Significant improvement of apolipoprotein B-containing lipoprotein metabolism by insulin treatment in patients with non-insulin-dependent diabetes mellitus.
OBJECTIVE
Patients with Type II (non-insulin-dependent) diabetes mellitus have multiple abnormalities in apolipoprotein B (apoB)-containing lipoprotein metabolism. These abnormalities are likely to play an important part in the development of premature atherogenesis in these patients. This stable 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-[1-13C] leucine, we studied apoB metabolism in five control subjects without insulin resistance and in six poorly controlled Type II diabetic patients before and 2 months after the introduction of insulin therapy.


RESULTS
Insulin treatment induced a decrease of very low density lipoprotein 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 density lipoprotein [0.20 +/- 0.08 vs 0.14 +/- 0.07 pool.h-1, p < 0.05 (control subjects: 0.36 +/- 0.10)]. On the other hand, insulin treatment induced an acceleration of intermediate density lipoprotein apoB turn-over without changing its plasma concentration [77 +/- 37 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 lipoprotein 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 constant low density lipoprotein apoB plasma concentration [965 +/- 485 vs 984 +/- 558 mg.l-1 (control subjects: 699 +/- 106)].


CONCLUSIONS
Insulin treatment in Type II diabetes induces profound metabolic modifications of lipoprotein, resulting in significant decrease of the intravascular residence time of very low density lipoprotein, intermediate density lipoprotein and low density lipoprotein particles. This is likely to make these particles less harmful.
Duvillard
L
L
INSERM U 498, Faculty of Medicine, Dijon, France.
Pont
F
F
Florentin
E
E
Gambert
P
P
Vergès
B
B
D001055:Apolipoproteins B / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012016:Reference Values; D012984:Software; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D001786:Blood Glucose; D002247:Carbon Isotopes; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D007328:Insulin; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D007930:Leucine