IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth

Abstract

OBJECTIVE— Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures. RESEARCH DESIGN AND METHODS— We performed an observational study measuring fetal, HDL, and LDL cholesterol; triglycerides; and nonesterified fatty acids (NEFAs) in a total of 139 OT1DM and 48 control subjects at birth and assessed cross-sectional relationships with birth weight, fetal insulin, leptin, adiponectin, and IGF-1. RESULTS— Concentrations of total cholesterol (male OT1DM [mean ± SD] 1.49 ± 0.45 mmol/l and male control subjects 1.74 ± 0.33 mmol/l; P < 0.001), HDL cholesterol (0.53 ± 0.21 and 0.74 ± 0.19 mmol/l, respectively; P < 0.001), and NEFA (median 0.17 [interquartile range 2.30−2.95] and 0.21 [0.18–0.36], respectively; P < 0.001) were significantly lower in male OT1DM, with no significant differences in female subjects. Differences in male subjects were independent of mode of delivery. Cord lipids were unrelated to birth weight in OT1DM and did not show consistent relationships with fetal insulin. Unexpectedly, IGF-1 was a strong correlate of HDL cholesterol in control subjects (r = 0.40, P = 0.002) and OT1DM (r = 0.32, P < 0.001) but a negative correlate of triglycerides in control subjects (r = −0.48, P < 0.001) and OT1DM (r = −0.21, P = 0.004), with these relationships present in both sexes. In OT1DM, leptin was also independently correlated (negatively, P < 0.001) with HDL cholesterol in male and female subjects. CONCLUSIONS— Maternal diabetes is associated with significant alterations in lipid levels in male fetuses. IGF-1, leptin, and male sex rather than insulin may be the major determinants of HDL cholesterol and triglycerides in utero.