The mediating role of inflammation-related indicators in the association of remnant cholesterol with gestational diabetes mellitus

TL;DR

Higher cholesterol levels in early pregnancy are linked to a greater risk of gestational diabetes, with inflammation markers playing a partial role in this connection.

Contribution

This study identifies remnant cholesterol as an early predictor of gestational diabetes and shows its association is partially mediated by inflammation-related indicators.

Findings

Higher remnant cholesterol levels in early pregnancy are associated with increased gestational diabetes risk.

Leukocytes and neutrophils partially mediate the relationship between remnant cholesterol and gestational diabetes.

The association remains significant even when other cholesterol levels are within normal ranges.

Abstract

Gestational diabetes mellitus (GDM) is a common complication during pregnancy, posing threats to both maternal and infant health. We aimed to investigate the association of remnant cholesterol (RC) and GDM during the first trimester of pregnancy through a prospective cohort study, and to explore the mediating effects of inflammation-related indicators.

We analysed data including 13 446 pregnant women and employed a generalised linear model to estimate the relative risk (RR) and 95% confidence intervals (CI) for the associations between RC level and GDM. We used the restricted cubic spline analyses to reflect the dose-response relationship. We made mediation analyses to explore the mediating effects of inflammation-related indicators on the relationship between RC level and risk of GDM.

The overall incidence of GDM was 22.3%, and this incidence increased across the RC quartiles, reaching 25.7% for the highest quartile of RC levels. There was a linear upward trend in the risk of GDM with increasing RC levels during the first trimester of pregnancy (P < 0.001 and for nonlinearity P = 0.124). Compared to the lowest RC quartile, higher RC quartiles were linked with an increased risk of GDM, with quartile two RR = 1.20 (95% CI = 1.07–1.36), quartile three RR = 1.24 (95% CI = 1.11–1.40), and quartile four RR = 1.48 (95% CI = 1.32–1.67), in the crude model. This positive association persisted even when total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were within normal ranges, and it was consistent across groups stratified by maternal advanced age, occupation, gravidity, parity, pre-pregnancy body mass index, and hypertensive disorder of pregnancy. Moreover, inflammation-related indicators, including leukocytes and neutrophils, partially mediated these associations, accounting for 4.89% and 6.60% of the mediation proportion, respectively.

Higher serum RC levels in early pregnancy were positively associated with an increased risk of developing GDM. Leukocytes and neutrophils partially mediated these associations. RC may serve as an early predictor of GDM, and monitoring RC may help optimise GDM prevention.

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