Decreased Endogenous Secretory Advanced Glycation End Product Receptor in Type 1 Diabetic Patients

Its possible association with diabetic vascular complications

  1. Naoto Katakami, MD, PHD1,
  2. Munehide Matsuhisa, MD, PHD1,
  3. Hideaki Kaneto, MD, PHD1,
  4. Taka-aki Matsuoka, MD, PHD1,
  5. Ken’ya Sakamoto, MD, PHD1,
  6. Yoshihisa Nakatani, MD, PHD1,
  7. Kentaro Ohtoshi, MD, PHD2,
  8. Rieko Hayaishi-Okano, MD, PHD1,
  9. Keisuke Kosugi, MD, PHD2,
  10. Masatsugu Hori, MD, PHD1 and
  11. Yoshimitsu Yamasaki, MD, PHD1
  1. 1Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, Osaka, Japan
  2. 2Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan
  1. Address correspondence and reprint requests to Naoto Katakami, MD, PhD, Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: katakami{at}medone.med.osaka-u.ac.jp

Abstract

OBJECTIVE—The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications.

RESEARCH DESIGN AND METHODS—Circulating esRAGE levels in serum were examined in 67 Japanese type 1 diabetic patients (22 men and 45 women, age 24.0 ± 4.4 years [means ± SD]) and 23 age-matched healthy nondiabetic subjects (10 men and 13 women aged 24.9 ± 1.4 years). Daily urinary albumin excretion, the presence of retinopathy, and intima-media thickness (IMT) of the carotid artery were also evaluated. We further explored the association between esRAGE levels and severity of diabetic vascular complications.

RESULTS—Circulating esRAGE levels were significantly lower in subjects with type 1 diabetes than in nondiabetic subjects (0.266 ± 0.089 vs. 0.436 ± 0.121 ng/ml, respectively, P < 0.0001) and was inversely correlated with HbA1c (A1C) levels (r = −0.614, P < 0.0001). In addition, multivariate regression analysis demonstrated that A1C was an independent risk factor for a low esRAGE value. Furthermore, circulating esRAGE levels were inversely correlated with carotid IMT (r = −0.325, P = 0.0017) and was one of the independent risk factors for IMT thickening. Furthermore, there was a significant difference (P = 0.0124) in esRAGE levels between patients without retinopathy (0.286 ± 0.092 ng/ml) and those with retinopathy (0.230 ± 0.074 ng/ml).

CONCLUSIONS—Circulating esRAGE levels were significantly lower in type 1 diabetic patients than in nondiabetic subjects and were inversely associated with the severity of some diabetic vascular complications.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted July 28, 2005.
    • Received May 17, 2005.
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