title: Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A Cross-sectional Study.
abstract: BACKGROUND
  Zinc (Zn) and copper (Cu) may play a pivotal role in the pathogenesis of diabetes and diabetic complications by mediating oxidative stress. Both Zn deficiency and excess of Cu are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to investigate the relationships between serum Zn/Cu ratio and glycemic status, renal function, and metabolic parameters in patients with and without type 2 diabetes.
  
  
  METHODS
  We conducted a cross-sectional study on 355 subjects (149 type 2 diabetic and 206 non-diabetic) in whom serum Zn and Cu levels were measured at the same time. Associations between serum Zn/Cu ratio and clinical data were evaluated using multiple regression analysis. We also evaluated associations between serum Zn/Cu ratio and the prevalence of type 2 diabetes and glycemic control by multivariate logistic regression analysis.
  
  
  RESULTS
  Serum Zn/Cu ratio was positively associated with estimated glomerular filtration rate after adjustment for body mass index (BMI) (β = 0.137,p= 0.014). Plasma B-type natriuretic peptide levels were negatively associated with serum Zn/Cu ratio after adjustment for age, sex, and BMI (β = -0.258,p= 0.032). In patients with type 2 diabetes, serum Zn/Cu ratio was negatively associated with plasma HbA1c levels after adjustment for age, sex, and BMI (β = -0.239,p= 0.003). In addition, multivariate logistic regression analysis revealed that the highest quartile of serum Zn/Cu ratio was associated with a reduced risk of poor (HbA1c ≥ 7%) glycemic control (odds ratio = 0.382; 95% confidence interval, 0.165-0.884;p= 0.025) in patients with type 2 diabetes.
  
  
  CONCLUSIONS
  Serum Zn/Cu ratio was favorably associated with renal function in all subjects and glycemic control in patients with type 2 diabetes. The Zn/Cu ratio, in addition to the individual serum levels of trace elements, is important for metabolism in humans.
authors.affiliation: Department of Internal Medicine, National Center for Global Health and Medicine, Kohnodai Hospital , Chiba , Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hamasaki
authors.affiliation: Department of Radiology, Chiba University Hospital , Chiba , Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: Department of Internal Medicine, National Center for Global Health and Medicine, Kohnodai Hospital , Chiba , Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Yanai
keywords: B-type natriuretic peptide; copper; eGFR; type 2 diabetes; zinc