{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:23:46Z","timestamp":1783527826088,"version":"3.55.0"},"reference-count":45,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dig Dis"],"abstract":"<jats:p>Introduction: Frailty, reflecting age-related decline in physiological reserve, has been implicated in adverse health outcomes, but its contribution to digestive disease risk is not well established. Methods: Leveraging two prospective cohorts from the UK Biobank (n \u2248 340,000 and n \u2248 358,000) with participants free of gastrointestinal diseases (GID) or hepatobiliary-pancreatic diseases (HBPD) at baseline, we evaluated incident disease over a median follow-up of 13.7 years using a validated frailty phenotype. Results: Individuals classified as frail showed consistently higher rates of digestive disorders than robust peers. After multivariable adjustment, hazard ratios (HRs) for frailty were 1.65 (95% confidence interval [CI]: 1.57\u20131.72) for overall GID and 1.78 (95% CI: 1.66\u20131.92) for HBPD. Risk elevations were observed for gastroesophageal reflux disease (HR: 1.70), peptic ulcer (HR: 1.81), inflammatory bowel disease (IBD) (HR: 1.48), irritable bowel syndrome (HR: 2.43), diverticulosis (HR: 1.38), constipation (HR: 2.25), coeliac disease (HR: 1.58), cirrhosis (HR: 2.22), metabolic dysfunction-associated steatotic liver disease (HR: 1.76), gallbladder disease (HR: 1.69), and pancreatic disease (HR: 1.60), all with p values of &lt;0.01. Subgroup analyses across age, sex, adiposity, and comorbidity strata yielded similar results. Exploratory mediation using the C-reactive protein-to-albumin ratio, an index of inflammation and nutritional status, suggested partial attenuation of the frailty-disease associations (up to 9.5% for IBD and 4.1% for cirrhosis). Excluding early events and adding extensive lifestyle and biochemical covariates did not materially change the findings. Conclusion: Frailty, including pre-frail states, appears to be an independent marker of vulnerability to a broad range of digestive diseases, supporting its potential use in early risk assessment and targeted preventive strategies.<\/jats:p>","DOI":"10.1159\/000552186","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T16:01:09Z","timestamp":1778169669000},"page":"1-10","source":"Crossref","is-referenced-by-count":0,"title":["Association of Frail Status with Incident Digestive Diseases: A Large Prospective Cohort 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