Relationship of LDL size to insulin sensitivity in normoglycemic men

A preponderance of small, dense LDL has been suggested to be more atherogenic than larger, more buoyant LDL. Although several studies have suggested associations of small, dense LDL with hyperinsulinemia, few data are available on the relation of small, dense LDL to insulin resistance. We examined the association of LDL particle size determined by gradient gel electrophoresis with the rates of whole-body glucose uptake (WBGU) as determined by the hyperinsulinemic euglycemic clamp with indirect calorimetry in 87 Finnish normoglycemic men. LDL size was significantly positively correlated with the rates of WBGU (overall, r = .31, P < .01; oxidative, r = .23, P < .05; and nonoxidative, r = .31, P < .01). Rates of WBGU were also significantly lower in subjects with small LDL particles (< or = 26.0 nm) compared with those in subjects with larger LDL particles (> 26.0 nm). This relation was not explained by obesity. Serum triglyceride concentrations were found to significantly affect the relationship of LDL particle size to WBGU. Specifically, LDL size was correlated with the rates of WBGU in men with mildly elevated triglyceride levels but not in men with low triglyceride levels. Serum VLDL triglyceride concentration was a substantially stronger determinant of LDL size than were the rates of WBGU. WBGU was not significantly related to LDL size when adjusted for triglycerides. We conclude that a preponderance of small, dense LDL particles is associated with insulin resistance and that serum triglyceride concentration modifies this relationship.