title: Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.
abstract: OBJECTIVE
  Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity.
  
  
  METHODS
  Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined.
  
  
  RESULTS
  Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03).
  
  
  CONCLUSIONS
  Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.
authors.affiliation: Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Linder
authors.forename: Franziska
authors.initials: F
authors.lastname: Schleger
authors.forename: Caroline
authors.initials: C
authors.lastname: Ketterer
authors.forename: Louise
authors.initials: L
authors.lastname: Fritsche
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kiefer-Schmidt
authors.forename: Anita
authors.initials: A
authors.lastname: Hennige
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Hubert
authors.initials: H
authors.lastname: Preissl
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000502:physiology*; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; D007328:Insulin