Rationale: The systemic consequences of hypoglycemic brain injury beyond the central nervous system remain poorly understood. While the brain-gut axis is a pivotal communication network, clinical evidence linking hypoglycemia to gut dysmotility is confounded by comorbidities like autonomic neuropathy. This case report aims to present the first documented evidence of isolated hypoglycemic brain injury inducing transient, profound diarrhea through a hypothesized brain-gut pathway, in a patient with all confounding factors rigorously excluded and premorbid normal gut histology. Patient concerns: A 65-year-old male with type 2 diabetes suffered an insulin overdose, resulting in profound hypoglycemia (glucose 1.8 mmol/L) and a 10-minute comatose state. Twenty-four hours post-hypoglycemia, he developed acute-onset, large-volume watery diarrhea (3–4 episodes daily). Diagnoses: A comprehensive diagnostic workup excluded all common infectious, inflammatory, autoimmune, metabolic, and structural causes. Interventions: The diarrhea proved refractory to a sequential therapeutic regimen including loperamide, smectite, Saccharomyces boulardii, and cholestyramine. Outcomes: The symptoms persisted unabated until their abrupt and complete resolution on day 11, without therapeutic intervention. At 3-month follow-up, the patient remained asymptomatic with normal bowel function and objective tests. Lessons: This case illuminates a novel, self-limiting cerebro-enteral pathway activated by hypoglycemia, which we hypothesize is mediated by blood–brain barrier-disruption and corticotropin-releasing hormone-driven neurohumoral cascades. It underscores the need to consider central nervous system injury in the differential diagnosis of unexplained acute diarrhea and highlights the necessity for monitoring gastrointestinal symptoms post-hypoglycemia.
Liu et al. (2026) studied this question.