Circulating and Urinary Transforming Growth Factor β1, Amadori Albumin, and Complications of Type 1 Diabetes

Abstract

OBJECTIVE—Transforming growth factor (TGF)-β1 is overexpressed in diabetes as a consequence of hyperglycemia and the creation of early glycated end products and may be responsible for the characteristic structural renal changes associated with diabetes. We sought to examine the role of both urinary and circulating TGF-β1 and its promoter Amadori albumin in the vascular complications of type 1 diabetes.

RESEARCH DESIGN AND METHODS—The present article reports on a nested case-control study from the EURODIAB Prospective Complications Study of Europeans with type 1 diabetes. Case subjects (n = 356) were all individuals with one or more complications of diabetes; control subjects (n = 185) were all individuals with no evidence of complications.

RESULTS—Urinary TGF-β1 and Amadori albumin were elevated in patients with micro- or macroalbuminuria. Standardized regression effects (SREs) for macroalbuminuria versus normoalbuminuria were 2.45 (95% CI 1.88–3.18, P = 0.0001 for urinary TGF-β1) and 1.67 (1.34–2.07, P = 0.001 for Amadori albumin). The SRE for urinary TGF-β1 remained statistically significant when adjusted for HbA_1c, Amadori albumin, and blood pressure. Circulating TGF-β1 was elevated in individuals with proliferative retinopathy compared with individuals without retinopathy (SRE 1.29 [1.07–1.550], P = 0.007). This result was attenuated to 1.16 (0.95–1.43, P = 0.2) in the multivariate model, largely because of HbA_1c.

CONCLUSIONS—Elevated levels of urinary TGF-β1 in macroalbuminuria were associated with elevations in Amadori albumin and HbA_1c and also in blood pressure. In contrast, only circulating TGF-β1 was related to proliferative retinopathy, and HbA_1c largely accounted for this. These findings may indicate novel pathways for understanding mechanisms and therapeutic interventions.