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These abnormalities may contribute to residual CVD risk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>To investigate the kinetics of ApoB-48- and ApoB-100-containing lipoproteins, we performed a secondary analysis of 11 overweight\/obese individuals with type 2 diabetes who were treated with lifestyle counselling and on a stable dose of metformin who were from an earlier clinical study, and compared these with 11 control participants frequency-matched for age, BMI and sex. Participants in both groups were on a similar statin regimen during the study. Stable isotope tracers were used to determine the kinetics of the following in response to a standard fat-rich meal: (1) apolipoprotein (Apo)B-48 in chylomicrons and VLDL; (2) ApoB-100 in VLDL, intermediate-density lipoprotein (IDL) and LDL; and (3) triglyceride (TG) in VLDL.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The fasting lipid profile did not differ significantly between the two groups. Compared with control participants, in individuals with type 2 diabetes, chylomicron TG and ApoB-48 levels exhibited an approximately twofold higher response to the fat-rich meal, and a twofold higher increment was observed in ApoB-48 particles in the VLDL<jats:sub>1<\/jats:sub> and VLDL<jats:sub>2<\/jats:sub> density ranges (all <jats:italic>p\u00a0<\/jats:italic>&lt; 0.05). Again comparing control participants with individuals with type 2 diabetes, in the latter, total ApoB-48 production was 25% higher (556 \u00b1 57 vs 446 \u00b1 57 mg\/day; <jats:italic>p\u00a0<\/jats:italic>&lt; 0.001), conversion (fractional transfer rate) of chylomicrons to VLDL was around 40% lower (35 \u00b1 25 vs 82 \u00b1 58 pools\/day; <jats:italic>p<\/jats:italic>=0.034) and direct clearance of chylomicrons was 5.6-fold higher (5.6 \u00b1 2.2 vs 1.0 \u00b1 1.8 pools\/day; <jats:italic>p\u00a0<\/jats:italic>&lt; 0.001). During the postprandial period, ApoB-48 particles accounted for a higher proportion of total VLDL in individuals with type 2 diabetes (44%) compared with control participants (25%), and these ApoB-48 VLDL particles exhibited a fivefold longer residence time in the circulation (<jats:italic>p\u00a0<\/jats:italic>&lt; 0.01). No between-group differences were seen in the kinetics of ApoB-100 and TG in VLDL, or in LDL ApoB-100 production, pool size and clearance rate. As compared with control participants, the IDL ApoB-100 pool in individuals with type 2 diabetes was higher due to increased conversion from VLDL<jats:sub>2<\/jats:sub>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>Abnormalities in the metabolism of intestinally derived ApoB-48-containing lipoproteins in individuals with type 2 diabetes on statins may help to explain the residual risk of CVD and may be suitable targets for interventions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov NCT02948777.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-023-06008-0","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T19:01:37Z","timestamp":1696014097000},"page":"2307-2319","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Contribution of intestinal triglyceride-rich lipoproteins to residual atherosclerotic cardiovascular disease risk in individuals with type 2 diabetes on statin therapy"],"prefix":"10.1007","volume":"66","author":[{"given":"Marja-Riitta","family":"Taskinen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niina","family":"Matikainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Bj\u00f6rnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanni","family":"S\u00f6derlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Inkeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hakkarainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helka","family":"Parviainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Sihlbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Thorsell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Adiels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J.","family":"Packard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-8091","authenticated-orcid":false,"given":"Jan","family":"Bor\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,29]]},"reference":[{"issue":"1","key":"6008_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","volume":"41","author":"F Mach","year":"2020","unstructured":"Mach F, Baigent C, Catapano AL et al (2020) 2019 ESC\/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. 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Perttunen\u2010Nio and J. Haapaniemi (University of Helsinki, Helsinki, Finland) and E. Hedman Sabler and K. Sk\u00e5l\u00e9n (University of Gothenburg, Gothenburg, Sweden) for excellent laboratory work and patient care.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Data are available on a population basis but not on an individual level. This requirement is a condition of the ethical permission for the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This project was funded by grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement, the Novo Nordisk Foundation, the Sigrid Juselius Foundation, Helsinki University Hospital Government Research funds, the Finnish Heart Foundation, the Finnish Diabetes Research Foundation and Diabetes Wellness.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"CJP reports honoraria and grants from Amgen, Amarin, MSD, Pfizer, Novartis and Response Therapeutics. JB reports honoraria and grants from Pfizer, Novartis, Akcea, Amgen and NovoNordisk. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"M-RT, NM and JB contributed to conception and design of this study. NM, EB, JI, SS, AH, HP, CS, AT, LA and MA contributed to the acquisition of data or analysis. M-RT, NM, EB, MA, CJP and JB contributed to the interpretation of data. M-RT, CJP and JB drafted the original and revised manuscripts. All authors have reviewed the manuscript critically for important intellectual content, and approved the final version of the manuscript to be published. JB and M-RT are responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}