Urinary concentration of transforming growth factor-β-inducible gene-h3(βig-h3) in patients with Type 2 diabetes mellitus


Nan Hee Kim, Department of Internal Medicine, Division of Endocrinology, Korea University Hospital, 516 Kojan-Dong, Ansan City, Kyungki-Do, 425–020, Korea. E-mail: nhkim@kumc.or.kr


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.