Acylcarnitines as markers of early cardiometabolic dysregulation in a population-based sample of apparently healthy adults
K K Maung, R Borreggine, H Gallart-Ayala, J Ivanisevic, P Marques-VidalAbstract
Background
Acylcarnitines (AC), intermediates of mitochondrial fatty acid oxidation, have been linked to metabolic dysregulation and adiposity; however, evidence in apparently healthy adults remains limited. We aimed to examine associations between circulating AC species and adiposity-related markers and systemic inflammation cross-sectionally, and with 10-year incidence of diabetes in a population-based cohort.
Methods
We analysed data from 1,977 apparently healthy participants in our city, Switzerland. Thirty AC species were quantified. Anthropometric markers included weight, body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and body roundness index (BRI). Inflammatory markers included high-sensitivity C-reactive protein (hs-CRP). Multivariable regression models adjusted for demographic and lifestyle confounders were used. Incident diabetes was defined as HbA1c ≥6.5% or initiation of glucose-lowering medication at follow-up. P-values were corrected using false discovery rate (FDR).
Results
Short-chain AC, particularly Propionyl- and Isovalerylcarnitine, together with free carnitine, showed the strongest positive associations with multiple adiposity markers after adjustment, with consistent patterns across BMI, waist circumference, WHtR and BRI. Medium- and long-chain AC displayed weaker or inconsistent associations. Associations with inflammatory markers were modest; only Adipoylcarnitine remained positively associated with hs-CRP after adjustment. Over 10 years, 35 participants developed diabetes. Nominal associations between selected short-chain AC and incident diabetes were observed but were attenuated after adjustment for adiposity and did not remain significant after FDR correction.
Conclusion
In apparently healthy adults, short-chain acylcarnitines are consistently associated with adiposity-related phenotypes, supporting their role as markers of early metabolic alterations. Prospective associations with diabetes appear modest and largely adiposity-driven.