Original article Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus Afshin Samadi a , Selen Yilmaz Isikhan b, c , Alexey A. Tinkov d, e, f , Incilay Lay a, g , Monica Daniela Dos ¸a h , Anatoly V. Skalny e, f, i , Margarita G. Skalnaya e, f , Salvatore Chirumbolo j, k , Geir Bjørklund l, * a Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey b Department of Biostatistics, Faculty of Medicine, Hacettepe University, Ankara, Turkey c Vocational School of Social Sciences, Hacettepe University, Ankara, Turkey d Yaroslavl State University, Yaroslavl, Russia e Peoples' Friendship University of Russia (RUDN University), Moscow, Russia f IM Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia g Clinical Pathology Laboratory, Hacettepe University Hospitals, Ankara, Turkey h Department of Pharmacology, Faculty of Medicine, Ovidius University, Constanta, Romania i Federal Research Centre of Biological Systems and Agro-technologies of the Russian Academy of Sciences, Orenburg, Russia j Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy k CONEM Scientific Secretary, Verona, Italy l Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway article info Article history: Received 28 March 2019 Accepted 20 July 2019 Keywords: Diabetes mellitus Zinc Copper Oxysterol summary Background: The present study has the objective to assess the zinc (Zn), copper (Cu), and oxysterols plasma levels in type 1 (DM1) (n ¼ 26) and type 2 (DM2) (n ¼ 80) diabetes patients, as compared to healthy controls (n ¼ 71), in order to testify whether metal levels may have a significant impact on the association between oxysterols and diabetes. Methods: Plasma trace elements and plasma oxysterols were assessed using atomic absorption spec- trometry and LC-MS/MS, respectively. Lifestyle, smoking status, alcohol intake, and drug usage, as well as microvascular complications, were also monitored and reported. Results: The obtained data demonstrated that both DM1 and DM2 patients were characterized by significantly elevated HbA1c, FBG, TC, LDL-C, VLDL-C, and TG levels as compared to controls. Plasma Zn levels and Zn/Cu ratio in DM1 and DM2 patients were about 3- and 2-fold lower than controls. No significant differences in plasma Cu levels were reported. The 7-ketocholesterol (7-kchol) levels in DM1 and DM2 patients exceeded these values in healthy individuals by 2.5 and 5-fold, respectively. Similarly, cholestan-3b,5a,6b-triol (chol-triol) levels were more than 3- and 6-fold higher when compared to the respective values in non-diabetic controls. In regression models decreased plasma Zn and elevated oxysterol levels were significantly associated with HbA1c and fasting plasma glucose levels, after adjustment for anthropometric and clinical variables, as well as routine biochemical markers. Conclusions: Plasma Zn concentration is inversely associated with both 7-kchol and chol-triol levels. Assessment of Zn and oxysterol levels may be used both for risk assessment and as targets for the treatment of diabetes mellitus. © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. 1. Introduction Diabetes mellitus (DM) is to date a relevant concern of the public health worldwide and its expansion and exacerbation among the global population is still due to contributing factors like urbanization and environmental pollution, aging, obesity, and sedentary lifestyle [1e4]. In 2016 the prevalence of diabetes was * Corresponding author. Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway. E-mail address: bjorklund@conem.org (G. Bjørklund). Contents lists available at ScienceDirect Clinical Nutrition journal homepage: http://www.elsevier.com/locate/clnu https://doi.org/10.1016/j.clnu.2019.07.026 0261-5614/© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. Clinical Nutrition xxx (xxxx) xxx Please cite this article as: Samadi A et al., Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.07.026