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

IGF-1 and Leptin Associate With Fetal HDL Cholesterol at Birth Examination in Offspring of Mothers With Type 1 Diabetes Scott M. Nelson 1 , Dilys J. Freeman 1 , Naveed Sattar 2 , Frank D. Johnstone 3 and Robert S. Lindsay 2 1 Department of Reproductive and Maternal Medicine, University of Glasgow, Glasgow, Scotland, U.K 2 British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, U.K 3 Department of Obstetrics and Gynecology, University of Edinburgh, Centre for Reproductive Biology, Edinburgh, U.K Address correspondence and reprint requests to Dr. Scott M. Nelson, Department of Reproductive and Maternal Medicine, Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 ER, U.K. E-mail: s.nelson{at}clinmed.gla.ac.uk 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 su