{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:26:59Z","timestamp":1793626019584,"version":"4.5.1"},"reference-count":151,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders arising from decreased insulin secretion and insulin sensitivity. Patients with T2DM take statins to prevent diabetic complications and mitigate mortality risk associated with this disease. Statins primarily function by blocking HMG\u2010CoA, resulting in reduced cholesterol levels. Statins have been suggested to possess certain antidiabetic properties. However, the overall effects of statins remain controversial. The aim of this study was to investigate the mechanisms and triggering conditions for the development of statin\u2010induced T2DM, despite their reported pleiotropic antidiabetic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This paper is a narrative review. A thorough literature search was carried out across PubMed, Scopus and Google Scholar to identify studies relevant to the evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the cholesterol biosynthesis pathway (the mevalonate pathway), in addition to cholesterol, isoprenoids such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate are also produced. Inhibition of these metabolites largely mediates the diabetogenic action of statins. The effects of statins on insulin secretion appear to be largely independent of cholesterol. However, the inhibition of cholesterol synthesis in pancreatic beta cells reduces insulin secretion through impaired function of SNARE proteins and calcium channels. The most prominent effects of statins on insulin secretion and sensitivity are attributed to the suppression of isoprenoids, particularly Cdc42, Rac1 and Rab. Furthermore, studies have shown that statins directly affect the levels of some insulin\u2010sensitivity\u2010related factors, independent of the identification of isoprenoid\u2010mediated pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Atorvastatin, simvastatin and rosuvastatin possess the most pronounced diabetogenic properties. In contrast, lovastatin, fluvastatin, pitavastatin and most notably pravastatin exert either neutral or advantageous effects with respect to glucose metabolism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70305","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T11:47:42Z","timestamp":1786535262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms and Predisposing Conditions for Statin\u2010Induced New\u2010Onset Type 2 Diabetes Mellitus: A Paradox Relative to Their Pleiotropic Metabolic Effects"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8699-4688","authenticated-orcid":false,"given":"Ali Nosrati","family":"Andevari","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Afzalipour Faculty of Medicine Kerman University of Medical Sciences  Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-2660","authenticated-orcid":false,"given":"Mohsen","family":"Koolivand","sequence":"additional","affiliation":[{"name":"Royan Stem Cell Technology Company  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","first-page":"68","article-title":"Dipeptidyl Peptidase\u20104 Inhibitors in Type 2 Diabetes Mellitus: Mechanisms and Efficacy in Clinical Practice","volume":"18","author":"Nosrati Andevari A.","year":"2026","journal-title":"IJDO"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"69","article-title":"Beyond Glycemia: Metformin's Anti\u2010Inflammatory, Antioxidant, and Immunomodulatory Effects in Chronic Diseases: A Narrative Review","volume":"13","author":"Nosrati Andevari A.","year":"2026","journal-title":"Reviews in Clinical Medicine"},{"key":"e_1_2_11_4_1","volume-title":"Prevalence of Type 2 Diabetes Mellitus Complications in Human: Chattogram Veterinary & Animal","author":"Alam M. 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