Contents lists available at ScienceDirect Journal of Trace Elements in Medicine and Biology journal homepage: www.elsevier.com/locate/jtemb Association between zinc nutritional status and glycemic control in individuals with well-controlled type-2 diabetes Alvaro Perez a , Pamela Rojas a , Fernando Carrasco a , Karen Basfi-fer a , Francisco Perez-Bravo a , Juana Codoceo a , Jorge Inostroza a , Jose E. Galgani b,c , L. Anne Gilmore d , Manuel Ruz a, ⁎ a Department of Nutrition, Faculty of Medicine, University of Chile, Santiago, Chile b Department of Nutrition, Diabetes and Metabolism, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile c Department of Health Sciences-Nutrition and Dietetics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile d Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA ARTICLE INFO Keywords: Diabetes Zinc Insulin resistance Humans ABSTRACT Background/objective: Interest in healthy properties of food and nutrients as co-adjuvant in type-2 diabetes therapy has increased in recent years. Zinc supplementation trials have shown improvements in glycemic control in these patients, although it seems dependent on zinc status of the individuals. The objective of this study was to evaluate the relationship between zinc nutritional status and glucose homeostasis in patients with type-2 dia- betes. Subjects/methods: Eighty patients with well controlled type-2 diabetes were recruited and clinical, anthropo- metric and dietary evaluations were performed. One week after, insulin sensitivity and beta cell function were assessed by a modified Frequently Sampled Intravenous Glucose Tolerance Test. Zinc status was assessed by plasma zinc and the size of rapidly Exchangeable Zinc Pool (EZP); zinc intake was also determined. Glucagon concentration was evaluated in a subsample of 36 patients. Results: Patients presented a normal zinc status although zinc intake was lower than recommended. Overall, no associations were observed between zinc status and glycemic control markers. Nevertheless, positive correlations were observed between EZP and fasting insulin concentration (ρ = 0.393, p = 0.021) and HOMA-IR (ρ = 0.386, p = 0.024) in women, and between plasma zinc concentration and HbA1c (ρ = 0.342, p = 0.020) in men. Conclusions: No significant associations were found between zinc status and glycemic control parameters in patients with well-controlled type 2 diabetes and normal zinc status, although low-degree gender-dependent associations were observed. Further research is required to assess the role of zinc status in zinc deficient patients. 1. Introduction Type-2 diabetes (T2DM) is a chronic metabolic disease produced by the inability of pancreas to increase insulin secretion to compensate its reduced activity in insulin-sensitive tissues, giving as a result a condi- tion of persistent hyperglycemia, among other features [1]. It is asso- ciated with several comorbidities including retinopathy, nephropathy, neuropathy and increased risk of cardio- and cerebro-vascular diseases [1], which increases risk of death up to four times [2]. Treatment of T2DM includes changes in lifestyle as well as phar- macological support. Nutrition therapy is essential to achieve adequate weight reduction and improvement in metabolic parameters [3]. In addition to nutritional counseling, interest in health-promoting prop- erties of foods and nutrients, including zinc, as potential co-adjuvant in treatment for T2DM has markedly increased in recent years [4,5]. Zinc is an essential micronutrient greatly concentrated in endocrine pancreas [6], where it participates in several functions related with blood glucose homeostasis. Adequate or increased amounts of zinc in pancreas may be beneficial in T2DM, favoring assembly of insulin hexamer [7,8] and regulation of insulin and glucagon secretion as well as hepatic insulin clearance [9–11]. In addition, zinc presents insulin- mimetic properties that enhance the activity of key components of in- sulin signaling pathway [12,13], modulates cytokines expression re- lated with chronic low-grade inflammatory state of T2DM [13,14], and contributes to decrease the oxidative stress generated in T2DM as a consequence of glucose surplus [15]. Several studies have assessed the effect of zinc supplementation in blood glucose control. Two meta-analyses showed modest positive ef- fects of supplemental zinc in glucose homeostasis both in healthy in- dividuals and subjects with diabetes [16,17]. In a recent review https://doi.org/10.1016/j.jtemb.2018.03.019 Received 26 October 2017; Received in revised form 8 March 2018; Accepted 22 March 2018 ⁎ Corresponding author at: Department of Nutrition, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile. E-mail address: mruz@med.uchile.cl (M. Ruz). Journal of Trace Elements in Medicine and Biology 50 (2018) 560–565 0946-672X/ © 2018 Elsevier GmbH. All rights reserved. T