ARTÍCULO

Plasma acylcarnitines and risk of type 2 diabetes in a Mediterranean population at high cardiovascular risk

Autores: Guasch-Ferre, M. (Autor de correspondencia); Ruiz-Canela López, Miguel; Li, J. ; Zheng, Y.; Bullo, M.; Wang, D. D.; Toledo Atucha, Estefanía Ainhoa; Clish, C.; Corella, D.; Estruch, R. ; Ros, E. ; Fito, M.; Aros, F.; Fiol, M. ; Lapetra, J. ; Serra-Majem, L. ; Liang, L. M.; Papandreou, C.; Dennis, C.; Martínez González, Miguel Ángel; Hu, F. B.; Salas-Salvado, J.
Título de la revista: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN: 0021-972X
Volumen: 104
Número: 5
Páginas: 1508 - 1519
Fecha de publicación: 2019
Lugar: WOS
Resumen:
Context: The potential associations between acylcarnitine profiles and incidence of type 2 diabetes (T2D) and whether acylcarnitines can be used to improve diabetes prediction remain unclear. Objective: To evaluate the associations between baseline and 1-year changes in acylcarnitines and their diabetes predictive ability beyond traditional risk factors. Design, Setting, and Participants: We designed a case-cohort study within the PREDIMED Study including all incident cases of T2D (n = 251) and 694 randomly selected participants at baseline (follow-up, 3.8 years). Plasma acylcarnitines were measured using a targeted approach by liquid chromatography-tandem mass spectrometry. We tested the associations between baseline and 1-year changes in individual acylcarnitines and T2D risk using weighted Cox regression models. We used elastic net regressions to select acylcarnitines for T2D prediction and compute a weighted score using a cross-validation approach. Results: An acylcarnitine profile, especially including short-and long-chain acylcarnitines, was significantly associated with a higher risk of T2D independent of traditional risk factors. The relative risks of T2D per SD increment of the predictive model scores were 4.03 (95% CI, 3.00 to 5.42; P < 0.001) for the conventional model and 4.85 (95% CI, 3.65 to 6.45; P < 0.001) for the model including acylcarnitines, with a hazard ratio of 1.33 (95% CI, 1.08 to 1.63; P < 0.001) attributed to the acylcarnitines. Including the acylcarnitines into the model did not significantly improve the area under the receiver operator characteristic curve (0.86 to 0.88, P = 0.61). A 1-year increase in C4OH-carnitine was associated with higher risk of T2D [per SD increment, 1.44 (1.03 to 2.01)]. Conclusions: An acylcarnitine profile, mainly including short-and long-chain acylcarnitines, was significantly associated with higher T2D risk in participants at high cardiovascular risk. The inclusion of acylcarnitines into the model did not significantly improve the T2D prediction C-statistics beyond traditional risk factors, including fasting glucose.