Effect of intensive lipid-lowering strategy on low-density lipoprotein particle size in patients with type 2 diabetes mellitus

A preponderance of small dense LDL particles is strongly associated with the occurrence of atherosclerotic disease. Although several studies have documented an increased prevalence of small dense LDL particles in diabetes mellitus no data are available to show the effect of lipid-lowering treatment upon the improvement of LDL particle size. In the present study we examined the effect of lipid-lowering treatment, following an intensive lipid-lowering strategy for 30 weeks pursuing ADA recommended target lipid levels, on LDL particle size in 50 type 2 diabetic patients with moderate hyperlipidemia. At week 0, 24 patients (48%) were characterized by small dense LDL phenotype pattern B. After the treatment period a shift towards normal LDL particle size was observed in 17 patients but seven patients (29%) showed the more atherogenic LDL subclass pattern B. After treatment, plasma HDL-cholesterol was significantly lower (P<0.05) in these patients compared to those who had LDL subclass pattern A. Multivariate regression analysis revealed VLDL-cholesterol or triglycerides and HDL3-cholesterol as independent determinants for LDL particle size. Change in HDL2-cholesterol was an independent determinant for change in LDL particle size. In conclusion, a strategy of intensive lipid-lowering, with the intention to reduce triglyceride levels below 1.7 mmol/l, may be insufficient to ensure improvement in LDL size in all patients.