Significant improvement of apolipoprotein B-containing lipoprotein metabolism by insulin treatment in patients with non-insulin-dependent diabetes mellitus

Aims/hypothesis. Patients with Type II (non-insulin-dependent) diabetes mel litus have multiple abnormalities in apolipoprotein B (apoB)-containing lip oprotein metabolism. These abnormalities are likely to play an important pa rt in the development of premature atherogenesis in these patients. This st able isotope kinetic experiment was designed to study the effect of insulin therapy on apoB metabolism in poorly controlled Type II diabetic patients. Methods. Using L-[1-C-13] leucine, we studied apoB metabolism in five contr ol subjects without insulin resistance and in six poorly controlled Type II diabetic patients before and 2 months after the introduction of insulin th erapy. Results. Insulin treatment induced a decrease of very low density lipoprote in apoB plasma concentration [121 +/- 42 vs 158 +/- 91 mg . l(-1), p < 0.05 (control subjects: 48 +/- 20)], related to an increased catabolism of very low density lipoprotein towards intermediate density lipoprotein or low de nsity lipoprotein [0.20 +/- 0.08 vs 0.14 +/- 0.07 pool . h(-1), p < 0.05 (c ontrol subjects: 0.36 +/- 0.10)]. On the other hand, insulin treatment indu ced an acceleration of intermediate density lipoprotein apoB turn-over with out changing its plasma concentration [77 +/- 39 vs 61 +/- 18 mg . l(-1), ( control subjects: 17 +/- 3)], by increasing both its production rate [22.6 +/- 9.2 vs 18.2 +/- 9.6 mg . l(-1) . h(-1), p < 0.05 (control subjects: 18. 4 +/- 3.2)] and its catabolic rate towards low density lipoprotein [0.34 +/ - 0.22 vs 0.22 +/- 0.16 pool . h(-1), p < 0.05 (control subjects: 1.02 +/- 0.13)]. Likewise, insulin treatment increased low density lipoprotein apoB production rate [20.2 +/- 7.4 vs 16.9 +/- 7.7 mg . l(-1) . h(-1), p < 0.05 (control subjects: 16.9 +/- 2.3)] and restored a normal low density lipopro tein apoB fractional catabolic rate [0.022 +/- 0.004 vs 0.018+/- 0.004 pool . h(-1), p < 0.05 (control subjects: 0.025 +/- 0.004)], resulting in a con stant low density lipoprotein apoB plasma concentration [965 +/- 485 vs 984 +/- 558 mg . l(-1) (control subjects: 699 +/- 106)]. Conclusion/interpretation. Insulin treatment in Type II diabetes induces pr ofound metabolic modifications of lipoprotein, resulting in significant dec rease of the intravascular residence time of very low density lipoprotein, intermediate density lipoprotein and low density lipoprotein particles. Thi s is likely to make these particles less harmful.