Lipoprotein composition was determined using ultracentrifugation in 20 non&#151;insulin-dependent (NIDDM) diabetic patients on diet only (D), 20 NIDDM patients on diet and sulfonylorea therapy (T), and 20 nondiabetic control subjects (C), all of whom had total plasma cholesterol concentrations <6.5 mmol/L and total plasma triglyceride concentrations <3.0 mmol/L. Although the groups were well matched for age, body mass index, total triglyceride levels, and total cholesterol concentrations, there were significant compositional abnormalities in the low-density lipoprotein (LDL) fractions of diabetic subjects. The LDL total lipid to apolipoprotein B weight ratio (representing the density distributions of LDL particles) was reduced in both diabetic groups: 3.75±0.3, 3.50±0.28, and 3.54±0.22 in C, D, and T groups, respectively (mean±SD;p<.05). This was associated with a significant shift in the hydrated density distributions of LDL in the diabetic groups, with the average peak densities being 1.0320 g/mL (in C), 1.0365 g/mL (in D), and 1.0380 g/mL (in T) (p<.05). The LDL particles were also smaller in the NIDDM patients: 21.1±0.7, 20.4±0.5, and 20.6±0.5 nm in C, D, and T groups, respectively (p<.05). When the NIDDM groups were analyzed together, the LDL peak density was found to correlate with both insulin resistance (measured by a modified Harano technique; r=0-37, /><.O15) and total triglyceride concentrations (r=0.40,P<.0l). The results show that diabetic patients have small, dense LDL particles, which may be related to insulin resistance, and that these occur with minimal elevations of total triglyceride concentrations. These potentially atherogenic changes may contribute to the increased coronary heart disease in diabetic patients with mild hyperlipidemia.