Acylcarnitines as early predictors of 10-year diabetes risk in a population-based apparently healthy cohort

Background Current diabetes risk scores often fail to detect early metabolic changes. Novel biomarkers capturing early metabolic dysregulation may improve early detection before overt hyperglycaemia. Acylcarnitines (AC), intermediates of mitochondrial fatty acid oxidation, may indicate early dysregulation in diabetes, but prospective evidence is limited. Purpose To investigate associations between circulating AC species and 10-year incidence of diabetes and prediabetes in healthy adults, and to investigate whether ACs improve the predictive performance of established diabetes risk scores. Methods We used data from 1796 apparently healthy adults in a population-based cohort. Incident diabetes was defined as HbA1c≥6.5% or initiation of glucose-lowering medication at follow-up; incident prediabetes as HbA1c 39–47 mmol/mol or fasting plasma glucose 5.6–6.9 mmol/L. Associations were analysed using bivariate and multivariate models, and predictive value was assessed by adding ACs individually to seven established risk scores. Results Over 10 years, 35 participants developed diabetes and 876 participants developed prediabetes. Higher baseline levels of C3:0, were associated with incidence diabetes whereas C4:0-OH, C5:0 and C5:1 were associated with incidence prediabetes in both bivariate and multivariate analyses. In predictive analyses, C3:0 and C5:0-DC remained independently associated with incident diabetes after adjustment for each established diabetes risk scores. Adding C5:0 to the risk scores improved discrimination (AUC ≈ 0.02), particularly for the Balkau, Swiss Diabetes Association and FINRISK scores. Conclusion(s) Specific AC species, particularly C3 and C5, predicted 10-year risk of both diabetes and prediabetes and modestly improved predictive performance beyond established risk scores, suggesting their potential as early metabolic markers.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.