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

ABSTRACT 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 a≥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.