Objective: Transforming growth factor (TGF)-beta1 is an important mediator in the pathogenesis of diabetic nephropathy. Urinary TGF-beta1 reflects TGF-beta1 production in the kidney, and alpha1-microglobulin tubular dysfunction. These 2 markers were studied in the early phases of type 1 diabetes.
Research design and methods: There were 113 type 1 diabetic children and adolescents (mean +/- SD: age 14.1 +/- 2.9 years, and diabetes duration 7.4 +/- 2.9 years, HbA1c 9.3 +/- 1.5%) and 39 healthy subjects (age 13.8 +/- 2.8 years) who participated in the study. Of the diabetic patients, 105 were normoalbuminuric (2-3 consecutive overnight urinary albumin excretion rates [AERs] <20 microg/min) and 8 had microalbuminuria (at least 2 AERs 20-200 microg/min). Overnight urinary TGF-beta1 and alpha1-microglobulin levels were measured and the results expressed as the ratio to urinary creatinine concentration.
Results: Data are medians (range). Diabetic patients had higher urinary TGF-beta1 levels than those of control subjects: 0.9 ng/mg (0.05-122.3) vs. 0.3 ng/mg (0.05-2.2) creatinine, respectively (P = 0.003). Urinary TGF-beta1 levels correlated with urinary glucose (r = 0.2, P = 0.03) and alpha1-microglobulin (r = 0.2, P = 0.02) levels, but not with HbA1c, AER, age, or duration of diabetes. In 43 patients with urinary TGF-beta1 above the control levels, urinary TGF-beta1 levels correlated with urinary glucose (r = 0.6, P < 0.001) and alpha1-microglobulin (r = 0.6, P < 0.001) levels. Diabetic patients had higher urinary alpha1-microglobulin levels than those of control subjects: 4.8 microg/mg (0.6-48.8) vs. 2.7 microg/mg (0.8-11.6) creatinine, respectively (P < 0.001). Alpha1-microglobulin levels correlated with AER (r = 0.2, P = 0.02), HbA1c (r = 0.3, P = 0.001), urinary glucose (r = 0.5, P < 0.001), and urinary TGF-beta1 levels.
Conclusions: An early rise in urinary TGF-beta1 levels was observed in young type 1 diabetic patients. Urinary TGF-beta1 is associated with 2 interrelated tubular markers, alpha1-microglobulin and urinary glucose.