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

Toshiko Takao, Hiroyuki Yanagisawa, Machi Suka, Yoko Yoshida, Yukiko Onishi, Tazu Tahara, Takako Kikuchi, Akifumi Kushiyama, Motonobu Anai, Kazuyuki Takahashi, Sayaka Wakabayashi Sugawa, Hiroki Yamazaki, Shoji Kawazu, Yasuhiko Iwamoto, Mitsuhiko Noda, Masato Kasuga

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of Diabetes Investigation
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Copper/zinc ratio
  • Diabetic kidney disease
  • Soluble tumor necrosis factor-α receptor 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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