title: Placental structure in type 1 diabetes: relation to fetal insulin, leptin, and IGF-I.
abstract: 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 A1C, fetal hematocrit, fetal hormonal, or metabolic axes.
  
  
  METHODS
  Placental samples were analyzed using stereological techniques to quantify volumes and surface areas of key placental components in 88 OT1DM and 39 control subjects, and results related to maternal A1C and umbilical cord analytes (insulin, leptin, adiponectin, IGF-I, hematocrit, lipids, C-reactive protein, and interleukin-6).
  
  
  RESULTS
  Intervillous space volume was increased in OT1DM (OT1DM 250 + or - 81 cm(3) vs. control 217 + or - 65 cm(3); P = 0.02) with anisomorphic growth of villi (P = 0.025). The placentas showed a trend to increased weight (OT1DM 690 + or - 19 g; control 641 + or - 22 g; P = 0.08), but villous, nonparenchymal, trophoblast, and capillary volumes did not differ. Villous surface area, capillary surface area, membrane thickness, and calculated morphometric diffusing capacity were also similar in type 1 diabetic and control subjects. A1C at 26-34 weeks associated with birth weight (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, and capillary volumes, all P < 0.01). By contrast, fetal insulin was only independently associated with capillary surface area (positive, r(2) = 6.7%; P = 0.02).
  
  
  CONCLUSIONS
  There are minimal placental structural differences between OT1DM and control subjects. 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.
authors.affiliation: Department of Reproductive and Maternal Medicine, University of Glasgow, Glasgow, U.K. s.nelson@clinmed.gla.ac.uk
authors.forename: Scott M
authors.initials: SM
authors.lastname: Nelson
authors.forename: Philip M
authors.initials: PM
authors.lastname: Coan
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Burton
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lindsay
mesh_terms: D052242:Adiponectin / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry* / Q000502:physiology*; D005333:Fetus / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006400:Hematocrit; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D011384:Proinsulin / Q000097:blood
chemical_list: D052242:Adiponectin; D005938:Glucocorticoids; D006442:Glycated Hemoglobin; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D020738:Leptin; D011384:Proinsulin
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