{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:50:28Z","timestamp":1775868628373,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DA054992"],"award-info":[{"award-number":["R01DA054992"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY029799"],"award-info":[{"award-number":["R01EY029799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY031039"],"award-info":[{"award-number":["R01EY031039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG078892"],"award-info":[{"award-number":["R01AG078892"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG082108"],"award-info":[{"award-number":["R01AG082108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic inflammation is a key factor in type 2 diabetes mellitus (T2DM) development. The cholinergic anti\u2010inflammatory pathway (CAP) reduces inflammation by activating \u03b17 nicotinic acetylcholine receptors (\u03b17nAChRs) on macrophages, suppressing proinflammatory cytokines. Acetylcholinesterase inhibitors (AChEis), primarily used for Alzheimer's disease (AD), may exert anti\u2010inflammatory effects through the CAP. One AChEi, galantamine, also directly agonizes \u03b17nAChRs, potentially enhancing its anti\u2010inflammatory properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the association between AChEi use, particularly galantamine, and T2DM risk in AD patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of Veterans Health Administration (VA) data, examining early\u2010 and late\u2010onset AD patients receiving galantamine or other AD medications. Propensity score matching was used to balance groups and minimize confounding. Cox proportional hazard models assessed T2DM risk for galantamine, other AChEis and memantine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 40\u2009065\u2009AD patients were included in the study. Among early\u2010onset AD patients, galantamine use significantly reduced T2DM risk (hazard ratio [HR]\u2009=\u20090.80, 95% confidence interval [CI]: 0.66\u20130.98). Memantine also showed a protective effect (HR\u2009=\u20090.82, 95% CI: 0.69\u20131) in this group. Neither galantamine nor memantine influenced T2DM risk in late\u2010onset AD. Other AD medications showed no association with T2DM risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Galantamine use was associated with a lower risk of T2DM in early\u2010onset AD patients, potentially due to enhanced anti\u2010inflammatory effects through both AChE inhibition and direct \u03b17nAChR agonism. Memantine also demonstrated a protective effect. These findings suggest potential new applications for existing AD medications in T2DM prevention, particularly in early\u2010onset AD patients. Further research, including randomized controlled trials with diverse populations, is needed to confirm these results and the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16060","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T02:25:36Z","timestamp":1731378336000},"page":"675-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting the cholinergic anti\u2010inflammatory pathway for type 2 diabetes prevention: A retrospective cohort study"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-0097","authenticated-orcid":false,"given":"Joseph","family":"Magagnoli","sequence":"first","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy H.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Hardin","sequence":"additional","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Epidemiology &amp; Biostatistics University of South Carolina  Columbia South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayakrishna","family":"Ambati","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Ophthalmology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Pathology University of Virginia School of Medicine  Charlottesville Virginia USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology University of Virginia School of Medicine  Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Scott","family":"Sutton","sequence":"additional","affiliation":[{"name":"Dorn Research Institute Columbia VA Health Care System  Columbia South Carolina USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy University of South Carolina  Columbia South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665107005320"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.059"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135846"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/met.2004.2.82"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.1.42"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018528\u2010z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.06.031"},{"issue":"127","key":"e_1_2_9_9_1","first-page":"37","article-title":"Vagus nerve stimulation in brain diseases: therapeutic applications and biological mechanisms","volume":"2021","author":"Wang Y","year":"2020","journal-title":"Neurosci Biobehav Rev"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.04.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13288"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271537"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000500920"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1124"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1229"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80005-9"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2008.06.011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2003.11.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-200108001-00004"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00083"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134648"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201042665\u20102"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010\u20100855"},{"key":"e_1_2_9_25_1","first-page":"1","article-title":"Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy","volume":"00","author":"Moriguchi S","year":"2016","journal-title":"Mol Psychiatry"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104\u2010018\u20103715\u20109"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600\u20100404.2000.00310.x"},{"issue":"1","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0026-895X(25)08675-4","article-title":"Agonist responses of neuronal nicotinic acetylcholine receptors are potentiated by a novel class of allosterically acting ligands","volume":"49","author":"Schrattenholz A","year":"1996","journal-title":"Mol Pharmacol"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.12.1987"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.16060","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/full-xml\/10.1111\/dom.16060","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.16060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:53:31Z","timestamp":1775865211000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.16060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/dom.16060"],"URL":"https:\/\/doi.org\/10.1111\/dom.16060","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.16060\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16060\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16060\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16060\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16060\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16060\/v1\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]},"assertion":[{"value":"2024-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}