而，潜在的机制和具体的相互作用仍不清楚.考虑到受宫内环境影响的低出生体重（LBW）患病率不断增加，我们试图调查与LBW患者2型糖尿病发展相关的遗传因素。
方法：在一个以人群为基础的日本队列（n=1,021）中，20个报道的2型糖尿病易感基因与LBW（<2,500g）个体2型糖尿病发展之间的相互作用通过逻辑回归和分层分析。
结果：Logistic回归分析表明，只有抵抗素基因（RETN）的rs1862513位点的G/G基因型，胰岛素抵抗的既定发起者，与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的分层分析显示，LBW和RETNG/G基因型对空腹胰岛素有显著的交互作用，稳态模型评估2-胰岛素抵抗，Matsuda指数与2型糖尿病患病率（所有P值交互作用<0.05）。与非LBW+非G/G基因型组相比，LBW+G/G基因型组2型糖尿病的校正比值比为7.33(95%置信区间2.43-22.11；P=0.002)。在排除了第二次世界大战造成的营养不良的影响后，也获得了类似的结果。
结论：同时评估LBW和RETNG/G基因型比单独评估这些因素更准确地预测未来2型糖尿病的风险，并提供管理策略，包括对LBW人群的早期生活方式干预。
方法：在一个以人群为基础的日本队列（n=1,021）中，20个报道的2型糖尿病易感基因与LBW（<2,500g）个体2型糖尿病发展之间的相互作用通过逻辑回归和分层分析。
结果：Logistic回归分析表明，只有抵抗素基因（RETN）的rs1862513位点的G/G基因型，胰岛素抵抗的既定发起者，与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的分层分析显示，LBW和RETNG/G基因型对空腹胰岛素有显著的交互作用，稳态模型评估2-胰岛素抵抗，Matsuda指数与2型糖尿病患病率（所有P值交互作用<0.05）。与非LBW+非G/G基因型组相比，LBW+G/G基因型组2型糖尿病的校正比值比为7.33(95%置信区间2.43-22.11；P=0.002)。在排除了第二次世界大战造成的营养不良的影响后，也获得了类似的结果。
结论：同时评估LBW和RETNG/G基因型比单独评估这些因素更准确地预测未来2型糖尿病的风险，并提供管理策略，包括对LBW人群的早期生活方式干预。
