{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:46:48Z","timestamp":1782902808880,"version":"3.54.5"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Clin. Diabetes Healthc."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR\u03b1) modulator, lowers triglycerides and improves lipid parameters. However, its effects on oxidized LDL-related markers, including malondialdehyde-modified low-density lipoprotein (MDA-LDL), and associated\n                      <jats:italic>in vivo<\/jats:italic>\n                      gene-expression changes in humans remain limited. In addition, whether pemafibrate-associated changes in oxidized LDL-related biomarkers have clinical implications for atherosclerotic progression or cardiovascular risk remains uncertain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prespecified subanalysis of the randomized, open-label, parallel-group PARADISE in Kagoshima study, 51 participants assigned to pemafibrate and 46 assigned to eicosapentaenoic acid (EPA) were included in the clinical analysis. All participants had type 2 diabetes and hypertriglyceridemia and received treatment for 16 weeks. We evaluated changes in MDA-LDL, lipoprotein fractions including small dense LDL-related fractions, and exploratory peripheral blood mononuclear cell (PBMC) gene expression. PBMC gene expression was assessed in 11 participants in the Pemafibrate group and 7 in the EPA group, and was considered exploratory and hypothesis-generating.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with EPA, pemafibrate produced a significantly greater reduction in triglycerides (least-squares mean difference, \u221279.2 mg\/dL; 95% confidence interval [CI], \u2212117 to \u221241.5; P &amp;lt; 0.001), and a greater increase in HDL-C (4.64 mg\/dL; 95% CI, 2.43 to 6.84; P &amp;lt; 0.001). The mean change in MDA-LDL from baseline to week 16 was \u221230.3 \u00b1 32.4 U\/L in the Pemafibrate group and \u22129.2 \u00b1 44.3 U\/L in the EPA group, yielding a least-squares mean difference of \u221221.2 U\/L (95% CI, \u221236.9 to \u22125.4; P\u00a0=\u00a00.009). In the exploratory PBMC analysis, ABCA1 and LCAT remained significant after false discovery rate adjustment, whereas other genes showed only nominal differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pemafibrate was associated with greater 16-week reductions in MDA-LDL and small dense LDL fractions than EPA in patients with type 2 diabetes and hypertriglyceridemia. These findings suggest modification of selected lipid-quality biomarkers. Their clinical relevance remains to be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcdhc.2026.1850470","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:13:01Z","timestamp":1782900781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pemafibrate is associated with greater reductions in MDA-LDL and small dense LDL fractions with exploratory PBMC gene-expression changes: a prespecified subanalysis of the PARADISE in Kagoshima study"],"prefix":"10.3389","volume":"7","author":[{"given":"Toru","family":"Kubo","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Deguchi","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Shinnakasu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Izuro Imamura Hospital","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kawade","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, 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Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrine Medicine, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]},{"name":"National Hospital Organization Kagoshima Medical Center","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2005.01.005","article-title":"Regulation of plasma triglycerides in insulin resistance and diabetes","volume":"36","author":"Ginsberg","year":"2005","journal-title":"Arch Med Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12933-019-0851-z","article-title":"Serum triglycerides as a risk factor for cardiovascular diseases in type 2 diabetes mellitus: a systematic review and 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