The Effect of Continuous Subcutaneous Insulin Infusion on Very-Low-Density Lipoprotein Triglyceride Metabolism in Type I Diabetes Mellitus

Abstract

The effect of continuous subcutaneous insulin infusion (CSII) on very-low-density lipoprotein triglyceride (VLDL-TG) metabolism was studied in seven normolipidemic type I diabetic patients. VLDL-TG transport was determined using 3H-glycerol as an endogenous precursor of VLDL-TG, and the resultant turnover curves were evaluated by multicompartmental analysis. Kinetic studies were performed in the diabetic patients during conventional insulin therapy and again after 3 wk of euglycemia achieved with CSII, and the results were compared with those obtained in 5 age-, weight-, and sex-matched normolipidemic nondiabetic subjects. After 3 wk of CSII, the mean (± SEM) 24-h plasma glucose levels in the diabetic patients decreased from 238 ±15 mg/dl on conventional therapy to 99 ± 11 mg/dl (P < 0.05) on CSII therapy. The total glycosylated hemoglobin levels decreased from 10.2 ± 0.5 to 6.5 ± 0.4%. There was a significant decrease in fasting plasma cholesterol (172 ± 13 mg/dl to 136 ± 4 mg/dl), LDL cholesterol (104 ± 9 mg/dl to 82 ± 4 mg/dl), plasma triglyceride (114 ± 24 mg/dl to 71 ± 9 mg/dl), and VLDL-TG (68 ± 18 mg/dl to 37 ± 5 mg/dl) levels. There was no change in the HDL cholesterol concentration. Results of the kinetic studies in the conventionally treated diabetic patients revealed normal VLDL-TG transport rates and fractional catabolic rates (FCR). CSII caused a marked and significant fall in mean VLDL-TG transport rates (12.2 ± 3.5 to 4.1 ± 0.8 mg/h/kg IW, P < 0.05) to levels below those observed in the nondiabetic subjects (10.2 ± 2.1 mg/h/kg IW, P < 0.05). There was no change in the mean FCR with CSII. These data thus suggest that the mechanism responsible for the observed change in plasma triglyceride levels in normolipidemic type I diabetic patients that occurs with 3 wk of CSII treatment is due to suppression of hepatic VLDL-TG synthesis rather than the result of increased lipoprotein clearance.