Differences in Pregnancy Metabolic Profiles and Their Determinants between White European and South Asian Women: Findings from the Born in Bradford Cohort

Abstract

There is widespread metabolic disruption in women upon becoming pregnant. South Asians (SA) compared to White Europeans (WE) have more fat mass and are more insulin-resistant at a given body mass index (BMI). Whether these are reflected in other gestational metabolomic differences is unclear. Our aim was to compare gestational metabolic profiles and their determinants between WE and SA women. We used data from a United Kingdom (UK) cohort to compare metabolic profiles and associations of maternal age, education, parity, height, BMI, tricep skinfold thickness, gestational diabetes (GD), pre-eclampsia, and gestational hypertension with 156 metabolic measurements in WE (n = 4072) and SA (n = 4702) women. Metabolic profiles, measured in fasting serum taken between 26–28 weeks gestation, were quantified by nuclear magnetic resonance. Distributions of most metabolic measures differed by ethnicity. WE women had higher levels of most lipoprotein subclasses, cholesterol, glycerides and phospholipids, monosaturated fatty acids, and creatinine but lower levels of glucose, linoleic acid, omega-6 and polyunsaturated fatty acids, and most amino acids. Higher BMI and having GD were associated with higher levels of several lipoprotein subclasses, triglycerides, and other metabolites, mostly with stronger associations in WEs. We have shown differences in gestational metabolic profiles between WE and SA women and demonstrated that associations of exposures with these metabolites differ by ethnicity.

Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity

“…The elevated amounts of several sizes of VLDL particles indicate that the women with GDM were carrying an increased metabolic burden in their late pregnancy, even though their GDM was treated according to the treatment guidelines. The increase in VLDL particles, also previously shown to associate with GDM (3,4,5,13,14), may reflect a similar interaction between lipid and glucose metabolism as occurs in type 2 diabetes (15). Nonetheless, an increase in levels of VLDLrelated particles is not an exclusive sign of diabetic status because it may also reflect pregnancy-induced metabolic alterations; i.e., higher levels have also been observed in pregnant women unaffected by GDM compared with nonpregnant women (16).…”

“…In 734 women with GDM from different geographical locations, similar associations between GDM and lipid profile including VLDL lipoproteins were reported (4). Furthermore, a positive association between GDM and GlycA was detected (4). By utilizing a metabolomics approach, we could obtain a comprehensive metabolic profile, and it was evident that women with GDM had an aberrant metabolic profile, which was even more pronounced in those women treated with medication.…”

“…The ketone bodies produced are used as a maternal energy source in place of glucose, which is mostly utilized by the fetus (25). Previous studies have also detected elevated levels in ketone bodies in pregnant women with high fasting glucose concentrations (26) and in association with GDM (3,4,27). The reason for the increased levels of both citrate and ketone bodies in women with GDM in our study is not clear.…”

“…Maternal overweight and obesity disturb the metabolic adaptation, and a loss of maternal metabolic plasticity increases the risk for pregnancy complications, the most common clinical condition being gestational diabetes (GDM) (2). There is evidence of differences in the metabolic profile of women with GDM in comparison with their healthy counterparts at the time of diagnosis (3,4) and even at early pregnancy, before the late GDM diagnoses (3,5). Further insights into the maternal metabolic profile related to GDM and its management, particularly medication, are needed when considering the likely adverse long-term health consequences of the metabolic aberrations to the mother and the child.…”

Predictive metabolomic profiling within a diverse population of pregnant women at low or high risk of gestational diabetes

“…This increased prevalence in South Asian women appears to be independent of BMI and the differences in adiposity between the two ethnicities (1) . Most surprisingly, although aetiologically similar to T2D, the metabolic traits that result in an elevated risk of GDM are poorly understood (2)(3)(4) . This study aimed to apply multivariate statistical methods to highlight common and unique metabolites and metabolic features that characterise and distinguish GDM risk in British Pakistani or white Caucasian women.…”