title: Short-term insulin therapy and normoglycemia. Effects on erythrocyte lipid peroxidation in NIDDM patients.
abstract: OBJECTIVE
  To evaluate erythrocyte lipid peroxidation (LPO) before and after an adaptive short-term insulin therapy in NIDDM patients who were chronically hyperglycemic.
  
  
  METHODS
  Twenty-six patients with NIDDM (mean HbA1c, 11.28%) aged 53.04 +/- 2.03 years were submitted for 3 days to constant intravenous glucose and continuous insulin perfusion at an adaptable rate to maintain glycemia within the normal range. An evaluation of LPO at baseline and after euglycemic insulin therapy was determined by erythrocyte free and total malondialdehyde (MDA) levels, polyunsaturated fatty acid (PUFA) percentage, vitamin E and glutathione content, and the following antioxidant enzymatic activity determinations: glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). Fasting serum glucose, HbA1c, triglycerides, cholesterol, and HDL cholesterol levels were also determined at these time points.
  
  
  RESULTS
  At baseline, erythrocyte free and total MDA were significantly higher in NIDDM patients than in control subjects (11.14 +/- 0.80 vs. 1.74 +/- 0.11 nmol/g Hb [P < 0.0001] for free MDA; 18.04 +/- 1.79 vs. 7.85 +/- 0.55 nmol/g Hb [P < 0.0001] for total MDA). PUFAs, particularly C20:4 and C22:5, were increased (14.69 +/- 0.34 vs. 12.03 +/- 0.31 and 2.31 +/- 0.04 vs. 1.71 +/- 0.03% of total fatty acids, respectively). Vitamin E and glutathione were reduced significantly (6.16 +/- 0.61 vs. 14.84 +/- 0.64 nmol/g Hb and 0.42 +/- 0.04 vs. 0.97 +/- 0.06 mmol/l, respectively). No difference was observed for the enzymatic activities. After euglycemic insulin therapy, triglycerides significantly decreased compared with baseline concentrations (1.55 +/- 0.13 vs. 2.42 +/- 0.22 mmol/l; P < 0.001), whereas other lipidic parameters were unchanged. Free MDA significantly decreased (8.60 +/- 0.76 vs. 11.14 +/- 0.80 nmol/g Hb [P < 0.01]), while vitamin E increased (7.93 +/- 0.73 vs. 6.16 +/- 0.61 nmol/g Hb [P < 0.05]). No difference was observed for PUFAs, glutathione, or total MDA.
  
  
  CONCLUSIONS
  The observed erythrocyte LPO in NIDDM decreased after a short-term adaptive insulin therapy. This decrease could be principally attributed to the normalized glycemia that reduces reactive oxygen species (ROS) production, which in turn may explain the increase in erythrocyte membrane vitamin E and the decrease in MDA. This study shows the value of a euglycemic environment in NIDDM to reduce LPO and, at long range, to minimize clinical diabetes complications.
authors.affiliation: Laboratoire Biochimie Médicale, Université Bordeaux, France.
authors.forename: E
authors.initials: E
authors.lastname: Peuchant
authors.forename: M C
authors.initials: MC
authors.lastname: Delmas-Beauvieux
authors.forename: A
authors.initials: A
authors.lastname: Couchouron
authors.forename: L
authors.initials: L
authors.lastname: Dubourg
authors.forename: M J
authors.initials: MJ
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Perromat
authors.forename: M
authors.initials: M
authors.lastname: Clerc
authors.forename: H
authors.initials: H
authors.lastname: Gin
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D004912:Erythrocytes / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D005227:Fatty Acids / Q000097:blood / Q000145:classification; D005260:Female; D015309:Glucose Clamp Technique; D005978:Glutathione / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D014810:Vitamin E / Q000097:blood
chemical_list: D000975:Antioxidants; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D014810:Vitamin E; D008315:Malondialdehyde; D005978:Glutathione