{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:49:25Z","timestamp":1791434965542,"version":"4.3.3"},"reference-count":60,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2DM), driven in part by oxidative stress and the accumulation of advanced glycation end products (AGEs). Oleanolic acid (OA), a natural triterpene present in olive\u2010derived matrices, may modulate AGE metabolism. In this prespecified, exploratory secondary analysis of the OLTRAD trial, we evaluated whether long\u2010term intake of OA\u2010enriched olive oil attenuates kidney function decline in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the OLTRAD randomised controlled trial, 97 patients with T2DM were assigned to consume OA\u2010enriched olive oil (600\u2009mg OA\/kg) or control olive oil for 12\u2009months, alongside standard therapy. Kidney outcomes included estimated glomerular filtration rate (eGFR) and urinary albumin\u2010to\u2010creatinine ratio (uACR). Circulating AGEs (methylglyoxal [MG], carboxymethyllysine [CML]), enzymes involved in AGE metabolism (aldose reductase [AR], glyoxalase\u2010I [GloxI]), and oxidative stress markers (ROS and MDA) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      OA\u2010enriched olive oil attenuated eGFR decline relative to control, an effect restricted to participants with mildly impaired eGFR at baseline (60\u201390\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ; time\u2009\u00d7\u2009group interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010), with no significant interaction among participants with normal baseline eGFR. OA\u2010enriched oil also prevented the rise in uACR observed with control oil. Mechanistically, OA reduced AR concentration and increased GloxI activity, resulting in lower circulating MG, whereas CML remained unchanged. OA\u2010enriched oil further reduced ROS and MDA levels, while MDA increased with control oil.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this exploratory, hypothesis\u2010generating secondary analysis, long\u2010term consumption of OA\u2010enriched olive oil was associated with attenuated kidney function decline in patients with T2DM, an effect limited to those with baseline mildly impaired eGFR. These changes were associated with modulation of AGE\u2010related pathways and reduced oxidative stress. As the trial was powered for glycemic control rather than renal outcomes, larger, adequately powered studies are needed to confirm these findings before their clinical relevance can be established.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                      identifier: NCT06030544;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06030544\">https:\/\/clinicaltrials.gov\/study\/NCT06030544<\/jats:ext-link>\n                    <\/jats:p>\n                  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