Lipid profile and cardiac biomarkers in mid-pregnancy among women with gestational diabetes: insights from the EpiDG study

Women with gestational diabetes mellitus (GDM) are at increased risk of future cardiovascular disease, but whether this risk is accompanied by early alterations in lipid-related and cardiovascular biomarkers during pregnancy remains unclear. We investigated the cardiometabolic biomarker profile associated with GDM during mid-pregnancy. In this observational study within the prospective EpiDG cohort, 295 pregnant women with a positive 50-g O’Sullivan screening test underwent a diagnostic 100-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. Of these, 111 met the National Diabetes Data Group (NDDG) diagnostic criteria for GDM and 184 did not meet these criteria and served as screen-positive controls. Conventional lipid parameters, apolipoproteins, lipoprotein(a), high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed. Compared with controls, women with GDM had lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) concentrations and higher triglyceride levels, triglyceride-to-HDL cholesterol, and triglyceride-to-ApoA-I ratios. ApoA-I (adjusted odds ratio [OR] per 10 mg/dL 0.88, 95% confidence interval [CI] 0.80–0.95; p = 0.003) and triglycerides (adjusted OR per 10 mg/dL 1.06, 95% CI 1.01–1.12; p = 0.018) were independently associated with GDM. Their inclusion was associated with higher in-sample discrimination in an exploratory ROC analysis (area under the curve [AUC] 0.703 vs. 0.646; nominal p = 0.036). The proportions of women with quantifiable hs-cTnI and NT-proBNP concentrations did not differ between groups. GDM was associated with a less favourable lipid-metabolic profile during mid-pregnancy, characterised by lower HDL-C and ApoA-I concentrations, higher triglyceride levels, and increased triglyceride-derived lipid ratios. ApoA-I and triglyceride concentrations remained independently associated with GDM status after multivariable adjustment, supporting lipoprotein metabolism as a component of the cardiometabolic phenotype accompanying GDM. Women with gestational diabetes showed a less favourable mid-pregnancy lipid profile, with lower HDL-C and ApoA-I and higher TG concentrations. ApoA-I and TG were independently associated with gestational diabetes after adjustment for established clinical risk factors. Adding both biomarkers to a clinical model improved in-sample discrimination, a finding that requires external validation. In an exploratory analysis, the highest hs-cTnI concentrations were concentrated among women with gestational diabetes, whereas the proportions with quantifiable hs-cTnI and NT-proBNP concentrations were similar between groups. Longitudinal studies are needed to establish whether these mid-pregnancy alterations translate into future cardiovascular risk.