Short Communication Association between irisin and homocysteine in euglycemic and diabetic subjects Rafael Alis a,b , Fabian Sanchis-Gomar c,d , Helios Pareja-Galeano c,d , Antonio Hernández-Mijares d,e,f,g , Marco Romagnoli a,h , Víctor M. Víctor c,d,e,f , Milagros Rocha d,e,f, ⁎ a Research University Institute “Dr. Viña Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain b Faculty of Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain c Department of Physiology, Faculty of Medicine, University of Valencia, Spain d Institute of Health Research INCLIVA, Valencia, Spain e Service of Endocrinology, University Hospital Dr. Peset. Valencia, Spain f Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Valencia, Spain g Department of Medicine, Faculty of Medicine, University of Valencia, Spain h Department of Physical Education and Sports, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain abstract article info Article history: Received 16 July 2014 Received in revised form 23 August 2014 Accepted 25 August 2014 Available online 3 September 2014 Keywords: Irisin Homocysteine Cardiovascular risk factors Nicotinamide Myokine Objectives: The aim of study was to explore whether a relationship exists between homocysteine and irisin in type 2 diabetes (T2D) patients—a population with a high risk of developing cardiovascular disease—and euglycemic controls. Design and methods: 69 T2D patients and 75 control subjects (adjusted by body mass index (BMI)) were included in the study. Irisin and homocysteine concentrations and anthropometric and biochemical variables were determined. Results: Levels of homocysteine were significantly higher (11.0 ± 3.0 vs 12.4 ± 4.2 μmol/l) and levels of irisin were lower (279 ± 58 vs 263 ± 38 ng/ml) in T2D patients. When both T2D and controls were considered, irisin was found to correlate only with homocysteine (r = -0.215; p = 0.011). Moreover, a decreasing trend in irisin levels was observed according to homocysteine tertile (p = 0.034). Conclusions: Our results provide evidence of an association between irisin and homocysteine, which may be due to nicotinamide metabolism. The clinical significance of this relationship is unclear, but our findings may prompt further mechanistic research to investigate the role played by irisin in vascular disorders. © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Introduction Irisin, a newly identified peptidic myokine, is secreted in response to peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α) activation [1]. It promotes a brown-phenotype switching in white adipose tissue, which increases energy expenditure [1]. Its utility in monitoring for obesity, diabetes and other energy-imbalance related disorders has been explored [2], leading to great expectations surround- ing “irisinemia” as new concept in the prediction of metabolic disorders [3]. Moreover, irisin is reported to be involved in insulin resistance in both humans [4] and animal models [1]. However, contradictory results have been published in several studies in humans, and there is an ongo- ing debate about the physiological significance of irisin. Homocysteine is a highly reactive sulfur-containing amino acid and an emerging risk factor for cardiovascular diseases. Elevated homocysteine levels have been related to an increased risk of suffering atherothrombotic vascular disease, myocardial infarction and stroke [5]. Recently, irisin has been suggested as a possible biomarker in acute myocardial infarction [6], and so we set out to explore whether a relationship exists between homo- cysteine and irisin levels in both T2D patients—a population with a high risk of developing cardiovascular disease—and euglycemic controls. Design and methods Seventy-five T2D patients and 69 euglycemic volunteers (adjusted by BMI) were recruited at the Endocrinology Service of the Dr. Peset University Hospital. T2D was diagnosed when a patient fulfilled the criteria of the American Diabetes Association [7]. The inclusion criteria for all subjects were: age range of 18–75 years, and normal kidney func- tion, liver function, heart function, protein status and hematological profile. Exclusion criteria were type 1 diabetes, malignant neoplasm, triglycerides (TG) N 400 mg/dl and insulin treatment. The study was conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures involving human subjects were approved Clinical Biochemistry 47 (2014) 333–335 ⁎ Corresponding author at: University Hospital Doctor Peset, Endocrinology Service, Avda. Gaspar Aguilar 90, 46017 Valencia, Spain. E-mail address: milagros.rocha@uv.es (M. Rocha). http://dx.doi.org/10.1016/j.clinbiochem.2014.08.017 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem