Oxidative markers in diabetic ketoacidosis

Abstract

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.

Methods: 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.

Results: 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.