IGF-1 and leptin associate with fetal HDL-cholesterol at birth: examination in offspring of mothers with type 1 diabetes

  1. Scott M. Nelson, BSc, PhD, MRCOG (s.nelson{at}clinmed.gla.ac.uk)1,
  2. Dilys J. Freeman, BSc, PhD2,
  3. Naveed Sattar, PhD, FRCPath, FRCP (Glasg)3,
  4. Frank D. Johnstone, MD, FRCOG4 and
  5. Robert S. Lindsay, BSc, PhD, FRCP (Glasg)5
  1. 1Reproductive and Maternal Medicine, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER
  2. 2Reproductive and Maternal Medicine, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER
  3. 3BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA
  4. 4Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, Edinburgh EH3 9ET
  5. 5BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA

    Abstract

    Objective: Offspring of mothers with type 1 diabetes mellitus (OT1DM) demonstrate increased fat deposition, hyperinsulinaemia and hyperleptinaemia 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: Observational study measuring fetal cholesterol, HDL-C, LDL-C, TG and non-esterified fatty acids (NEFA) in a total of 139 OT1DM and 48 controls at birth and assessing cross sectional relationships with birth weight, fetal insulin, leptin, adiponectin and IGF-1.

    Results: Concentrations of total cholesterol (OT1DM male 1.49 ± 0.45 mmol/l; Control male 1.74 ± 0.33 mmol/l; P<0.001), HDL-C (OT1DM male 0.53 ± 0.21 mmol/l; Control male 0.74 ± 0.19 mmol/l; P<0.001) and NEFA (OT1DM male 0.17 [2.30 -2.95]; Control 0.21 [0.18 – 0.36], P<0.001) were significantly lower in male OT1DM with no significant differences in females. Differences in males were independent of mode of delivery. Cord lipids were unrelated to birthweight in OT1DM, and did not show consistent relationships with fetal insulin. Unexpectedly, IGF-1 was a strong correlate of HDL-C in controls (r=0.40, P=0.002) and OT1DM (r=0.32, p<0.001) and a negative correlate of TG in controls (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-C in males and females.

    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-C and Triglyceride in-utero.

    Footnotes

      • Received April 27, 2007.
      • Accepted July 24, 2007.

    This Article

    1. Diabetes
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