In Utero Exposure to Maternal Hyperglycemia and Offspring Type 2 Diabetes Genetic Risk Score Are Independently Associated With Risk of Impaired Glucose Tolerance in Youth.

Objective: We tested associations of type 2 diabetes genetic risk score (T2D-GRS) and exposure to maternal hyperglycemia with childhood impaired glucose tolerance (IGT) and T2D and glycemic outcomes in youth from the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study.

Research design and methods: We calculated T2D-GRS using 1,150 known genetic variants associated with T2D in adults. In utero exposures included gestational diabetes mellitus (GDM) and sum-of-glucose z scores during oral glucose tolerance test at ∼28 weeks' gestation. IGT + T2D and continuous glycemic outcomes were measured when children were 10-14 years old.

Results: In 3,444 children (mean age, 11.4 years), higher maternal sum-of-glucose z scores and child T2D-GRS were both associated with higher glucose levels. In children exposed to GDM and with T2D-GRS >75th percentile, 15.9% had IGT + T2D, compared with 5.6% in nonexposed children.

Conclusions: High genetic risk for diabetes and in utero exposure to maternal hyperglycemia are additively associated with IGT + T2D and glycemic outcomes in youth.