LAUSR

Type I diabetes mellitus (DM) affects 0.5% of the US population, with type II DM affecting 8.5% [1]. There are a multitude of complications attributed to DM including gastrointestinal dysfunction [2] with up to 75% of patients experiencing gastrointestinal symptoms, usually in the setting of autonomic neuropathy [3, 4]. Females with DM have an overall increased likelihood of experiencing gastrointestinal symptoms as compared with males [5, 6]. Gastrointestinal symptoms often, but not invariably, correlate with glycemic control as well as the duration of DM [6]. Chronic watery diarrhea, among the most debilitating gastrointestinal symptom due to DM, is termed diabetic diarrhea (DD). The pathophysiology of DD is complex. Although hyperglycemia-induced neuropathy of the enteric nervous system is a likely cause, other causes include loss of the interstitial cells of Cajal (ICC) and enteric glial cells (ECG), oxidative stress, and inflammation, pathologies that all impair regenerative processes and affect signaling. Altered gut motility and aberrant intestinal absorption are downstream effects. Epithelial cell damage and alterations of colonic stem cells have been implicated as well. Since the differential diagnosis of DD is broad, it is ultimately a diagnosis of exclusion. Evaluation should be aimed at excluding medication and dietary causes in addition to organic pathologies of the pancreas, small bowel, colon, and endocrine system. Small intestinal bacterial overgrowth (SIBO) is often included in the differential. Like many DMrelated diseases, glycemic control is the principal treatment. Symptomatic support is achieved with several medications including loperamide, diphenoxylate, bile acid sequestrants, and selective 5-HT3 antagonists. Clonidine and octreotide are infrequently used. Well-tolerated, gut-specific anti-diarrheal medications like eluxadoline should be investigated as potential therapies. This review will highlight the pathophysiology, clinical presentation, differential diagnoses, current, and future therapies of DD.