Overproduction of VLDL 1 Driven by Hyperglycemia Is a Dominant Feature of Diabetic Dyslipidemia

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Abstract
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... Analysis of the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes and healthy controls revealed that type 2 diabetes and insulin resistance are associated with excess hepatic production of VLDL1 particles similar in size and composition to those of nondiabetic subjects.