Effect of acute exogenous hyperinsulinaemia on very low density lipoprotein subfraction composition in normal subjects

Background Subtle abnormalities of very-low-density lipoprotein (VLDL) comp osition and distribution seem to be associated with increased cardiovascula r risk. The aims of this study were first, to evaluate whether hyperinsulin aemia per se is able to produce VLDL abnormalities and second, whether this occurs through a stimulation of lipolytic enzymes. Materials and methods Eight normal male volunteers, age 36 +/- 7 years (M /- SD), body mass index (BMI) 26+/-3 kg m(-2), underwent a 5-h euglycaemic hyperinsulinaemic clamp (1.2 mU insulin/kg b.w. min(-1)). Nine sex, age and BMI comparable subjects underwent control experiments (saline infusion). T hree VLDL subfractions of decreasing size were isolated by density gradient ultracentrifugation; lipoprotein lipase (LPL) and hepatic lipase (HL) post -heparin plasma activities were determined by the H-3-labelled triolein met hod. Results Hyperinsulinaemia (similar to 65 mU mL(-1)) produced the expected p lasma free fatty acid suppression. Triglyceride levels were reduced in tota l VLDL (- 27 +/- 32% vs. + 38 +/- 52% after saline, P < 0.05) and in the la rger VLDL (- 56 +/- 19 vs. + 34 +/- 38, P < 0.001). Moreover the relative c ontribution of the larger subfraction was decreased (- 39 +/- 15% vs. - 3 /- 21%, P < 0.01), while the percentage of smaller particles was increased (+ 17 +/- 20 vs. - 9 +/- 22, P < 0.05). LPL and HL activities were decrease d to the same degree during either insulin or saline infusion. Conclusions Exogenous hyperinsulinaemia produced lipoprotein abnormalities partially similar to those previously shown in type 1 diabetic patients, in dicating that these abnormalities may be secondary to insulin therapy.