Effect of insulin treatment on plasma oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients

Objective: In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. Research design and Methods: Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. Results: Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P < 0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1 +/- 4.7 vs. 24.0 +/- 5.8 U/mmol, P < 0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. Conclusions: In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.