Connective tissue growth factor and susceptibility to renal and vascular disease risk in type 1 diabetes

Abstract

Objective: We explored the relevance and significance of connective tissue growth factor (CTGF) as a determinant of renal and vascular complications among type 1 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 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (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. The relative risk for increased carotid intima-media thickness was higher in patients with concomitantly elevated plasma CTGF N fragment and macroalbuminuria relative to patients with normal plasma CTGF N fragment and normal albuminuria (relative risk = 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.

Figure 1

Log CTGF N fragment vs. cumulative distribution of hypertension status in the DCCT/EDIC cohort. The plasma CTGF N fragment levels in patients with hypertension are significantly higher than patients with normal blood pressure (P = 0.0005; n = 1050).