Differing Determinants of Overweight-Obesity and Glucose Intolerance in Offspring Born to Mothers with Diabetes During Pregnancy: Evidence from India

Background: Parental diabetes and obesity influence offspring phenotype, but their relative contributions remain unclear. Aim: To examine the relative contributions of parental diabetes and obesity to offspring overweight-obesity and glucose intolerance. Methods: We studied 200 offspring of mothers with diabetes in pregnancy (ODM; 176 indexes, 24 siblings), 176 mothers (133 gestational diabetes (GDM), 22 type 1, 21 type 2 diabetes), and 150 fathers. Controls included 177 offspring of non-diabetic mothers (ONDM), 177 mothers without diabetes in pregnancy, and 163 fathers. Overweight-obesity was defined by WHO criteria, central obesity as waist-to-height ratio >0.5, and glucose intolerance by ADA criteria (fasting glucose for <10 years; oral glucose tolerance test (OGTT) for >=10 years). Generalized linear mixed-effects models assessed parental determinants of offspring outcomes. Results: ODM were more overweight-obese, centrally obese, and glucose intolerant than ONDM. Younger ODM had higher capillary glucose (5.6 vs 5.1 mmol/L, p<0.001). Among ODM >=10 years, 37% had prediabetes and 5% diabetes versus 20% and 0% in ONDM. Overweight-obesity was associated with maternal (OR 7.81; 95% CI 2.19-27.85), paternal (OR 6.21; 95% CI 1.57-24.53), and biparental obesity (OR 9.59; 95% CI 2.73-33.69), but not parental diabetes. Glucose intolerance was associated only with maternal diabetes in pregnancy (OR 3.90; 95% CI 2.05-7.41). Conclusions: Preventing offspring obesity will require addressing parental obesity, whereas preventing glucose intolerance will require optimal glycemic control in the mothers before and during pregnancy.