The ability of intensive insulin treatment to increase plasma high density lipoprotein (HDL)-cholesterol levels was evaluated in 12 patients with noninsulin-dependent diabetes mellitus. Patients were treated for 6 weeks with one daily morning injection of ultralente insulin, in combination with administration of regular insulin before breakfast, lunch, and dinner. The mean (+/- SEM) fasting plasma glucose concentration fell from 289 +/- 21 to 122 +/- 9 mg/dl (P less than 0.001), and the mean hourly postprandial glucose concentration fell from 313 +/- 24 to 102 +/- 7 mg/dl (P less than 0.001). In addition, insulin treatment was associated with a reduction in both fasting plasma triglyceride (256 +/- 45 to 137 +/- 18 mg/dl; P less than 0.001) and cholesterol (224 +/- 25 to 199 +/- 19 mg/dl; P less than 0.05) concentrations. However, plasma HDL-cholesterol concentrations, which were low to begin with, did not rise in association with excellent glycemic control. These results demonstrate that hyperglycemia and hypertriglyceridemia can be effectively reduced by an aggressive program of insulin treatment in patients with noninsulin-dependent diabetes mellitus, but this intervention need not lead to an improvement in the abnormal HDL-cholesterol metabolism in these patients.