Objective: Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or beta cell function.

Research design and methods: In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin and proinsulin concentrations in maternal blood at the 50 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation, and in venous cord blood (n=248). Cord blood glucose/insulin ratio and proinsulin concentration were used as indicators of fetal insulin sensitivity, and proinsulin/insulin ratio as an indicator of fetal beta cell function.

Results: Higher OGTT blood glucose levels were associated with significantly lower cord plasma glucose/insulin ratios (r= −0.31, p<0.001) and higher proinsulin concentrations (r= 0.31, p<0.001), but not associated with proinsulin/insulin ratios. Comparing gestational diabetic (n=26) vs. euglycemic pregnancy, cord blood glucose/insulin ratios were substantially lower (geometric mean: 10.1 vs. 20.0 mg/dl/μU/ml, p<0.001), while proinsulin concentrations much higher (24.4 vs. 13.8 pmol/L, p<0.001), despite similar cord blood glucose concentrations indicating adequate management of diabetes. The differences remained significant after controlling for pre-pregnancy and fetal adiposity, family history of diabetes, gestational age and other potential confounders. Significant changes in glucose/insulin ratio and proinsulin concentration were also observed in obese (n=31) mothers, but the differences became not statistically significant after adjusting for maternal glucose tolerance and fetal adiposity.

Conclusions: Maternal glucose intolerance may impair fetal insulin sensitivity (but not beta cell function), and consequently “program” the susceptibility to type 2 diabetes.