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 and type 2 diabetes (IGT+T2D) and glycemic outcomes in youth from HAPO Follow-Up Study.

Research Design and Methods

We calculated T2D-GRS utilizing 1,150 known genetic variants associated with type 2 diabetes in adults. In utero exposures included gestational diabetes (GDM) and sum-of-glucose z-scores during oral glucose tolerance test at ~28 weeks gestation. IGT+T2D and continuous glycemic outcomes were measured at 10-14 years.

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 >75^th percentile, 15.9% had IGT+T2D compared to 5.6% in non-exposed.

Conclusions

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