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Connective Tissue Growth Factor and Susceptibility to Renal and Vascular Disease Risk in Type 1 Diabetes

Department of Medicine (A.A.J., M.L.-V., L.M.L., P.W.F.W.), Division of Endocrinology-Diabetes-Medical Genetics, Medical and Department of Bioinformatics, Biostatistics, and Epidemiology (M.B.M., M.A.J., S.R.L., D.L.), Medical University of South Carolina, Charleston, South Carolina; and FibroGen Inc. (A.A.J., W.R.U.), South San Francisco, California

Address all correspondence and requests for reprints to: Ayad A. Jaffa, Ph.D., Department of Medicine, Endocrinology-Diabetes-Medical Genetics, Medical University of South Carolina, 114 Doughty Street, P.O. Box 250776, Charleston, South Carolina 29425. E-mail: jaffaa{at}musc.edu.

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.