BACKGROUND: Patients hospitalized with moderately severe or acute severe ulcerative colitis (UC) may experience metabolic disturbances, including alterations in insulin resistance due to inflammation and the administration of glucocorticoids (GCs). This pilot study aimed to evaluate insulin sensitivity in patients hospitalized for moderately severe to severe UC. METHOD: Patients hospitalized for moderately-severely active UC at Örebro University Hospital, Sweden, were eligible for inclusion. Quantification of insulin sensitivity was performed using the hyperinsulinemic euglycemic clamp (HEC) methodology. Assessment of insulin sensitivity was performed during both the index flare and while patients were in steroid-free clinical, biochemical and endoscopic remission during follow-up. Additionally, healthy controls were evaluated using HEC for comparison. RESULTS: Five patients with moderately-severely active UC, treated with intravenous GCs for ≥2 days, were included and underwent HEC assessment. During the index flare, four patients received second-line treatment with infliximab due to non-response to GC, and one patient was subsequently referred for acute subtotal colectomy. At inclusion, all five patients exhibited significantly reduced insulin sensitivity, and levels appeared similar regardless of the outcome of the index flare. At remission during follow-up, the insulin sensitivity was restored to levels comparable to healthy controls ( CONCLUSION: The study demonstrates that patients with moderately severe to severe UC experience significant insulin resistance, irrespective of the outcome of the flare. The reduced insulin sensitivity is likely driven by a combination of active inflammation and GC treatment, as insulin sensitivity returned to normal levels when patients achieved remission during follow-up.