Circulating and urinary transforming growth factor beta 1, Amadori albumin, and complications of type 1 diabetes: the EURODIAB prospective complications study

Objective-Transforming growth factor (TGF)-beta1 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-beta1 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-beta1 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-beta1) and 1.67 (1.34-2.07, P=0.001 for Amadori albumin). The SIZE for urinary TGF-beta1 remained statistically significant when adjusted for HbA(1c) Amadori albumin, and blood pressure. Circulating TGF-beta1 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-beta1 in macroalbuminuria were associated with elevations in Amadori albumin and HbA(1c) and also in blood pressure. In contrast, only circulating TGF-beta1 was related to proliferative retinopathy, and HbA(1c) largely accounted for this. These findings may indicate novel pathways for understanding mechanisms and therapeutic interventions