Hyperglycemia and adverse Pregnancy Outcome follow-up study (HAPO FUS): Maternal glycemia and childhood glucose metabolism

Objective
Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.
Research Design and Methods
HAPO Follow-Up Study (FUS) included 4160 children ages 10-14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ~28 weeks gestation with blinded glucose values. Primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index.
Results
For GDM mothers, 10.6% of children had IGT compared with 5.0% of children of
mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2
diabetes cases (10) were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI and child BMI z-score were 1.09 (0.78-1.52) for IFG and 1.96 (1.41-2.73) for IGT. GDM was positively associated with child’s 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index [adjusted mean differences (95% CI) -76.3 (-130.3- -22.4) and -0.12 (-0.17- -0.064)], respectively, but not insulinogenic index.
Conclusions
Offspring exposed to untreated GDM in utero are insulin resistant with limited beta cell compensation compared with offspring of non-GDM mothers. GDM is significantly and
independently associated with childhood IGT.