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.
- Fetal programming
- Developmental origins of health and disease
- South Asia
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↵* DSA and GAH are joint senior authors.
↵‡ MSI, RL and BWO are contributed equally.
Twitter Follow Sarah Finer at @Sarah_Finer
Contributors DA, GAH and SF conceived and designed the study. SP and DA recruited to and implemented the clinical study. SF and SI transferred samples from ICDDR,B to London, UK and performed DNA extraction and quality control checks. SF, SI, BWO and MS processed DNA for 450k analysis and bisulfite processing. SF analysed the clinical data with help from DA and GAH. RL and CM performed bioinformatics analysis with input from SF, VR and GAH. The manuscript was written by SF with help from BWO, GAH, SI, RL and DA.
Funding Medical Research Council (Clinical Research Training Fellowship; reference number G0800441) and ICDDR,B.
Competing interests None declared.
Ethics approval Ethical approval was obtained via standard institutional procedure (ICDDR,B) ethics review board, and peer review of study protocol at QMUL.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Extra data can be accessed via the Dryad data repository at http://datadryad.org/ with the doi:10.5061/dryad.k67kf.
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