Insulin sensitivity in type 2 diabetes is closely associated with LDL particle size

PRINCIPLES: Small dense LDLs have been found to be associated with type 2 diabetes (T2DM). This association has been observed in the context of decreased HDL cholesterol and increased triglycerides. METHODS: In the present study the relationship between LDL particle size and insulin sensitivity was assessed in 46 patients with T2DM (mean age 60 (11) years, HbA1c 7.6 (0.8) %). 75 g oral glucose tolerance testing was performed and composite insulin sensitivity index was calculated by the method of Matsuda and de Fronzo (ISI(comp)). Additional parameters included BMI, waist circumference, blood pressure, HDL cholesterol, triglycerides and LDL cholesterol. LDL particle size was measured by gradient gel electrophoresis. RESULTS: Log ISI(comp) correlated most strongly with LDL particle size (R = 0.61), less closely with HDL cholesterol (R = 0.48) and plasma triglycerides (R = -0.45) and not at all with LDL cholesterol (R = 0.001), as supported by multiple regression analyses where log ISI(com) was associated with LDL particle size (p = 0.004) and HDL cholesterol (p = 0.027) but not with triglycerides and LDL cholesterol. CONCLUSION: Log ISI(comp) estimated by a formula using endogenous insulin levels is very closely associated with LDL particle size in patients with T2DM. Our data suggest that smaller LDL particle size reflects the impact of insulin resistance on lipoprotein metabolism more strictly than do the traditional lipid parameters.