Vantyghem M C, Balduyck M, Zerimech F, Martin A, Douillard C, Bans S, Degand P M, Lefebvre J
Endocrinology Department, Biochemistry Laboratory, CHRU, Lille, France.
J Endocrinol Invest. 2000 Dec;23(11):732-6. doi: 10.1007/BF03345062.
Oxidative stress has been implicated in the pathogenesis of the chronic complications of diabetes mellitus but little is known in diabetic ketoacidosis (DKA). The aim of this work was to determine whether lipid peroxidation, as assessed by measuring malondialdehyde (MDA, a prooxidant) and antioxidant status (TAS, an index of antioxidant defenses), is modified in DKA, and also whether any observed abnormalities were related to metabolic disturbances.
four groups of patients were studied, comprising 19 patients with DKA, massive ketonuria and plasma standard bicarbonate levels below 16 mmol/l (group 1); 20 patients with poorly controlled diabetes, glycated hemoglobin (HbA1c) above 8% and plasma bicarbonate levels above 16 mmol/l (group 2); 11 patients with well-controlled diabetes and HbA1c below 8% (group 3); and 10 non-diabetic, non-obese control subjects (group 4). Metabolic parameters, MDA levels and TAS were assessed in the plasma of the four groups of subjects.
mean plasma MDA and TAS values were significantly different among the four groups (respectively p < 0.001 and p < 0.01). Mean plasma MDA value was significantly higher in group 1 than in group 3 (p < 0.02) and group 4 (p < 0.001) but was not different from that in group 2. Mean plasma MDA value in group 2 was significantly lower than that in group 4 (p = 0.002). Mean plasma TAS value in group 1 was significantly lower than in groups 3 (p < 0.002) and 4 (p < 0.05). Mean plasma TAS value was significantly lower in group 2 than in group 4 (p<0.05). Plasma MDA values in the diabetic patients (groups 1+2+3) were not related to any clinical characteristics (BMI, age, duration of the disease) or metabolic parameters (glycemia, HbA1c bicarbonates, blood urea nitrogen, phosphatemia, lipids), while plasma TAS values correlated negatively with glycemia, osmolality and HbA1c. A significant relationship was also found between TAS and HbA1c in group 1 (p < 0.05) and between MDA and HbA1c in group 3 (p < 0.05). Correlations were also found between TAS and phosphatemia in group 1 (p < 0.01) and between MDA and phosphatemia in group 2 (p < 0.01). A positive relationship between MDA and cholesterol levels was found in group 1 (p < 0.01). In conclusion, MDA values are increased and TAS values decreased in DKA and poorly controlled diabetes, and tend to correlate more with markers of diabetic imbalance than with markers of acute metabolic disturbances of DKA.
氧化应激与糖尿病慢性并发症的发病机制有关,但在糖尿病酮症酸中毒(DKA)方面了解甚少。本研究的目的是确定通过测量丙二醛(MDA,一种促氧化剂)评估的脂质过氧化和抗氧化状态(TAS,抗氧化防御指标)在DKA中是否发生改变,以及任何观察到的异常是否与代谢紊乱有关。
研究了四组患者,包括19例患有DKA、大量酮尿且血浆标准碳酸氢盐水平低于16 mmol/L的患者(第1组);20例糖尿病控制不佳、糖化血红蛋白(HbA1c)高于8%且血浆碳酸氢盐水平高于16 mmol/L的患者(第2组);11例糖尿病控制良好且HbA1c低于8%的患者(第3组);以及10名非糖尿病、非肥胖对照受试者(第4组)。评估了四组受试者血浆中的代谢参数、MDA水平和TAS。
四组之间的平均血浆MDA和TAS值有显著差异(分别为p < 0.001和p < 0.01)。第1组的平均血浆MDA值显著高于第3组(p < 0.02)和第4组(p < 0.001),但与第2组无差异。第2组的平均血浆MDA值显著低于第4组(p = 0.002)。第1组的平均血浆TAS值显著低于第3组(p < 0.002)和第4组(p < 0.05)。第2组的平均血浆TAS值显著低于第4组(p<0.05)。糖尿病患者(第1 + 2 + 3组)的血浆MDA值与任何临床特征(BMI、年龄、病程)或代谢参数(血糖、HbA1c、碳酸氢盐、血尿素氮、磷血症、血脂)均无关联,而血浆TAS值与血糖、渗透压和HbA1c呈负相关。在第1组中还发现TAS与HbA1c之间存在显著关系(p < 0.05),在第3组中MDA与HbA1c之间存在显著关系(p < 0.05)。在第1组中还发现TAS与磷血症之间存在相关性(p < 0.01),在第2组中MDA与磷血症之间存在相关性(p < 0.01)。在第1组中发现MDA与胆固醇水平之间存在正相关(p < 0.01)。总之,DKA和糖尿病控制不佳时MDA值升高而TAS值降低,并且与糖尿病失衡标志物的相关性往往比与DKA急性代谢紊乱标志物的相关性更强。