Diabetes as an Independent Risk Factor for Severe Inflammatory Bowel Disease: 1 Evidence from an Inflammation–Metabolism–Liver Coupling Framework

Bin Huang^1,2Honglin An¹Liming Chen³Yiman Qiu¹Yaping Su¹Shiju Shen⁴Huaping Wu¹Mengyuan Li¹Lisha Lu²Rong Wang^2*Hangju Hua^2*Wujin Chen^2*

• ¹Fujian University of Traditional Chinese Medicine, Fuzhou, China
• ²The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Fuzhou, China
• ³The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
• ⁴Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China

Background: The clinical course of inflammatory bowel disease (IBD) varies widely, 33 and identifying factors associated with severe disease is essential for risk stratification. 34 Diabetes has been proposed as a potential determinant of adverse outcomes, yet its 35 independent role in disease progression remains unclear. 36 Methods: We retrospectively analyzed clinical data from patients with mild and 37 severe IBD. Demographic, inflammatory, hepatic, and metabolic parameters were 38 compared between groups. Logistic regression was used to identify independent 39 predictors of severe IBD. Model performance was assessed using receiver operating 40 characteristic curves, calibration analysis, and cross-validation. An 41 inflammation–metabolism–liver coupling index (IMLCI) was constructed to integrate 42 key predictors. 43 Results: Patients with severe IBD exhibited significantly higher levels of 44 inflammatory markers (WBC, neutrophil percentage, CRP), impaired hepatic function 45 indices (ALT, AST, bilirubin), and adverse metabolic profiles (elevated TG and LDL, 46 reduced HDL and vitamin B12). Diabetes was strongly associated with severe IBD 47 (odds ratio = 3.81, P < 0.001), confirming its independent effect beyond traditional 48 risk factors. The inflammation–metabolism–liver coupling index (IMLCI) 49 demonstrated excellent discrimination (AUC = 0.900 in the training cohort and 0.891 50 in the testing cohort), good calibration (Hosmer–Lemeshow P = 0.83), and robust 51 internal validation, outperforming single laboratory or metabolic biomarkers. 52 Conclusion: Diabetes represents a strong independent risk factor for severe IBD. The 53 proposed IMLCI framework, integrating inflammation, metabolism, and liver 54 function, demonstrates high predictive accuracy and may provide a practical tool for 55 early identification and risk management of patients with severe IBD.