Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus

Background: Patients with diabetes mellitus have been reported to show increased serum levels of modified low-density lipoprotein (LDL), including glycosylated, oxidized and small, dense LDL. This change has been suggested to represent an important risk factor for diabetic macroangiopathy. A common characteristic shared by these modified LDL species is the increase in electronegative charge on particle surfaces, which can be detected by agarose gel electrophoresis as “LDL charge modified frequency” (LDL-CMF) determined from the relative mobility of LDL fraction. Methods: LDL-CMF was measured in the sera from 129 outpatients with type 2 diabetes mellitus and compared with the data from 34 normal subjects. Results: The LDL fraction from diabetics migrates more closely to the anode side as compared with that from normal subjects. The LDL-CMF measured in diabetics, 5.5±8.1%, was significantly (p<0.0001) higher than 0.6±3.4% in normal subjects. Serum LDL-CMF showed significant positive correlations with triglyceride at r=0.552 (p<0.0001) and malondialdehyde modified LDL at r=0.390 (p<0.0001), as well as systolic blood pressure, body mass index, fasting plasma glucose, hemoglobin A_1c, total cholesterol, free fatty acid (FFA) and homeostasis model assessment ratio. It showed negative correlations with high-density lipoprotein and total superoxide dismutase activity. Conclusion: The results indicate that LDL-CMF reflects the degree of serum LDL modification in diabetics and can be regarded as an important risk factor for diabetic macroangiopathy.