To determine the acute effects of insulin on lipoprotein metabolism, we have followed the plasma lipoprotein lipid and apolipoprotein levels during insulin therapy for the first 24 hr in 13 patients with diabetic ketoacidosis. Corrections were made for plasma volume changes during treatment. Before insulin treatment, mean plasma triglyceride and cholesterol levels were 574 mg/dl (range 53-2355) and 212 mg/dl (range 118-416), respectively. Insulin therapy resulted in rapid decreases in triglyceride-rich lipoproteins, chylomicrons, and very low density lipoproteins (VLDL), with most patients achieving plasma triglyceride levels below 150 mg/dl at 24 hr. Mean basal levels of intermediate density lipoproteins (IDL) and low density lipoproteins (LDL)-cholesterol were low (9.9 and 72 mg/dl, respectively) and were statistically invariant with therapy. Mean basal levels of high density lipoprotein (HDL) cholesterol were also low (26 mg/dl, range 5-48) and were invariant during the first 12 hr and increased significantly to 29 mg/dl by the 24th hr. Plasma apoprotein (apo) B levels were in the upper normal range (101 mg/dl) before treatment and decreased with therapy due to significant decreases in VLDL, but not IDL or LDL apoB. VLDL appeared to have a normal apoprotein composition which did not change with treatment. Mean apoA-I levels which were near normal in plasma and HDL before therapy, decreased significantly (16%) by 12 hr and subsequently increased towards basal levels between 12 and 24 hr. The ratio of apoA-I to cholesterol in HDL also fell significantly during the entire 24 hr. Density gradient ultracentrifugal analysis of the d > 1.006 g/ml fractions indicated a selective decrease in "lighter" density fractions of HDL-apoA-I during treatment. These results provide evidence that insulin may decrease the secretion of apoA-I into plasma or increase catabolism.-Weidman, S. W., J. B. Ragland, J. N. Fisher, Jr., A. E. Kitabchi, and S. M. Sabesin. Effects of insulin on plasma lipoproteins in diabetic ketoacidosis: evidence for a change in high density lipoprotein composition composition during treatment.