Distinct Acylcarnitine Profiles in Women With Gestational Diabetes Mellitus, Pre-Gestational Diabetes Mellitus, and Normal Pregnancy Using Tandem Mass Spectrometry (Lc-Ms/Ms) Publisher



Majidi Z ; Hosseinkhani S ; Rahimi N ; Dehghanbanadaki H ; Golmakan MA ; Najjar N ; Nasliesfahani E ; Rezaeitavirani M ; Bandarian F ; Razi F
Source: Journal of Diabetes and Metabolic Disorders Published:2026

Abstract

Objectives: Gestational diabetes mellitus (GDM) is associated with increased maternal and fetal health risks, yet reliable predictive biomarkers remain poorly established. Acylcarnitines (ACs), key metabolites involved in fatty acid oxidation and energy metabolism, have been identified as potential early biomarkers for type 2 diabetes (T2D). However, their role in the metabolic alterations of GDM and pre-gestational diabetes mellitus (PGDM) during pregnancy remains largely unexplored. Methods: This was a case-control study involving 75 pregnant women categorized into three groups: normal pregnancy (n = 25), gestational diabetes mellitus (GDM, n = 28), and pre-gestational diabetes mellitus (PGDM, n = 22). Plasma samples were collected during the second trimester for PGDM and third trimester for GDM and normal pregnancies. A targeted metabolomic approach using ultra-high-pressure liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) was employed to quantify 30 acylcarnitine species. Univariate analyses were performed using ANOVA or Kruskal-Wallis tests, and principal component analysis (PCA) was applied to identify underlying metabolic patterns while controlling for collinearity. Results: Women with GDM showed significantly higher median levels of C5 (0.105 vs. 0.075 µmol/L, P < 0.001), C16-OH (0.005 vs. 0.004 µmol/L, P = 0.040), and C18:1-OH (0.009 vs. 0.007 µmol/L, P = 0.012) compared to controls. In PGDM, C3 (0.441 vs. 0.279 µmol/L, P = 0.018) and C5 (0.142 vs. 0.075 µmol/L, P < 0.001) were markedly elevated. Notably, C0, C3DC, C5, C10:1, and C14 differed significantly between GDM and PGDM (P < 0.05 for all). Principal component analysis revealed that PC2 (driven by short-chain ACs) was strongly associated with PGDM (adjusted OR = 1.48, 95% CI: 1.14–1.91, P = 0.006), while PC3 (hydroxylated long-chain ACs) was linked to GDM (adjusted OR = 1.21, 95% CI: 1.01–1.44, P = 0.046). Conclusions: Our findings reveal specific alterations in circulating acylcarnitine profiles in GDM and PGDM, highlighting their potential as novel metabolic indicators for screening, diagnosis, and management of diabetic pregnancies. Further studies are warranted to validate these metabolites as clinical biomarkers in larger cohorts. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2026.