title: Birth weight, genetic susceptibility, and adulthood risk of type 2 diabetes.
abstract: OBJECTIVE
  Both stressful intrauterine milieus and genetic susceptibility have been linked to later-life diabetes risk. The current study aims to examine the interaction between low birth weight, a surrogate measure of stressful intrauterine milieus, and genetic susceptibility in relation to risk of type 2 diabetes in adulthood.
  
  
  METHODS
  The analysis included two independent, nested case-control studies of 2,591 type 2 diabetic case subjects and 3,052 healthy control subjects. We developed two genotype scores: an obesity genotype score based on 32 BMI-predisposing variants and a diabetes genotype score based on 35 diabetes-predisposing variants.
  
  
  RESULTS
  Obesity genotype scores showed a stronger association with type 2 diabetes risk in individuals with low birth weight. In low-birth weight individuals, the multivariable-adjusted odds ratio (OR) was 2.55 (95% CI 1.34-4.84) by comparing extreme quartiles of the obesity genotype score, while the OR was 1.27 (1.04-1.55) among individuals with birth weight >2.5 kg (P for interaction = 0.017). We did not observe significant interaction between diabetes genotype scores and birth weight with regard to risk of type 2 diabetes. In a comparison of extreme quartiles of the diabetes gene score, the multivariable-adjusted OR was 3.80 (1.76-8.24) among individuals with low birth weight and 2.27 (1.82-2.83) among those with high birth weight (P for interaction = 0.16).
  
  
  CONCLUSIONS
  Our data suggest that low birth weight and genetic susceptibility to obesity may synergistically affect adulthood risk of type 2 diabetes.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.forename: Tsegaselassie
authors.initials: T
authors.lastname: Workalemahu
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D001724:Birth Weight / Q000502:physiology*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011795:Surveys and Questionnaires