Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study

• Published in: Journal of diabetes investigation Vol. 13; no. 2; pp. 299 - 307
• Main Authors: Takao, Toshiko, Yanagisawa, Hiroyuki, Suka, Machi, Yoshida, Yoko, Onishi, Yukiko, Tahara, Tazu, Kikuchi, Takako, Kushiyama, Akifumi, Anai, Motonobu, Takahashi, Kazuyuki, Wakabayashi Sugawa, Sayaka, Yamazaki, Hiroki, Kawazu, Shoji, Iwamoto, Yasuhiko, Noda, Mitsuhiko, Kasuga, Masato
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.02.2022; John Wiley and Sons Inc; Wiley
• Subjects: Alcohol use; Biomarkers; Body mass index; Copper; Copper/zinc ratio; Creatinine; Cross-Sectional Studies; Cystatin C; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Diabetic kidney disease; Diabetic Nephropathies - complications; Diabetic Nephropathies - epidemiology; Diabetic nephropathy; Fasting; Glomerular filtration rate; Humans; Inflammation; Insulin; Kidney diseases; Original; Outpatient care facilities; Oxidative stress; Patients; Regression analysis; Soluble tumor necrosis factor‐α receptor 1; Tumor necrosis factor-TNF; Womens health; Zinc; Japan; Soluble tumor necrosis factor-α receptor 1; Copper/zinc ratio; Diabetic kidney disease
• ISSN: 2040-1116; 2040-1124; 2040-1124
• DOI: 10.1111/jdi.13659

Aims/Introduction We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. Materials and Methods A cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of < 60 mL/min/1.73 m2. Areas under the curves (AUCs), cutoff values, and thresholds for detecting DKD were determined for the Cu/Zn ratio, soluble tumor necrosis factor‐α receptor 1 (sTNFαR1), and high‐sensitivity C‐reactive protein (hsCRP). Patients were categorized by each cutoff value of sTNFαR1 and the Cu/Zn ratio. Odds ratios (ORs) and biological interactions for the prevalence of DKD were determined. Results DKD was identified in 220 patients. AUC/optimal cutoff values were 0.777/1300 pg/mL for sTNFαR1, 0.603/1.1648 for the Cu/Zn ratio, and 0.582/305 ng/mL for hsCRP. The ORs for DKD were higher, but not significantly, in the sTNFαR1 < 1300 and Cu/Zn ≥ 1.1648 group, significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P < 0.0001), and further synergistically elevated in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group (P < 0.0001) compared with the sTNFαR1 < 1300 and Cu/Zn < 1.1648 group after multivariable adjustment. Levels of sTNFαR1 were significantly higher in the sTNFαR1 ≥ 1300 and Cu/Zn ≥ 1.1648 group than in the sTNFαR1 ≥ 1300 and Cu/Zn < 1.1648 group (P = 0.0006). Conclusions Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes. Under an inflammatory initiation signal of elevated serum sTNFαR1 levels, an increase in the Cu/Zn ratio may further exacerbate inflammation and is synergistically associated with a high prevalence of DKD in patients with type 2 diabetes.