{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:47:03Z","timestamp":1792860423932,"version":"4.5.0"},"reference-count":69,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels of triglyceride-rich lipoproteins and their remnants. The metabolic effects of PCSK9 (proprotein convertase subtilisin\/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              Triglyceride transport and the metabolism of apos (apolipoproteins) B48, B100, C-III, and E after a fat-rich meal were investigated before and on evolocumab treatment in 13 subjects with type 2 diabetes. Kinetic parameters were determined for the following: apoB48 in chylomicrons; triglyceride in VLDL\n              <jats:sub>1<\/jats:sub>\n              (very low-density lipoprotein) and VLDL\n              <jats:sub>2<\/jats:sub>\n              ; and apoB100 in VLDL\n              <jats:sub>1<\/jats:sub>\n              , VLDL\n              <jats:sub>2<\/jats:sub>\n              , IDL (intermediate-density lipoprotein), and LDL (low-density lipoprotein). Evolocumab did not alter the kinetics of apoB48 in chylomicrons or apoB100 or triglyceride in VLDL\n              <jats:sub>1<\/jats:sub>\n              . In contrast, the fractional catabolic rates of VLDL\n              <jats:sub>2<\/jats:sub>\n              -apoB100 and VLDL\n              <jats:sub>2<\/jats:sub>\n              -triglyceride were both increased by about 45%, which led to a 28% fall in the VLDL\n              <jats:sub>2<\/jats:sub>\n              plasma level. LDL-apoB100 was markedly reduced by evolocumab, which was linked to metabolic heterogeneity in this fraction. Evolocumab increased clearance of the more rapidly metabolized LDL by 61% and decreased production of the more slowly cleared LDL by 75%. ApoC-III kinetics were not altered by evolocumab, but the apoE fractional catabolic rates increased by 45% and the apoE plasma level fell by 33%. The apoE fractional catabolic rates was associated with the decrease in VLDL\n              <jats:sub>2<\/jats:sub>\n              - and IDL-apoB100 concentrations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Evolocumab had only minor effects on lipoproteins that are involved in triglyceride transport (chylomicrons and VLDL\n              <jats:sub>1<\/jats:sub>\n              ) but, in contrast, had a profound impact on lipoproteins that carry cholesterol (VLDL\n              <jats:sub>2<\/jats:sub>\n              , IDL, LDL).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT02948777.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315446","type":"journal-article","created":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T10:02:42Z","timestamp":1608804162000},"page":"962-975","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes"],"prefix":"10.1161","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct02948777","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Marja-Riitta","family":"Taskinen","sequence":"first","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine (M.-R.T., J.K., S.S., N.M., K.P., M. 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Ainola), University of Helsinki, Finland."},{"name":"Department of Endocrinology, Abdominal Center (S.S., N.M.), Helsinki University Hospital, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0041-1240","authenticated-orcid":true,"given":"Niina","family":"Matikainen","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine (M.-R.T., J.K., S.S., N.M., K.P., M. Ainola), University of Helsinki, Finland."},{"name":"Department of Endocrinology, Abdominal Center (S.S., N.M.), Helsinki University Hospital, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-2319","authenticated-orcid":true,"given":"Kimmo","family":"Porthan","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, Faculty of Medicine (M.-R.T., J.K., S.S., N.M., K.P., M. 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