Placental structure in type 1 diabetes: relation to fetal insulin, leptin and IGF-I

  1. Scott M Nelson (s.nelson{at},
  2. Philip M Coan2,
  3. Graham J Burton2 and
  4. Robert S Lindsay3
  1. 1. Reproductive and Maternal Medicine, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER
  2. 2. Department of Physiology, Development and Neuroscience and the Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG
  3. 3. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA


    Objective: Alteration of placental structure may influence fetal overgrowth and complications of maternal diabetes. We examined the placenta in a cohort of offspring of mothers with type 1 diabetes (OT1DM) to assess structural changes and determine whether these were related to maternal HbA1c, fetal hematocrit, fetal hormonal or metabolic axes.

    Research Design and Methods: Placental samples were analysed using stereological techniques to quantify volumes and surface areas of key placental components in 88 OT1DM and 39 controls, and results related to maternal HbA1c and umbilical cord analytes (insulin, leptin, adiponectin, IGF-I, hematocrit, lipids, CRP, IL-6).

    Results: Intervillous space volume was increased in OT1DM (OT1DM 250±81 cm3 vs control 217±65cm3: P=0.02) with anisomorphic growth of villi (p=0.025). The placentae showed a trend to increased weight (OT1DM 690±19g; control 641±22g: P=0.08) but villous, non-parenchymal, trophoblast and capillary volumes did not differ. Villous surface area, capillary surface area, membrane thickness and calculated morphometric diffusing capacity were also similar in T1DM and controls. HbA1c at 26-34 weeks associated with birthweight (r=0.27, p=0.03), placental weight (r=0.41, p=0.0009) and intervillous space volume (r=0.38, p=0.0024). In multivariate analysis of cord parameters in OT1DM, fetal IGF-I emerged as a significant correlate of most components (intervillous space, villous, trophoblast, capillary volumes all P<0.01). By contrast fetal insulin was only independently associated with capillary surface area (positive, r2 6.7%; P=0.02).

    Conclusions: There are minimal placental structural differences between OT1DM and controls. Fetal IGF-I but not fetal insulin emerges as a key correlate of placental substructural volumes, thereby facilitating feedback to the placenta regarding fetal metabolic demand.


      • Received May 15, 2009.
      • Accepted July 30, 2009.