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

Examination in Offspring of Mothers With Type 1 Diabetes

  1. Scott M. Nelson1,
  2. Dilys J. Freeman1,
  3. Naveed Sattar2,
  4. Frank D. Johnstone3 and
  5. Robert S. Lindsay2
  1. 1Department of Reproductive and Maternal Medicine, University of Glasgow, Glasgow, Scotland, U.K
  2. 2British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, U.K
  3. 3Department of Obstetrics and Gynecology, University of Edinburgh, Centre for Reproductive Biology, Edinburgh, U.K
  1. 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 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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 31 July 2007. DOI: 10.2337/db07-0585.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0585.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received April 27, 2007.
    • Accepted July 24, 2007.
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  1. Diabetes vol. 56 no. 11 2705-2709
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