Objective: We explored the relevance and significance of connective tissue growth factor (CTGF) as determinants of renal and vascular complications among type I diabetic patients.

Methods and Results: We measured the circulating and urinary levels of CTGF and CTGF N fragment in 1050 subjects with type 1 diabetes from the DCCT/EDIC Study cohort. We found that hypertensive diabetic subjects have significantly higher levels of plasma log CTGF N fragment relative to normotensive subjects (P=0.0005). Multiple regression analysis showed a positive and independent association between CTGF N fragment levels and log albumin excretion rate (P<0.0001). In categorical analysis, patients with macroalbuminuria had higher levels of CTGF N fragment than diabetic subjects with or without microalbuminuria (P<0.0001). Univariate and multiple regression analyses demonstrated an independent and significant association of log CTGF N fragment with the common and internal carotid intima-media thickness (IMT). The relative risk (RR) for increased carotid IMT was higher in patients with concomitantly plasma CTGF N fragment elevations and macroalbuminuria relative to patients with normal plasma CTGF N fragment and normal albuminuria (RR=4.76; 95% confidence interval, 2.21–10.25, P<0.0001).

Conclusion: These findings demonstrate that plasma CTGF is a risk marker of diabetic renal and vascular disease.