ENHANCED SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO IN-VITRO OXIDATION IN TYPE-1 AND TYPE-2 DIABETIC-PATIENTS

Macrovascular disease represents a major cause of morbidity and mortal ity in patients with diabetes mellitus. Low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions, through mo difying processes such as oxidation. We examined the in vitro suscepti bility to oxidation and the oxidizability of LDL isolated from the pla sma of Type 1 and Type 2 diabetic patients. Two groups of diabetic pat ients (20 Type 1, 20 Type 2) were compared with sex- and age-matched n on-diabetic control groups. In vitro oxidation of the purified LDL pre parations was assessed by determination of the kinetics for the format ion of conjugated dienes (lag phase duration, maximal rate and maximal dienes concentration) and by measurement of thiobarbituric acid-react ing substances (TEARS) in the presence of copper ions. LDL from both T ype 1 and Type 2 diabetic patients exhibited a shorter lag phase durat ion for conjugated dienes formation (94 +/- 14 vs. 108 +/- 20 and 97 /- 26 vs. 112 +/- 18 min for Type 1 and Type 2 diabetic groups vs, res pective control groups, P < 0.05). We also observed an increase in max imal rate of conjugated dienes formation (2.21 +/- 0.55 vs. 1.52 +/- 0 .31 and 2.02 +/- 0.55 vs, 1.52 +/- 0.31 nmol/mg LDL/min, P < 0.01) and of maximal production of TEARS (77.9 +/- 11.8 vs, 65.5 +/- 10.4 and 7 6.7 +/- 9.9 vs. 65.3 +/- 9.4 nmol/mg LDL protein, P < 0.05) in diabeti c groups. Our results demonstrate both a higher susceptibility to oxid ation and a higher oxidizability of LDL from diabetic patients, as muc h for Type 1 as Type 2 diabetic subjects with or without pre-existent vascular complications. This enhanced propensity of LDL oxidation in p atients with diabetes mellitus could at least partly be attributable t o quantitative and qualitative alterations in the chemical composition of LDL and to the glycoxidation process occurring on these lipoprotei ns.