Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK | The Journal of Nutrition

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Abstract

Background

Gestational Diabetes Mellitus (GDM) is the most common global pregnancy complication; however, prevalence varies substantially between ethnicities with South Asians (SA) experiencing up to 3-times the risk of the disease compared to white Europeans (WEs). Factors driving this discrepancy are unclear, although the metabolome is of great interest as GDM is known to be characterised by metabolic dysregulation.

Objectives

This primary aim was to characterise and compare the metabolic profiles of GDM in SA and WE women (at < 28 weeks’ gestation) from the Born in Bradford (BIB) prospective birth cohort in the UK.

Methods

146 fasting serum metabolites, from 2668 pregnant WE and 2671 pregnant South Asian (SA) women (average BMI 26.2 kg/m2, average age 27.3 years) were analysed using partial least squares discriminatory analyses to characterise GDM status. Linear associations between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2-hour post glucose) were also examined.

Results

Seven metabolites associated with GDM status in both ethnicities (variable importance in projection (VIP) ≥1), while 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the metabolite values analysed in relation to dysglycemia, lactate, histidine, apolipoprotein A1, HDL cholesterol, HDL2 cholesterol associated with decreased glucose concentration, while DHA and the diameter of very low-density lipoprotein particles (nm) associated with increased glucose concertation in WE women; while in SAs albumin alone associated with decreased glucose concentration.

Conclusions

This study shows that the metabolic risk profile for GDM differs between WE and SA women enrolled in BiB the UK. This suggests that aetiology of the disease differs between ethnic groups and that ethnic-appropriate prevention strategies may be beneficial.

Notes

MZ is currently funded by the Wellcome Trust (217446/Z/19/Z). The Born in Bradford data reported here were supported by a Wellcome Trust infrastructure grant [101597] and the National Institute for Health Research ARC Yorkshire and Humber [NIHR200166]. Funding for the metabolomics analyses has been provided by the US National Institutes of Health [R01 DK10324], the European Research Council (ERC) under the European Union’s Seventh Framework Programme [FP7/2007-2013] / ERC grant agreement no 669545 and the MRC via the MRC Integrative Epidemiology Unit Programme [MC_UU_00011/6].

Data described in the manuscript will not be made available but can be requested through Born in Bradford (https://borninbradford.nhs.uk). Analytic code will be made available upon request pending approval by the research team.

Abbreviation used: ApoA1, Apolipoprotein A1; BIB, Born in Bradford; DHA, Docosahexanoic Acid ; FAw3, Total Omega-3; FAw6, Total Omega-6; GDM, Gestational Diabetes Mellitus; GRM, Glycolysis Related Metabolites; HDL-C, High Density Lipoprotein Cholesterol; HD2L-C, High Density Lipoprotein-2 Cholesterol; IQR, Inter Quartile Range; LDL_D, Diameter of Low Density Lipoprotein; LPS, Lipoprotein Particle Size ; MSEP, Mean Square Error of Prediction ; MFA, Monounsaturated Fatty Acids; MW, Mann-Whitney; NHS, National Health Service; PCA, Principal Component Analyses; OGTT, Oral Glucose Tolerance Test; oPLSDA, Orthogonal Partial Least Squares Discriminatory Analyses; SAC-H, High Weight South Asian Cases; SANC-H, High Weight South Asian Non-Cases; SAC-N, Healthy Weight South Asian Cases; SANC-N, Healthy Weight South Asian Non-Cases; PLSDA, Partial Least Squares Discriminatory Analyses; RMSEE, Root Mean Square Error of Prediction; ROC, Receiver Operator Curve; SA, South Asian; SE, Standard Error; SFA, Saturated Fatty Acids; sPLSDA, Sparse Partial Least Squares Discriminatory Analyses; TCA, Tricarboxylic Acid Cycle ; VIP, Variable Importance in Projection; VLDL_D, Diameter of Very Low Density Lipoprotein; WEs, White Europeans; WEC-N, Healthy Weight White European Cases; WENC-N, Healthy Weight White European Non-Cases; WEC-H, High Weight White European Cases; WENC-H, High Weight White European Non-Cases,

Information Accepted manuscripts

Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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