Electronegative low density lipoprotein subform (LDL-) is increased in type 2 (non-insulin-dependent) microalbuminuric diabetic patients and is closely associated with LDL susceptibility to oxidation.

There is increasing evidence that diabetes mellitus is characterized by an enhanced lipoprotein oxidation. We have therefore investigated whether a relationship exists between LDL oxidation and microalbuminuria, which is considered an early marker of vascular involvement in type 2 diabetic patients. We selected 12 microalbuminuric and 12 normoalbuminuric type 2 diabetic patients, and 12 control subjects comparable for age, sex and blood pressure values. Oxidatively modified plasma LDL, referred as LDL-, were measured by ion-exchange HPLC. In vitro susceptibility to oxidation of LDL was evaluated by following the kinetics of conjugated diene formation in the presence of Cu++ ions (lag-phase time). Microalbuminuric diabetic patients had a less satisfactory metabolic control and showed a higher plasma triglyceride concentration than both normoalbuminuric diabetic patients (2.211+/-1.01 vs 1.15+/-0.39 mmol/l, P<0.O1) and controls (1.18+/-0.61 mmol/l, P<0.01 ). The percentage of LDL- in plasma was significantly increased in microalbuminuric diabetic patients in comparison with both normoalbuminuric diabetic patients (5.24+/-1.67 vs 3.13+/-1.22%, P<0.01) and controls (2.34+/-1.03%, P<0.001). LDL isolated from microalbuminuric diabetic patients had a significantly shorter lag-phase time in comparison with normoalbuminuric diabetic patients (79+/-11 vs 97+/-10 min, P<0.05) and controls (120+/-24 min. P<0.001). In diabetic patients a significant linear correlation was observed between the percentage of LDL and amount of fructosamine (r=0.45, P<0.05), HbA1c (r=0.41, P<0.05), and triglycerides (r=0.65, P<0.001). An inverse correlation was found between lag-phase time and fructosamine (r=-0.5, P<0.01) and triglycerides (r=-0.59, P<0.001). This study shows that microalbuminuric type 2 diabetic patients had evidence of increased LDL oxidation, which seems to be mainly due to a poor metabolic control and a more atherogenic lipid profile.