Metabolic phenotyping by treatment modality in obese women with gestational diabetes suggests diverse pathophysiology: An exploratory study

White, S. L. et al. (2020) Metabolic phenotyping by treatment modality in obese women with gestational diabetes suggests diverse pathophysiology: An exploratory study. PLoS ONE, 15(4), e0230658. (doi: 10.1371/journal.pone.0230658) (PMID:32240196) (PMCID:PMC7117764)

Abstract

Background and purpose: Excess insulin resistance is considered the predominant pathophysiological mechanism in obese women who develop gestational diabetes (GDM). We hypothesised that obese women requiring differing treatment modalities for GDM may have diverse underlying metabolic pathways. Methods: In this secondary analysis of the UK pregnancies Better Eating and Activity Trial (UPBEAT) we studied women from the control arm with complete biochemical data at three gestational time points; at 15–18+6 and 27–28+6 weeks (before treatment), and 34–36+0 weeks (after treatment). A total of 89 analytes were measured (plasma/serum) using a targeted nuclear magnetic resonance (NMR) platform and conventional assays. We used linear regression with appropriate adjustment to model metabolite concentration, stratified by treatment group. Main findings: 300 women (median BMI 35kg/m2; inter quartile range 32.8–38.2) were studied. 71 developed GDM; 28 received dietary treatment only, 20 metformin, and 23 received insulin. Prior to the initiation of treatment, multiple metabolites differed (p<0.05) between the diet and insulin-treated groups, especially very large density lipoprotein (VLDL) and high density lipoprotein (HDL) subclasses and constituents, with some differences maintained at 34–36 weeks’ gestation despite treatment. Gestational lipid profiles of the diet treatment group were indicative of a lower insulin resistance profile, when compared to both insulin-treated women and those without GDM. At 28 weeks’ the diet treatment group had lower plasma fasting glucose and insulin than women treated with insulin, yet similar to those without GDM, consistent with a glycaemic mechanism independent of insulin resistance. Conclusions/Interpretation: This exploratory study suggests that GDM pathophysiological processes may differ amongst obese women who require different treatment modalities to achieve glucose control and can be revealed using metabolic profiling.

• Item Type: Articles
• Additional Information: Funding: This study received funding from the National Institute of Health Research (www.nihr.ac. uk) (RP-PG-0407-10452), Medical Research Council UK (www.mrc.ac.uk) (MR/ L002477/1), Chief Scientist Office, Scottish Government Health Directorates (Edinburgh) (www.cso.scot.nhs.uk) (CZB/A/680), Biomedical Research Centre at Guys and St Thomas NHS Foundation Trust and King’s College London (www.guysandstthomasbrc.nihr. ac.uk) and the NIHR Bristol Biomedical Research Centre (www.bristolbrc.nihr.ac.uk), Tommy’s Charity, UK (www.tommys.org) (SC039280). SLW was supported by a fellowship from Diabetes UK (www.diabetes.org.uk) (14/ 0004849). DP was funded by Tommy’s Charity. MCV was supported by a fellowship from CAPES-Brazil (www.iie.org/ programs/CAPES) (BEX 9571/13-2). DAL’s contribution to this work was supported by the European Union’s Seventh Framework Programme (www.ec.europa.eu/research/fp7) (FP7/2007- 2013), ERC grant agreement (www.erc.europa.eu) (No 669545, DevelopObese) and the US National Institute of Health (www.nih.gov) (R01 DK10324) and is a National Institute for Health research Senior Investigator (NF-SI-0166-10196) and LP is an Emeritus National Institute for Health Research Senior Investigator (NI-SI-0512-10104).
• Keywords: Medicine and health sciences, Biology and life sciences.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nelson, Professor Scott and Welsh, Professor Paul and Sattar, Professor Naveed

Creator Roles

Sattar, N.: Conceptualization, Funding acquisition, Methodology, Writing – review and editing
Nelson, S.: Conceptualization, Funding acquisition, Methodology, Writing – review and editing
Welsh, P.: Investigation, Writing – review and editing

• Authors: White, S. L., Begum, S., Vieira, M. C., Seed, P., Lawlor, D. L., Sattar, N., Nelson, S. M., Welsh, P., Pasupathy, D., Poston, L., and on behalf of UPBEAT Consortium,
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2020 White et al.
• First Published: First published in PLoS ONE 15(4):e0230658
• Publisher Policy: Reproduced under a Creative Commons Licence