Data from: Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study

Objectives Famine exposure in utero can ‘programme’ an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. Design A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed. Setting Matlab, a rural area in the Chittagong division of Bangladesh. Participants Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). Outcome measures Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. Results More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. Conclusions Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.

研究目标：宫内饥荒暴露可对个体产生“程序化”效应，使其晚年罹患2型糖尿病与肥胖的风险升高。本研究旨在明确三个核心问题：(1) 孟加拉国人群在发育阶段暴露于饥荒后，是否会被程序化导向糖尿病与肥胖表型；(2) 这种程序化效应是否特异性对应妊娠或产后暴露窗口；(3) 表观遗传差异是否与饥荒暴露存在关联。
研究设计：本研究为一项历史性队列研究，作为一项更大规模横断面调查的组成部分。饥荒暴露通过出生日期与历史记录进行界定，研究对象按以下三类筛选：(A) 产后阶段暴露于饥荒者；(B) 妊娠期间暴露于饥荒者；(C) 未暴露于饥荒者。
研究地点：孟加拉国吉大港专区的乡村地区马特拉巴(Matlab)。
研究对象：共纳入190名年轻成年男女作为研究对象，其中随机抽取的143名亚样本被纳入表观遗传研究。
结局指标：主要结局指标包括体重、体质量指数(BMI)以及口服葡萄糖耐量试验(0分钟与120分钟血糖值)。次要结局指标包括采用全基因组分析与靶向分析，对母系营养敏感的可变表位等位基因(metastable epialleles)的DNA甲基化水平。
结果：妊娠期间暴露于饥荒的年轻成年人中，体质量不足者比例高于产后暴露组与未暴露组。与之相反，产后暴露于饥荒的年轻成年人中，体质量超标者比例高于妊娠暴露组与未暴露组。与未暴露者相比，宫内妊娠阶段暴露于饥荒的体质量不足成年人，在葡萄糖耐量试验中表现为高血糖；而产后暴露者的空腹血糖水平升高。本研究鉴定出7个已知随妊娠饥荒暴露发生变化的可变表位等位基因(VTRNA2-1、PAX8、PRDM-9、ZFP57邻近区域、BOLA邻近区域、EXD3)，其DNA甲基化水平存在显著差异。
结论：发育阶段的饥荒暴露可使孟加拉国子代在成年后罹患糖尿病与肥胖，但妊娠与产后暴露窗口对表型的影响存在差异。本研究在既往已报道的与围受孕期饥荒暴露敏感的可变表位等位基因中，重复验证了DNA甲基化差异。