Among individuals at high risk for cardiovascular disease, a panel of acylcarnitines, especially those with short and long chains, was significantly associated with the incidence of type 2 diabetes (T2D), according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Plasma acylcarnitines are involved in key metabolic pathways associated with insulin resistance and T2D, and high concentrations of short- and long-chain acylcarnitines have been associated with obesity, insulin resistance, and T2D. However, prospective studies investigating the associations between acylcarnitine profiles and T2D incidence have been limited and have produced inconsistent results. In the current study, researchers evaluated the associations between baseline and 1-year changes in acylcarnitines and their ability to predict diabetes beyond the traditional risk factors. 

They designed a nested case control study within the framework of the PREDIMED study, a multicenter randomized trial that enrolled individuals at high risk for cardiovascular disease into 3 diet groups. The current study evaluated 892 participants without diabetes at baseline, including 251 incident cases of T2D and 641 participants without T2D who were randomly selected as controls.

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At a median follow-up of 3.8 years, researchers found that the relative risk for T2D per each standard deviation increment of the predictive model scores was 4.03 (95% CI, 3.00-5.42; P <.001) for the model that included only traditional risk factors and 4.85 (95% CI, 3.65-6.45; P <.001) for the model that included acylcarnitines (hazard ratio, 1.33; 95% CI, 1.08-1.63; P <.001). Several short-chain acylcarnitines including C2, C3, C4OH, C5, and C6 were associated with increased risk for T2D, and long-chain carnitines C18, C18:1, and C20 were linked with a lower risk for T2D.

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The investigators caution that these findings should be “interpreted in the context of several limitations,” one being that generalizability of the results may be limited in other populations given the cohort of only Mediterranean participants.

“Second, although we have adjusted for many potential confounders, residual confounding cannot be completely ruled out,” they added.

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Guasch-Ferré M, Ruiz-Canela M, Li J, et al. Plasma acylcarnitines and risk of type 2 diabetes in a Mediterranean population at high cardiovascular risk [published online November 13, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01000