Association of Frail Status with Incident Digestive Diseases: A Large Prospective Cohort Study

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.

Leveraging two prospective cohorts from the UK Biobank (n ≈ 340,000 and n ≈ 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.

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]: 1.57-1.72) for overall GID and 1.78 (95% CI: 1.66-1.92) 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 <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.

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.