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Harriett Fuller, Mark Iles, J Bernadette Moore, Michael Zulyniak
Background Women of South Asian descent are three times as likely to develop gestational diabetes mellitus (GDM) as white European (WE) mothers, independent of BMI status. This study aims to identify serum-metabolite drivers of GDM within WE and British Pakistani (PK) women from the Born in Bradford (BIB) cohort.
Methods 146 metabolites, including dietary-related lipoproteins, fatty acids, cholesterol and amino acids, were included. Partial least squares discriminatory analyses (PLSDA) and sparse PLSDA (sPLSDA) were used to distinguish ethnic-specific metabolite signatures of GDM in 2668 WEs and 2671 PK pregnant women (gestational age ≤196 days) in the BIB cohort. The impact of BMI on the metabolome and GDM risk, along with other known GDM risk factors (age, parity, multiple pregnancy and smoking status), was also examined.
Results Seven metabolites across a panel of metabolic processes (fatty acids, glycolytic, and cholesterol metabolism) were found to be predictive of GDM in both ethnicities, with fatty acids appearing to be more important drivers of GDM within WEs. Additionally, 6 metabolites were predictive of GDM solely within WEs, whilst no distinct metabolite associations were observed in PKs. Following the stratification of women by their BMI, case-status and ethnicity, a distinct metabolite profile was identified within normal-weight PK cases when compared to all other cases, characterised by a panel of amino acids and cholesterols, and glycolytic and unsaturated fatty acid metabolites.
Conclusion Serum-metabolite profiles differ by ethnicity and GDM status, largely driven by differences in fatty acid and cholesterol metabolite levels. However, in normal-weight PK women, a broad range of metabolic processes are uniquely altered and offer insight into the elevated risk of GDM observed in this otherwise healthy population. Future investigations into the determinants of these differences in metabolite profiles may shed light on the aetiology of elevated GDM risk in healthy PK women and direct the development of more efficacious intervention strategies.