Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity - A study of discordant sibships

Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine di abetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born be fore and one after the mother was diagnosed with type 2 diabetes were selec ted. Consequently, the siblings born before and after differed in their exp osure to diabetes in utero. A total of 58 siblings from 19 families in whic h at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born aft er the mother developed diabetes than in those born before the mother's dia gnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 si blings without diabetes, the mean BMI was 2.6 kg/m(2) higher in offspring o f diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In con trast, there were no significant differences in risk of diabetes or BMI bet ween offspring born before and after the father was diagnosed with diabetes . Intrauterine exposure to diabetes per se conveys a high risk for the deve lopment of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone.