Maternal glucose tolerance in pregnancy affects fetal insulin sensitivity.
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.


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). 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 beta-cell function.


RESULTS
Higher 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/microU/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.


CONCLUSIONS
Maternal glucose intolerance may impair fetal insulin sensitivity (but not beta-cell function) and consequently "program" the susceptibility to type 2 diabetes.
Luo
Zhong-Cheng
ZC
Department of Obstetrics and Gynecology, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada. zhong-cheng.luo@recherche-ste-justine.qc.ca
Delvin
Edgard
E
Fraser
William D
WD
Audibert
Francois
F
Deal
Cheri I
CI
Julien
Pierre
P
Girard
Isabelle
I
Shear
Roberta
R
Levy
Emile
E
Nuyt
Anne-Monique
AM
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000502:physiology; D005865:Gestational Age; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D011247:Pregnancy; D011384:Proinsulin / Q000097:blood; D011446:Prospective Studies
D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin