Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia
Journal article, 2005
OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS AND RESULTS: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by diabetes per se. The production rates of VLDL1 apoB and TG were closely related, as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized particles was very similar in the 2 groups. Plasma glucose, insulin, and free fatty acids together explained 55% of the variation in VLDL1 TG production rate. CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic production of VLDL1 particles similar in size and composition to those in nondiabetic subjects. We propose that hyperglycemia is the driving force that aggravates overproduction of VLDL1 in DM2.
Cholesterol
Deuterium/diagnostic use
Glycerol/pharmacokinetics
Blood Glucose
Hyperglycemia/complications/*metabolism
Insulin Resistance
Male
Dyslipidemias/complications/*metabolism
Type 2/complications/*metabolism
HDL/blood
Leucine/pharmacokinetics
Triglycerides/blood
Adult
Diabetes Mellitus
Apolipoproteins B/blood
Cholesterol
VLDL/*biosynthesis/*blood
Humans
Author
Martin Adiels
Chalmers, Mathematical Sciences
University of Gothenburg
Jan Borén
University of Gothenburg
M. J. Caslake
Helsinki University Central Hospital
P. Stewart
Helsinki University Central Hospital
Aina Soro
Glasgow Royal Infirmary
J. Westerbacka
Glasgow Royal Infirmary
Bernt Wennberg
Chalmers, Mathematical Sciences, Mathematics
University of Gothenburg
Sven-Olof Olofsson
University of Gothenburg
C. Packard
Helsinki University Central Hospital
M. R. Taskinen
Glasgow Royal Infirmary
Arteriosclerosis, Thrombosis, and Vascular Biology
1079-5642 (ISSN) 1524-4636 (eISSN)
Vol. 25 8 1697-703Subject Categories
Dermatology and Venereal Diseases
Computational Mathematics
DOI
10.1161/01.ATV.0000172689.53992.25