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Insulin and The Brain

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Front. Endocrinol. | doi: 10.3389/fendo.2018.00673

Family History Of Diabetes Is Associated With Delayed Fetal Postprandial Brain Activity

 Franziska Schleger1, 2, 3, Katarzyna Linder1, 2, 3, 4, Laura Walter4,  Martin Heni1, 2, 3, 4,  Johanna Brändle4,  Sara Y. Brucker4, Jan Pauluschke-Fröhlich4, Magdalene Weiss4, Hans-Ulrich Häring1, 2, 3, 4,  Hubert Preissl1, 2, 3, 4, 5* and  Andres Fritsche1, 2, 3, 4
  • 1IDO Institute for Diabetes and Obesity, Helmholtz Zentrum München, Germany
  • 2IDO Institute for Diabetes and Obesity, Helmholtz Zentrum München, Germany
  • 3Deutsche Zentrum für Diabetesforschung (DZD), Germany
  • 4Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Universitätsklinikum Tübingen, Universität Tübingen, Germany
  • 5Department of Pharmacy and Biochemistry, Universität Tübingen, Germany

Introduction. We have previously shown that fetuses of mothers with gestational diabetes mellitus (GDM) and insulin resistance exhibit a prolongation of fetal auditory event-related brain responses (fAER) compared to fetuses of normal glucose tolerant women during an oral glucose tolerance test (oGTT). This implies that maternal metabolism may program the developing fetal brain. We now asked whether a family history of type 2 diabetes without metabolic programing also impacts fetal brain activity. We therefore investigated brain activity in fetuses of normal glucose tolerant mothers with and without family history of type 2 diabetes (FHD+ and FHD-).

Methods. A 75g oGTT was performed in healthy pregnant women. Plasma glucose and insulin levels were measured after 0, 60 and 120 minutes. Each blood draw was preceded by magnetoencephalographic recordings of fAER. From a group of 167 participants, a sub-sample of 52 metabolically healthy women, 37 with a negative and 15 with a positive FHD (at least one first- or second-degree relative) was carefully selected based on the following inclusion criteria: inconspicuous pregnancy, no GDM, BMI 18.5-30 kg/m², no preterm birth and at least two fMEG with detectable fetal responses during oGTT.

Results. An ANOVA showed a significant interaction between fMEG measurement time during the OGTT and FHD on fAER latency (F(2) =4.163, p=0.018). Fetuses of mothers with FHD+ had a prolonged fAER (273±113ms) compared to fetuses of mothers with FHD- (219±69ms) at 60 minutes during the oGTT (F(1)=4.902, p=0.032). There were no significant differences in age, BMI before pregnancy, weight gain during pregnancy and gestational age between the groups. Maternal glucose levels and insulin sensitivity were also not significantly different.

Discussion. In addition to the previously shown influence of maternal metabolism on fetal brain activity, maternal family history of diabetes is also linked to fetal postprandial brain activity. This indicates that genetic and/or epigenetic factors modulate the postprandial brain response of the developing fetus.

Keywords: Fetal MEG, OGTT Oral glucose tolerance test, family history, type 2 diabetes, Maternal metabolism, fetal programming

Received: 26 Jul 2018; Accepted: 29 Oct 2018.

Edited by:

Mohammed Taouis, UMR9197 Institut des Neurosciences Paris Saclay (Neuro-PSI), France

Reviewed by:

Angel Nadal, Universidad Miguel Hernández de Elche, Spain
Sarah H. Lockie, Monash University, Australia  

Copyright: © 2018 Schleger, Linder, Walter, Heni, Brändle, Brucker, Pauluschke-Fröhlich, Weiss, Häring, Preissl and Fritsche. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Hubert Preissl, IDO Institute for Diabetes and Obesity, Helmholtz Zentrum München, Garching bei München, Baden-Württemberg, Germany,