Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes

Objective: Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels triglyceride-rich lipoproteins and their remnants. The metabolic effects PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers. Approach Results: Triglyceride transport the metabolism apos (apolipoproteins) B48, B100, C-III, E after a fat-rich meal before evolocumab treatment 13 diabetes. Kinetic parameters determined for following: apoB48 chylomicrons; triglyceride VLDL 1 (very low-density lipoprotein) ; apoB100 , IDL (intermediate-density lipoprotein), LDL (low-density lipoprotein). Evolocumab did not alter kinetics chylomicrons or . In contrast, fractional catabolic rates -apoB100 -triglyceride both increased by about 45%, which led 28% fall plasma level. LDL-apoB100 was markedly reduced evolocumab, heterogeneity fraction. clearance more rapidly metabolized 61% decreased production slowly cleared 75%. ApoC-III altered but apoE 45% level fell 33%. associated decrease - IDL-apoB100 concentrations. Conclusions: had only minor that are involved (chylomicrons ) but, profound impact carry cholesterol (VLDL IDL, LDL). Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT02948777.