Connective Tissue Growth Factor Is Increased in Plasma of Type 1 Diabetic Patients With Nephropathy

  1. Peggy Roestenberg, MSC1,
  2. Frans A. van Nieuwenhoven, PHD1,
  3. Lotte Wieten, MSC1,
  4. Peter Boer, PHD2,
  5. Theo Diekman, MD, PHD3,
  6. Anna M. Tiller, MD4,
  7. Wilmar M. Wiersinga, MD, PHD3,
  8. Noelynn Oliver, PHD5,
  9. William Usinger, PHD5,
  10. Stephen Weitz, PHD5,
  11. Reinier O. Schlingemann, MD, PHD4 and
  12. Roel Goldschmeding, MD, PHD1
  1. 1Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands
  3. 3Department of Endocrinology & Metabolism, Academic Medical Center, Amsterdam, the Netherlands
  4. 4Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands
  5. 5FibroGen, South San Francisco, California
  1. Address correspondence and reprint requests to Dr. Roel Goldschmeding, University Medical Center, Department of Pathology, H04.312, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands. E-mail: r.goldschmeding{at}azu.nl

Abstract

OBJECTIVE—Connective tissue growth factor (CTGF) is strongly upregulated in fibrotic disorders and has been hypothesized to play a role in the development and progression of diabetes complications. The aim of the present study was to investigate the possible association of plasma CTGF levels in type 1 diabetic patients with markers relevant to development of diabetes complications.

RESEARCH DESIGN AND METHODS—Plasma CTGF levels (full-length and NH2-terminal fragments) were determined in 62 well-characterized patients with type 1 diabetes and in 21 healthy control subjects. Correlations of these plasma CTGF levels with markers of glycemic control, platelet activation, endothelial activation, nephropathy, and retinopathy were investigated.

RESULTS—Elevated plasma NH2-terminal fragment of CTGF (CTGF-N) levels were detected in a subpopulation of type 1 diabetic patients and were associated with diabetic nephropathy. Stepwise regression analysis revealed contribution of albuminuria, creatinine clearance, and duration of diabetes as predictors of plasma CTGF-N level. Elevation of plasma CTGF-N levels in patients with retinopathy was probably due to renal comorbidity.

CONCLUSIONS—Plasma CTGF-N levels are elevated in type 1 diabetic patients with nephropathy and appear to be correlated with proteinuria and creatinine clearance. Further studies will be needed to determine the relevance of plasma CTGF as a clinical marker and/or pathogenic factor in diabetic nephropathy.

Footnotes

  • R.O.S. has received research funds from FibroGen. R.G. has received research funds and fees for speaking engagements from FibroGen.

    • Accepted January 29, 2004.
    • Received September 4, 2003.
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  1. doi: 10.2337/diacare.27.5.1164 Diabetes Care May 2004 vol. 27 no. 5 1164-1170
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