Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes

Abstract

To study the effects of rigorous insulin therapy on serum lipoproteins in patients with noninsulin-dependent diabetes not controlled with oral agents only, we measured serum lipoproteins, apoproteins, lipolytic enzymes, and glucose disposal using an insulin clamp technique before and after 4 weeks of insulin therapy. Lipoproteins were isolated by ultracentrifugation and high density lipoprotein (HDL) subfractions, by rate-zonal density gradient ultracentrifugation. The group included 11 women and eight men (age 58 ± 1 years and RBW 125 ± 4%). Body weight, glycosylated hemoglobin, mean diurnal glucose, plasma free insulin, and glucose uptake (M-value) were 75 vs. 76 kg; 11.9 vs 8.9%; 234 vs. 124 mg/dl; 12 vs. 27 μU/ml; and 5.0 ± 0.4 vs. 7.1 ± 0.6 mg/kg/min before and after insulin therapy, respectively. After insulin therapy there was a decrease of very low density lipoprotein (VLDL) triglyceride (-60%, p.< 0.001) but an increase of HDL2 cholesterol (+21%, p < 0.001); HDL2 phospholipids (+38%, p < 0.001); HDL2 proteins (+23%, p < 0.01); and HDL2 mass (127 ± 11 vs. 158 ± 12 mg/dl, p < 0.001). There was a decrease of HDL3 cholesterol (-13%, p < 0.05); HDL3 phospholipids (-16%, p < 0.05); HDL3 proteins (-18%, p < 0.001); and HDL3 mass (179 ± 6 vs. 146 ± 6, p < 0.01). Zonal profiles showed a redistribution of particles from HDL3 to HDL2. Serum apo A-I increased (p < 0.05), apo A-II remained constant, but apo B decreased (-29%, p < 0.001). The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p < 0.001). The changes of VLDL and HDL subfractions were not explained by respective changes of the blood glucose, free insulin, or M-value. The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.