Diabetes Care, Vol 20, Issue 2 202-207, Copyright © 1997 by American Diabetes Association
Short-term insulin therapy and normoglycemia. Effects on erythrocyte lipid peroxidation in NIDDM patients
E Peuchant, MC Delmas-Beauvieux, A Couchouron, L Dubourg, MJ Thomas, A Perromat, M Clerc and H Gin
Laboratoire Biochimie Medicale, Universite Bordeaux, France.
OBJECTIVE: To evaluate erythrocyte lipid peroxidation (LPO) before and
after an adaptive short-term insulin therapy in NIDDM patients who were
chronically hyperglycemic. RESEARCH DESIGN AND 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.