Plasma acylcarnitines and risk of type 2 diabetes in a mediterranean population at high cardiovascular risk
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Plasma acylcarnitines and risk of type 2 diabetes in a mediterranean population at high cardiovascular risk. / 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, Llúis; Liang, Liming; Papandreou, Christopher; Dennis, Courtney; Martínez-González, Miguel A.; Hu, Frank B.; Salas-Salvadó, Jordi.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 104, No. 5, 2019, p. 1508-1519.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma acylcarnitines and risk of type 2 diabetes in a mediterranean population at high cardiovascular risk
AU - Guasch-Ferré, Marta
AU - Ruiz-Canela, Miguel
AU - Li, Jun
AU - Zheng, Yan
AU - Bulló, Mònica
AU - Wang, Dong D.
AU - Toledo, Estefanía
AU - Clish, Clary
AU - Corella, Dolores
AU - Estruch, Ramon
AU - Ros, Emilio
AU - Fitó, Montserrat
AU - Arós, Fernando
AU - Fiol, Miquel
AU - Lapetra, José
AU - Serra-Majem, Llúis
AU - Liang, Liming
AU - Papandreou, Christopher
AU - Dennis, Courtney
AU - Martínez-González, Miguel A.
AU - Hu, Frank B.
AU - Salas-Salvadó, Jordi
N1 - Publisher Copyright: Copyright © 2019 Endocrine Society.
PY - 2019
Y1 - 2019
N2 - 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 C4OHcarnitine 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.
AB - 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 C4OHcarnitine 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.
U2 - 10.1210/jc.2018-01000
DO - 10.1210/jc.2018-01000
M3 - Journal article
C2 - 30423132
AN - SCOPUS:85060872838
VL - 104
SP - 1508
EP - 1519
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -
ID: 358089821