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. 2020 Apr 2;15(4):e0230658.
doi: 10.1371/journal.pone.0230658. eCollection 2020.

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

Sara L White  1 , Shahina Begum  1 , Matias C Vieira  1 , Paul Seed  1 , Deborah L Lawlor  2   3   4 , Naveed Sattar  5 , Scott M Nelson  6 , Paul Welsh  5 , Dharmintra Pasupathy  1 , Lucilla Poston  1 ; UPBEAT Consortium
Affiliations

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

Sara L White et al. PLoS One. .

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.

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Conflict of interest statement

SMN and LP disclose receipt of lecture/other fees from Roche Diagnostics, outside the scope of this work. DAL discloses receipt of fees from Roche Diagnostics and Ferring Pharmaceuticals for research unrelated to this paper. All other authors declare that there is no declaration of interest associated with their contribution to this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Metabolite SD difference between GDM treatment groups compared to No-GDM women at time point 1, 10 weeks before diagnosis/treatment (mean 17+0 weeks’).
Data points show the standard deviation (SD) difference between treatment group and No-GDM women. Positive differences compared to No-GDM are shown to the right, negative to the left. PUFA:TFA polyunsaturated fatty acids to total fatty acid ratio, MUFA:TFA monounsaturated fatty acid to total fatty acid ratio, SFA:TFA saturated fatty acid to total fatty acid ratio.
Fig 2
Fig 2. Metabolite SD difference between GDM treatment groups compared to No-GDM women at time point 2, at time of OGTT (mean 27+5 weeks’).
Data points show the standard deviation (SD) difference between treatment group and No-GDM women. Positive differences compared to No-GDM are shown to the right, negative to the left. PUFA:TFA polyunsaturated fatty acids to total fatty acid ratio, MUFA:TFA monounsaturated fatty acid to total fatty acid ratio, SFA:TFA saturated fatty acid to total fatty acid ratio.
Fig 3
Fig 3. Metabolite SD difference between GDM treatment groups compared to No-GDM women at time point 3, following treatment (mean 34+6 weeks’).
Data points show the standard deviation (SD) difference between treatment group and No-GDM women. Positive differences compared to No-GDM are shown to the right, negative to the left. PUFA:TFA polyunsaturated fatty acids to total fatty acid ratio, MUFA:TFA monounsaturated fatty acid to total fatty acid ratio, SFA:TFA saturated fatty acid to total fatty acid ratio.
Fig 4
Fig 4. Total triglyceride measurements in diet treated, insulin treated and No-GDM women at 3 gestational time points across pregnancy.
time point 2 (mean 27+5 weeks’) was fasting. 95% CI, not adjusted. * p value <0.05.
Fig 5
Fig 5. Glucose measurements in diet treated, insulin treated, and No-GDM women at 3 gestational time points across pregnancy.
time point 2 (mean 27+5 weeks’) was fasting. 95% CI, not adjusted. * p value <0.05.
See this image and copyright information in PMC

References

    1. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002. 10.1056/NEJMoa0707943 - DOI - PubMed
    1. Powe CE, Allard C, Battista M-C, Doyon M, Bouchard L, Ecker JL, et al. Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus. Diabetes Care. 2016;39:1052–5. 10.2337/dc15-2672 - DOI - PMC - PubMed
    1. Catalano PM. Obesity, insulin resistance, and pregnancy outcome. Reproduction. 2010;140(3):365–71. 10.1530/REP-10-0088 - DOI - PMC - PubMed
    1. Kautzky-Willer A, Prager R, Waldhausl W, Pacini G, Thomaseth K, Wagner OF, et al. Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care. 1997;20(11):1717–23. 10.2337/diacare.20.11.1717 - DOI - PubMed
    1. Ward WK, Johnston CL, Beard JC, Benedetti TJ, Porte D Jr. Abnormalities of islet B-cell function, insulin action, and fat distribution in women with histories of gestational diabetes: relationship to obesity. J Clin Endocrinol Metab. 1985;61(6):1039–45. 10.1210/jcem-61-6-1039 - DOI - PubMed

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