Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study

Abstract

Background It has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent. Methods In this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex. Results Carrying a male fetus was associated with lower fasting glucose (difference in mean concentrations ≈ 0.1 mmol/L; β′ = 0.063; p = 0.02) and insulin (≈ 1.1 pmol/L; β′ = 0.075; p = 0.01) concentrations but not with post-load glucose or insulin concentrations. Male fetal sex was also associated with lower HOMA IR (≈ 1.08 units; β′ = 0.071; p = 0.02) and higher QUICKI (≈ 1.06 units; β′ = 0.080; p = 0.007) values suggesting increased basal insulin sensitivity. There were no differences in indices of insulin secretion, except for the insulin disposition index which was higher in women carrying a male fetus (≈ 1.15 units; β′ = 0.090; p = 0.007). Birth weights were higher in male offspring. Conclusions Women carrying a male fetus were relatively more insulin sensitive in the fasting state and secreted more insulin relative to this degree of insulin sensitivity. These results are consistent with the idea that the fetal sex may be able to modify the maternal glucose-insulin axis.

Maternal Gestational Diabetes Is Associated with High Risk of Childhood Overweight and Obesity: A Cross-Sectional Study in Pre-School Children Aged 2–5 Years

“…Interestingly, in our study, women who developed GDM exhibited a 27% greater incidence of delivering female children than male ones. Recent findings have demonstrated that fetal sex may exert a role on maternal insulin sensitivity [ 52 ]. In GDM, the placenta is affected, and different gene expression takes place, with fetal sex playing an important role [ 53 , 54 ].…”

“…Regarding GDM and fetal sex, Hooks et al [ 57 ] found that in women with GDM, having a male fetus raises the probability of preterm birth [ 55 ], while Seghieri et al [ 58 ] found that having a male fetus raises the likelihood of GDM, and in pregnancies with a female fetus, maternal obesity before gestation increases the probability of GDM. Another recent study found that having a male fetus is associated with higher insulin sensitivity [ 52 ]. Moreover, Mando et al explored the potential effect of GWG on fetal/placental ratio in overweight with different fetal gender and found different placenta adaptation depending on fetal sex, with substantial alterations merely in female fetuses [ 59 ].…”

Genetic Risk Factors and Gene–Lifestyle Interactions in Gestational Diabetes

“…Although current antenatal evaluation of GDM risk in pregnant women only involves the assessment of maternal characteristics, it is likely that also fetal, paternal, and/or placental factors affect its development and contribute to the observed heterogeneity in terms of obstetric and fetal outcomes [21]. The role of fetoplacental factors is suggested by epidemiological studies showing that GDM risk and/or maternal glycemia are affected by, e.g., fetal sex [73], multiple pregnancies [74], paternal age [75], and paternal ethnicity [76]. Moreover, a recent meta-analysis reported that GDM reoccurs only in approximately half of subsequent pregnancies [77]-less than what could be expected if GDM were only a sign of deranged glucose metabolism in the mother [21].…”

Sex differences in growth and mortality in pregnancy-associated hypertension

“…Males and females show differential expression of genes involved in several different functions in the placenta, providing a potential mechanism by which differential growth strategies could be achieved [11][12][13][14][15][16][17][18][19]. These could, in turn, contribute to sex differences in fetal oxygen extraction and maternal glucose metabolism [20,21].…”