Maternal Glucose Tolerance in Pregnancy Affects Fetal Insulin Sensitivity

Abstract

OBJECTIVEOffspring 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 β-cell function.RESEARCH DESIGN AND METHODSIn 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). The cord blood glucose-to-insulin ratio and proinsulin concentration were used as indicators of fetal insulin sensitivity and the proinsulin-to-insulin ratio was used as an indicator of fetal β-cell function.RESULTSHigher OGTT blood glucose levels were associated with significantly lower cord plasma glucose-to-insulin ratios (r = −0.31, P < 0.001) and higher proinsulin concentrations (r = 0.31, P < 0.001) but not with proinsulin-to-insulin ratios. In a comparison of gestational diabetic (n = 26) versus euglycemic pregnancy, cord blood glucose-to-insulin ratios were substantially lower (geometric mean 10.1 vs. 20.0 mg/dl/μU/ml; P < 0.001), whereas proinsulin concentrations were 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 prepregnancy and fetal adiposity, family history of diabetes, gestational age, and other potential confounders. Significant changes in the glucose-to-insulin ratio and proinsulin concentration were also observed in obese (n = 31) mothers, but the differences became not statistically significant after adjustment for maternal glucose tolerance and fetal adiposity.CONCLUSIONSMaternal glucose intolerance may impair fetal insulin sensitivity (but not β-cell function) and consequently “program” the susceptibility to type 2 diabetes.

Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

“…Cord plasma DHA (but not AA) levels were significantly lower in the newborns of gestational diabetic pregnancies than non-diabetic pregnancies (∼ 17.1% lower in relative weight, P  = 0.01) ( Table 2 ), despite similar cord blood glucose concentrations (4.6 vs. 4.8 mmol/L, P  = 0.47) indicating adequate management of diabetes in the study cohort [17]. A similar pattern was observed for eicosapentaenoic acid (EPA; C20∶5n-3; ∼33.3% lower in gestational diabetic pregnancies, P  = 0.02).…”

“…In a prospective singleton pregnancy cohort study in Montreal, Canada, we have shown that gestational diabetes may impair fetal insulin sensitivity [17]. To further study the potential impact of fatty acids on fetal insulin sensitivity, maternal and cord plasma specimens were used to measure fatty acids in a subset of the cohort.…”

Maternal and Fetal IGF-I and IGF-II Levels, Fetal Growth, and Gestational Diabetes

“…Insulin is the primary driver of fetal IGF-I production (2). The higher fetal IGF-I levels in gestational diabetes could be attributable to elevated fetal insulin secretion (15,16). We speculated that the higher maternal IGF-I levels in gestational diabetes could be due to enhanced secretion of placental GH, the main driver of maternal IGF-I production in pregnancy (9).…”

“…Maternal and cord blood specimens from a recent prospective pregnancy cohort study (15) were used to investigate maternal and fetal IGF-I and IGF-II levels and their associations with fetal growth. The study was approved by the research ethics committees of participating hospitals.…”

“…Levels of maternal and fetal insulin secretion are elevated in gestational diabetic vs. euglycemic pregnancies (15,16). Studies have been limited and conflicting concerning whether maternal and fetal IGF-I levels are elevated in gestational diabetic pregnancies (17)(18)(19), whereas there is a scarcity of data on IGF-II.…”