The natural history of diabetic neuropathy and its risk factors are not well understood. The potential association of various lipids [e.g., high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides], and lipoprotein(a) [Lp(a)] concentrations, with large sensory nerve fiber function as assessed by vibratory thresholds was examined in a group of 91 individuals with diabetes mellitus. In multivariate analyses, no independent relationships of any of the lipid or lipoprotein parameters measured in this study were found with vibratory thresholds (i.e., dependent variable). Independent associations of age, duration of diabetes, height, and medications that lower blood pressure with vibratory thresholds were shown and explained 51% of the overall variability of the model. In gender-specific models, age, height, and medications that lower blood pressure were statistically significant independent determinates (i.e., males R2 = 0.61, females R2 = 0.39). These cross-sectional data suggest that lipid and lipoprotein parameters measured in this study have little association with large sensory nerve fiber dysfunction. The interesting association with the use of medications that lower blood pressure and vibratory thresholds warrants further investigation.