Serum Extracellular Superoxide Dismutase in Patients With Type 2 Diabetes

Relationship to the development of micro- and macrovascular complications

  1. Fumiaki Kimura, MD1,
  2. Goji Hasegawa, MD1,
  3. Hiroshi Obayashi, PHD12,
  4. Tetsuo Adachi, PHD3,
  5. Hirokazu Hara, PHD3,
  6. Mitsuhiro Ohta, PHD4,
  7. Michiaki Fukui, MD1,
  8. Yoshihiro Kitagawa, MD1,
  9. Hyohun Park, MD1,
  10. Naoto Nakamura, MD1,
  11. Koji Nakano, MD5 and
  12. Toshikazu Yoshikawa, MD1
  1. 1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
  2. 2Kyoto Microbiological Institute, Kyoto, Japan
  3. 3Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
  4. 4Department of Clinical Chemistry, Kobe Pharmaceutical University, Kobe, Japan
  5. 5Department of Internal Medicine, Yamashiro Hospital, Kyoto, Japan


    OBJECTIVE—The aim of this study was to determine the distribution of serum extracellular superoxide dismutase (EC-SOD) concentrations in patients with type 2 diabetes and to assess whether increased EC-SOD concentration is associated with the development of diabetic vascular complications.

    RESEARCH DESIGN AND METHODs—Serum EC-SOD concentrations were determined in 222 patients with type 2 diabetes and 75 healthy control subjects by an enzyme-linked immunosorbent assay. All subjects had the EC-SOD domain genotyped.

    RESULTS—The serum EC-SOD concentrations showed a distinct bimodal distribution in both patients with diabetes and control subjects. All subjects with the high-level phenotype carried the Arg213Gly mutation. The frequency of this variant was similar in the diabetes and control groups. Within the group of subjects with the common EC-SOD phenotype, the serum EC-SOD concentration (mean ± SE) was significantly higher in patients with type 2 diabetes (99.3 ± 1.3 ng/ml) compared with the control subjects (68.4 ± 2.3 ng/ml, P < 0.01). Stepwise multiple regression analysis of the data from the diabetic common phenotype group showed a significant relationship between serum EC-SOD concentration and duration of diabetes (F = 5.31), carotid artery intimal-media thickness (F = 8.24), and severity of nephropathy (F = 16.05) and retinopathy (F = 4.43).

    CONCLUSIONS—We observed a strong relationship between the serum concentration of EC-SOD and the severity of both micro- and macrovascular diabetic complications. These findings suggest that serum EC-SOD concentration levels may be a marker of vascular injury, possibly reflecting hyperglycemia-induced oxidative injury to the vascular endothelium and decreased binding of EC-SOD to the vascular wall.


    • Address correspondence and reprint requests to Dr. Goji Hasegawa, the First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamikyo-ku, Kyoto 602-0841, Japan. E-mail: goji{at}

      Received for publication 23 July 2002 and accepted in revised form 30 December 2002.

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

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