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Scientists discover the role of plasma acylcarnitines profile in early prediction of type 2 diabetes

Research teams led by Professor LIN Xu at the Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, by Professor WU Jiarui and Professor ZENG Rong at the Key Laboratory of Systems Biology, SIBS, Chinese Academy of Sciences reported that a panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors.

As a largely preventable disease, early prediction is the key to control the global epidemic trend of type 2 diabetes, which requires identification of novel biomarkers. With the rapid development of advanced metabolomic technology, omics-based biomarkers are expected to be used for earlier prediction of metabolic diseases.

The concept of “mitochondrial stress” induced by mitochondrial lipid overload and increased incomplete fatty acid oxidation (FAO) has been proposed to have an important impact on the pathogenesis of insulin resistance and diabetes. Carnitine is known to play a pivotal role in transporting long-chain fatty acids across the mitochondrial inner membrane for β-oxidation (Fig 1). As intermediates of carnitine metabolism, acylcarnitines were previously shown to reflect mild FAO dysregulation and “mitochondrial stress” by animal studies. Moreover, different profiles of acylcarnitines were detected comparing cases of obesity, insulin resistance, metabolic syndrome or diabetes with relevant controls. However, it remains to be evaluated whether acylcarnitines are able to identify high-risk individuals for future development of type 2 diabetes.

In this population-based prospective study, baseline plasma acylcarnitines were measured by liquid chromatography-tandem mass spectrometry in 2103 community-living Chinese aged 50-70 years from Beijing and Shanghai, and 34 free carnitine and acylcarnitines were detected. SUN Liang, LIANG Liming and GAO Xiangfu et al found that a panel of acylcanitines, especially with long-chain, was significantly associated with increased risk of type 2 diabetes, independent of conventional risk factors including body mass index (BMI), fasting glucose, glycohemoglobin (HbA1c) and family history of diabetes. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in full model compared with 0.73 in the conventional model (age, sex, region, residence, smoking, drinking, physical activity, family history of diabetes, BMI, fasting glucose, HbA1c and systolic blood pressure), suggesting potential utility of acylcarnitines as novel early predictors in diabetes risk assessment (Fig 2). To the best of our knowledge, the current study was the first study showing acylcarnitines, mainly involving mitochondrial lipid dysregulation, could effectively predict incident diabetes.

This study was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China and Chinese Academy of Sciences, etc.

The study, entitled “Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: Population-Based Study” was published online on July 7, 2016 on Diabetes Care.

The website for this article is: http://care.diabetesjournals.org/content/early/2016/07/06/dc16-0232

Fig 1 Carnitine and long chain fatty acids oxidation

Fig 2 The predictive value of acylcarnitines on incidence of type 2 diabetes
Image by Dr. Lin’s lab

Author contact
Lin Xu, Ph.D.
Professor and Principle Investigator
Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, CAS, 320 Yueyang Road, Shanghai, China 200031
Tel: 86-21-5492-0249
Fax: 86-21-5492-0247
Email: xlin@sibs.ac.cn

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