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 b y an enhanced lipoprotein oxidation. We have therefore investigated wh ether 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 normoalbum inuric type 2 diabetic patients, and 12 control subjects comparable fo r age, sex and blood pressure sure values. Oxidatively modified plasma LDL, referred as LDL-, were measured by ion-exchange HPLC. In vitro s usceptibility to oxidation of LDL was evaluated by following the kinet ics of conjugated diene formation in the presence of Cu++ ions (lag-ph ase time). Microalbuminuric diabetic patients had a less satisfactory metabolic control and showed a higher plasma triglyceride concentratio n than both normoalbuminuric diabetic patients (2.21 +/- 1.01 vs 1.15 +/- 0.39 mmol/l, P < 0.01) and controls (1.18 +/- 0.61 mmol/l, P < 0.0 1). The percentage of LDL- in plasma was significantly increased in mi croalbuminuric diabetic patients in comparison with both normoalbuminu ric 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 microalbuminur ic diabetic patients had a significantly shorter lag-phase time in com parison with normoalbuminuric diabetic patients (79 +/- 11 vs 97 +/- 1 0 min, P < 0.05) and controls (120 +/- 24 min, P < 0.001). In diabetic patients a significant linear correlation was observed between the pe rcentage of LDL- and amount of fructosamine (r = 0.45, P < 0.05), HbA( 1c) (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 st udy shows that microalbuminuric type 2 diabetic patients had evidence of increased LDL oxidation, which seems to be mainly due to a poor met abolic control and a more atherogenic lipid profile.