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


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).


CONCLUSIONS
These findings demonstrate that plasma CTGF is a risk marker of diabetic renal and vascular disease.
Jaffa
Ayad A
AA
Department of Medicine, Endocrinology-Diabetes-Medical Genetics, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29425, USA. jaffaa@musc.edu
Usinger
William R
WR
McHenry
M Brent
MB
Jaffa
Miran A
MA
Lipstiz
Stuart R
SR
Lackland
Daniel
D
Lopes-Virella
Maria
M
Luttrell
Louis M
LM
Wilson
Peter W F
PW
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000209:etiology; D001794:Blood Pressure; D002339:Carotid Arteries / Q000473:pathology; D015331:Cohort Studies; D055513:Connective Tissue Growth Factor; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000209:etiology*; D003928:Diabetic Nephropathies / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood* / Q000652:urine; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000652:urine; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000652:urine
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D055513:Connective Tissue Growth Factor