Peuchant E, Delmas-Beauvieux M C, Couchouron A, Dubourg L, Thomas M J, Perromat A, Clerc M, Gin H
Laboratoire Biochimie Médicale, Université Bordeaux, France.
Diabetes Care. 1997 Feb;20(2):202-7. doi: 10.2337/diacare.20.2.202.
To evaluate erythrocyte lipid peroxidation (LPO) before and after an adaptive short-term insulin therapy in NIDDM patients who were chronically hyperglycemic.
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.
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.
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.
评估长期血糖升高的非胰岛素依赖型糖尿病（NIDDM）患者在短期适应性胰岛素治疗前后的红细胞脂质过氧化（LPO）情况。
26例年龄为53.04±2.03岁的NIDDM患者（平均糖化血红蛋白[HbA1c]为11.28%），接受为期3天的持续静脉输注葡萄糖和以可调节速率持续输注胰岛素，以维持血糖在正常范围内。通过红细胞游离和总丙二醛（MDA）水平、多不饱和脂肪酸（PUFA）百分比、维生素E和谷胱甘肽含量，以及以下抗氧化酶活性测定来评估基线和血糖正常的胰岛素治疗后的LPO：谷胱甘肽过氧化物酶（GPX）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）。在这些时间点还测定了空腹血糖、HbA1c、甘油三酯、胆固醇和高密度脂蛋白胆固醇水平。
基线时，NIDDM患者的红细胞游离和总MDA显著高于对照组（游离MDA：11.14±0.80 vs. 1.74±0.11 nmol/g Hb [P<0.0001]；总MDA：18.04±1.79 vs. 7.85±0.55 nmol/g Hb [P<0.0001]）。PUFA，尤其是C20:4和C22:5增加（分别占总脂肪酸的14.69±0.34% vs. 12.03±0.31%和2.31±0.04% vs. 1.71±0.03%）。维生素E和谷胱甘肽显著降低（分别为6.16±0.61 vs. 14.84±0.64 nmol/g Hb和0.42±0.04 vs. 0.97±0.06 mmol/l）。酶活性未观察到差异。血糖正常的胰岛素治疗后，甘油三酯与基线浓度相比显著降低（1.55±0.13 vs. 2.42±0.22 mmol/l；P<0.001），而其他脂质参数未改变。游离MDA显著降低（8.60±0.76 vs. 11.14±0.80 nmol/g Hb [P<0.01]），而维生素E增加（7.93±0.73 vs. 6.16±0.61 nmol/g Hb [P<0.05]）。PUFA、谷胱甘肽或总MDA未观察到差异。
短期适应性胰岛素治疗后，NIDDM患者中观察到的红细胞LPO降低。这种降低可能主要归因于血糖正常化，血糖正常化减少了活性氧（ROS）的产生，这反过来可能解释了红细胞膜维生素E的增加和MDA的降低。本研究显示了血糖正常环境在NIDDM中降低LPO以及长期减少临床糖尿病并发症的价值。
