title: Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.
abstract: 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.
  
  
  
  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.
  
  
  
  Matlab, a rural area in the Chittagong division of Bangladesh.
  
  
  
  Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Finer
authors.affiliation: Center for Control and Chronic disease' to Initiative for Non-Communicable Diseases (INCD), Health System and Population Studies Division, ICDDR,B, Dhaka, Bangladesh.
authors.forename: M S
authors.initials: MS
authors.lastname: Iqbal
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Lowe
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: B W
authors.initials: BW
authors.lastname: Ogunkolade
authors.affiliation: Center for Control and Chronic disease' to Initiative for Non-Communicable Diseases (INCD), Health System and Population Studies Division, ICDDR,B, Dhaka, Bangladesh.
authors.forename: S
authors.initials: S
authors.lastname: Pervin
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Mathews
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Smart
authors.affiliation: Center for Control and Chronic disease' to Initiative for Non-Communicable Diseases (INCD), Health System and Population Studies Division, ICDDR,B, Dhaka, Bangladesh.
authors.forename: D S
authors.initials: DS
authors.lastname: Alam
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, London, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Hitman
mesh_terms: D000328:Adult; D001459:Bangladesh; D015992:Body Mass Index; D001835:Body Weight; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D055106:Genome-Wide Association Study; D005951:Glucose Tolerance Test; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D012044:Regression Analysis; D012424:Rural Population; D013217:Starvation
keywords: Bangladesh; Developmental origins of health and disease; Epigenetics; Fetal programming; Malnutrition; South Asia