Association of Serum Tsukushi Levels with Urinary Albumin-Creatinine Ratio in Type 2 Diabetes Patients

Objective: Tsukushi is a newly identified hepatokine. Recent studies have shown that it relates to diabetes, lipid metabolism and fibrosis, but there is currently no investigation about whether Tsukushi is associated with diabetic kidney disease. Therefore, this study aimed to investigate the relationship between Tsukushi and diabetic kidney disease by characterizing Tsukushi levels in healthy subjects and type 2 diabetes with urinary albumin-creatinine ratio.

Methods: Serum Tsukushi level was quantified by enzyme-linked immunosorbent assay in 167 normoalbuminuria, 80 microalbuminuria, and 31 macroalbuminuria patients with type 2 diabetes as compared with 53 healthy subjects. The correlation analysis was used to investigate the relationship between urinary albumin-creatinine ratio or Tsukushi level and other metabolic parameters. Multiple linear regression and logistic regression analysis were used to analyze the independent factors for urinary albumin-creatinine ratio and estimated glomerular filtration rate.

Results: The Tsukushi level in the macroalbuminuria group was significantly higher than that in the normoalbuminuria or the microalbuminuria group. Multiple linear regression showed that the significantly independent factors for UACR included high Tsukushi quartile, systolic blood pressure, creatinine, homeostasis model assessment of insulin resistance, low 2-h post-oral glucose tolerance test c-peptide and female. Logistic regression demonstrated that the odds ratio of Tsukushi for glomerular filtration rate ≤90(mL/min/1.73m²) was 1.636 (95% CI 1.091-2.452, P=0.017).

Conclusion: The circulating Tsukushi increased in type 2 diabetes patients with albuminuria and was associated with urinary albumin-creatinine ratio, implying that Tsukushi may be involved in the pathogenesis of diabetic kidney disease, which deserves future studies.