Serum Extracellular Superoxide Dismutase in Patients With Type 2 Diabetes
Relationship to the development of micro- and macrovascular complications
- Fumiaki Kimura, MD1,
- Goji Hasegawa, MD1,
- Hiroshi Obayashi, PHD12,
- Tetsuo Adachi, PHD3,
- Hirokazu Hara, PHD3,
- Mitsuhiro Ohta, PHD4,
- Michiaki Fukui, MD1,
- Yoshihiro Kitagawa, MD1,
- Hyohun Park, MD1,
- Naoto Nakamura, MD1,
- Koji Nakano, MD5 and
- Toshikazu Yoshikawa, MD1
- 1First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
- 2Kyoto Microbiological Institute, Kyoto, Japan
- 3Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan
- 4Department of Clinical Chemistry, Kobe Pharmaceutical University, Kobe, Japan
- 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.
- EC-SOD, extracellular superoxide dismutase
- IMT, intimal-media thickness
- NDR, no diabetic retinopathy
- PDR, proliferative diabetic retinopathy
- PPDR, preproliferative diabetic retinopathy
- SDR, simple diabetic retinopathy
- UACR, urinary albumin-to-creatinine ratio
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:.
Received for publication 23 July 2002 and accepted in revised form 30 December 2002.
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