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Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk

AuthorsGuasch‐Ferré, Marta; Ruiz-Canela, Miguel; Li, Jun ; Zheng, Yan; Bulló, Mònica; Wang, Dong D.; Toledo, Estefania; Clish, Clary B.; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol, Miquel; Lapetra, Jose; Serra-Majem, Lluis; Liang, Liming; Papandreou, Christopher; Dennis, Courtney; Martínez-González, Miguel Ángel; Hu, Frank B.; Salas-Salvadó, Jordi
Issue DateMay-2019
PublisherOxford University Press
CitationJournal of Clinical Endocrinology and Metabolism 104(5): 1508-1519 (2019)
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.
Publisher version (URL)http://dx.doi.org/10.1210/jc.2018-01000
Identifiersdoi: 10.1210/jc.2018-01000
issn: 0021-972X
e-issn: 1945-7197
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