{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:22Z","timestamp":1787029282680,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["2 I01 BX004774-05"],"award-info":[{"award-number":["2 I01 BX004774-05"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Ileitis, or inflammation of the terminal ileum, is often linked to inflammatory bowel disease (IBD), especially Crohn\u2019s disease, but may also arise from non-steroidal anti-inflammatory drug (NSAID) use. While NSAIDs are known to cause gastrointestinal injury, their role in ileitis and downstream metabolic consequences remains unclear. This study evaluated the relationship between NSAID use, biopsy-confirmed ileitis, and glucose metabolism abnormalities in patients with and without IBD. Methods: We conducted a retrospective cohort study of 3725 adults who underwent ileal biopsy between 2009 and 2022 at a tertiary care center. Patients were stratified based on histologic evidence of ileitis. Collected data included demographics, IBD status, NSAID and steroid use, hemoglobin A1C, fasting glucose, and diagnoses of abnormal glucose metabolism. Multivariable logistic and linear regression models adjusted for age, BMI, sex, steroid use, and IBD. Results: Of 3725 patients, 876 had biopsy-confirmed ileitis. NSAID use\u2014categorized as current, historical, or inpatient\u2014was not significantly associated with ileitis after adjustment. In contrast, IBD was the strongest independent predictor (p &lt; 0.05). Although unadjusted analyses showed lower A1C in the ileitis group (p = 0.003), this was not significant after controlling for confounders (p = 0.084). No significant associations were found between ileitis and fasting glucose or abnormal glucose metabolism. Age and BMI were the dominant predictors of glycemic abnormalities. Conclusions: NSAID use was not associated with biopsy-confirmed ileitis or impaired glucose metabolism. Traditional metabolic risk factors were stronger predictors of glycemic abnormalities than localized ileal inflammation.<\/jats:p>","DOI":"10.3390\/nu17091514","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:05:57Z","timestamp":1745989557000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NSAIDs, Ileal Inflammation, and Glucose Metabolism: Insights from a Large Retrospective Cohort"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5962-885X","authenticated-orcid":false,"given":"Stephanie Hosanna","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles Jadd","family":"Hoilat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Division of Gastroenterology and Hepatology, University of Iowa Hospitals & Clinics, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikash","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Gonzalez Bravo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52246, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-6234","authenticated-orcid":false,"given":"Marcelo L. G.","family":"Correia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Division of Endocrinology and Metabolism, University of Iowa Hospitals & Clinics, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-580X","authenticated-orcid":false,"given":"Mohamad","family":"Mokadem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Division of Gastroenterology and Hepatology, University of Iowa Hospitals & Clinics, Iowa City, IA 52242, USA"},{"name":"Iowa City VA Health Care System, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s11894-010-0112-5","article-title":"Ileitis: When It Is Not Crohn\u2019s Disease","volume":"12","author":"DiLauro","year":"2010","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ajg.2014.114","article-title":"Terminal ileitis found upon imaging: Is it always Crohn\u2019s disease?","volume":"109","author":"Pais","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4647","DOI":"10.3748\/wjg.v17.i42.4647","article-title":"Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury","volume":"17","author":"Park","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1056\/NEJM199209103271101","article-title":"Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs","volume":"327","author":"Allison","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_5","unstructured":"Ghlichloo, I., and Gerriets, V. (2024). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.5152\/eurasianjmed.2018.0010","article-title":"Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level","volume":"50","author":"Gunaydin","year":"2018","journal-title":"Eurasian J. Med."},{"key":"ref_7","first-page":"253","article-title":"Nonsteroidal antiinflammatory drugs and the small intestine","volume":"6","author":"Fortun","year":"2007","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1177\/10668969221076549","article-title":"Comprehensive evaluation and unique morphologic features of nonsteroidal anti-inflammatory drug (NSAID) enteropathy in the terminal ileum","volume":"30","author":"Nguyen","year":"2022","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.cgh.2008.06.021","article-title":"Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: A pilot study","volume":"6","author":"Watanabe","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1007\/s00535-009-0102-2","article-title":"Present status and strategy of NSAIDs-induced small bowel injury","volume":"44","author":"Higuchi","year":"2009","journal-title":"J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1053\/j.gastro.2005.03.020","article-title":"A quantitative analysis of nsaid-induced small bowel pathology by capsule enteroscopy","volume":"128","author":"Maiden","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1055\/s-2007-966925","article-title":"Capsule endoscopy","volume":"39","author":"Saurin","year":"2007","journal-title":"Endoscopy"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hanselman, E.C., Harmon, C.P., Deng, D., Sywanycz, S.M., Caronia, L., Jiang, P., and Breslin, P.A.S. (2025). Ibuprofen inhibits human sweet taste and glucose detection implicating an additional mechanism of metabolic disease risk reduction. Br. J. Pharmacol.","DOI":"10.1111\/bph.70004"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1002\/phar.1483","article-title":"Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide","volume":"34","author":"Moore","year":"2014","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e001001","DOI":"10.1161\/JAHA.114.001001","article-title":"Effect of phosphodiesterase inhibition on insulin resistance in obese individuals","volume":"3","author":"Ho","year":"2014","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.14309\/ajg.0000000000001932","article-title":"The association between nonsteroidal anti-inflammatory drug use and inflammatory bowel disease exacerbations: A true association or residual bias?","volume":"117","author":"Van","year":"2022","journal-title":"Off. J. Am. Coll. Gastroenterol.|ACG"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/S1542-3565(03)70031-7","article-title":"Ulcerative ileitis encountered at ileo-colonoscopy: Likely role of nonsteroidal agents","volume":"1","author":"Lengeling","year":"2003","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, M., Xia, F., Xia, S., Zhou, W., Zhang, Y., Han, X., Zhao, K., Feng, L., Dong, R., and Tian, D. (2022). NSAID-associated small intestinal injury: An overview from animal model development to pathogenesis, treatment, and prevention. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.818877"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.mayocp.2017.04.010","article-title":"Crohn disease: Epidemiology, diagnosis, and management","volume":"92","author":"Feuerstein","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Herz, H., Song, Y., Ye, Y., Tian, L., Linden, B., Abu El Haija, M., Chu, Y., Grobe, J.L., Lengeling, R.W., and Mokadem, M. (2021). Nsaid-induced enteropathy affects regulation of hepatic glucose production by decreasing glp-1 secretion. Nutrients, 14.","DOI":"10.3390\/nu14010120"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"352","DOI":"10.2337\/db08-0875","article-title":"Exenatide sensitizes insulin-mediated whole-body glucose disposal and promotes uptake of exogenous glucose by the liver","volume":"58","author":"Zheng","year":"2009","journal-title":"Diabetes"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/9\/1514\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:24:26Z","timestamp":1760030666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/9\/1514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["nu17091514"],"URL":"https:\/\/doi.org\/10.3390\/nu17091514","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}