Urinary concentration of transforming growth factor-β-inducible gene-h3(βig-h3) in patients with Type 2 diabetes mellitus
Article first published online: 2 DEC 2004
Volume 22, Issue 1, pages 14–20, January 2005
How to Cite
Cha, D. R., Kim, I. S., Kang, Y. S., Han, S. Y., Han, K. H., Shin, C., Ji, Y. H. and Kim, N. H. (2005), Urinary concentration of transforming growth factor-β-inducible gene-h3(βig-h3) in patients with Type 2 diabetes mellitus. Diabetic Medicine, 22: 14–20. doi: 10.1111/j.1464-5491.2004.01295.x
- Issue published online: 2 DEC 2004
- Article first published online: 2 DEC 2004
- Accepted 10 November 2003
- diabetic nephropathy;
- TGFβ-inducible gene h3(βig-h3)
Aims The expression of TGFβ-inducible gene h3(βig-h3) has been used to assess the biological activity of TGFβ in the kidney. In this study, we investigated whether the urinary concentration of βig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of βig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients.
Methods Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (n = 443), a non-diabetic healthy control group with microalbuminuria (n = 85), a normoalbuminuric diabetic group (n = 198), a microalbuminuric diabetic group (n = 155) and an overt proteinuria group (n = 126). Urinary levels of βig-h3 were measured by enzyme-linked immunosorbent assay.
Results (i) Urinary excretion of βig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 ± 8.84 vs. 18.67 ± 6.56, P = 0.03). In diabetic patients, urinary βig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 ± 8.84 vs. 34.06 ± 24.55 vs. 169.63 ± 57.33, P < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary βig-h3 (healthy control; r = 0.137, P = 0.019, diabetic patients; r = 0.604, P < 0.001). ACR was also found to be significantly related with urinary βig-h3 in diabetic patients (r = 0.383, P = 0.006). (iii) In diabetic patients, urinary βig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: r = 0.436, P = 0.024; diastolic blood pressure, r = 0.365, P = 0.042), total cholesterol and HbA1c (cholesterol: r = 0.169, P = 0.03, HbA1c; r = 0.387, P = 0.044). Logistic regression analyses showed that urinary βig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients.
Conclusions Longitudinal monitoring of urinary βig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and βig-h3 could be a sensitive marker of diabetic kidney disease progression.