title: Serum extracellular superoxide dismutase in patients with type 2 diabetes: relationship to the development of micro- and macrovascular complications.
abstract: 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.
  
  
  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.
authors.affiliation: First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kimura
authors.forename: Goji
authors.initials: G
authors.lastname: Hasegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Michiaki
authors.initials: M
authors.lastname: Fukui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Hyohun
authors.initials: H
authors.lastname: Park
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Nakano
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D019943:Amino Acid Substitution; D001120:Arginine; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000453:epidemiology*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D005998:Glycine; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D020125:Mutation, Missense; D010641:Phenotype; D011237:Predictive Value of Tests; D012044:Regression Analysis; D013482:Superoxide Dismutase / Q000097:blood* / Q000235:genetics*
chemical_list: D001120:Arginine; D002784:Cholesterol; D003404:Creatinine; D006442:Glycated Hemoglobin; D005998:Glycine; D013482:Superoxide Dismutase