Maternal BMI Before Pregnancy, Maternal Weight Gain During Pregnancy, and Risk of Persistent Positivity for Multiple Diabetes-Associated Autoantibodies in Children With the High-Risk HLA Genotype: The MIDIA study

OBJECTIVE: To assess whether maternal BMI before pregnancy and weight gain during pregnancy predicted the risk of islet autoimmunity in genetically susceptible children. RESEARCH DESIGN AND METHODS: Of 46,939 newborns screened for the high-risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma-associated protein 2 (IA2). The end point was defined as repeated positivity for two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity). RESULTS: Thirty-six children developed islet autoimmunity, of whom 10 developed type 1 diabetes. Both maternal BMI greater-than-or-equal30 kg/m² before pregnancy and maternal weight gain greater-than-or-equal15 kg predicted the increased risk of islet autoimmunity (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively), independent of maternal diabetes. CONCLUSIONS: Maternal weight may predict risk of islet autoimmunity in offspring with a high genetic susceptibility for type 1 diabetes.