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

초록

Aims The expression of TGFbeta-inducible gene h3(betaig-h3) has been used to assess the biological activity of TGFbeta in the kidney. In this study, we investigated whether the urinary concentration of betaig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of betaig-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 betaig-h3 were measured by enzyme-linked immunosorbent assay. Results (i) Urinary excretion of betaig-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 betaig-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 betaig-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 betaig-h3 in diabetic patients (r=0.383, P=0.006). (iii) In diabetic patients, urinary betaig-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 HbA(1c) (cholesterol: r=0.169, P=0.03, HbA(1c); r=0.387, P=0.044). Logistic regression analyses showed that urinary betaig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients. Conclusions Longitudinal monitoring of urinary betaig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and betaig-h3 could be a sensitive marker of diabetic kidney disease progression.

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