Plasma acylcarnitines and risk of type 2 diabetes in a Mediterranean population at high cardiovascular risk. Academic Article uri icon

abstract

  • 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.

authors

  • Guasch-Ferré, Marta
  • Ruiz-Canela, Miguel
  • Li, Jun
  • Zheng, Yan
  • Bulló, Mònica
  • Wang, Dong D
  • Toledo, Estefanía
  • Clish, Clary
  • Corella, Dolores
  • Estruch, Ramon
  • Ros, Emilio
  • Fitó, Montserrat
  • Arós, Fernando
  • Fiol, Miquel
  • Lapetra, José
  • Serra-Majem, Lluís
  • Liang, Liming
  • Papandreou, Christopher
  • Dennis, Courtney
  • Martinez-Gonzalez, Miguel A
  • Hu, Frank B
  • Salas-Salvadó, Jordi

publication date

  • 2019