Diabetes and the Small Intestine

Diabetes mellitus (DM) and its associated complications are becoming increasingly prevalent. Gastrointestinal symptoms associated with diabetes is known as diabetic enteropathy (DE) and may manifest as either diarrhea, fecal incontinence, constipation, dyspepsia, nausea, and vomiting or a combination of symptoms. The long-held belief that vagal autonomic neuropathy is the primary cause of DE has recently been challenged by newer theories of disease development. Specifically, hyperglycemia and the resulting oxidative stress on neural networks, including the nitrergic neurons and interstitial cells of Cajal (ICC), are now believed to play a central role in the development of DE. DE occurs in the majority of patients with diabetes; however, tools for early diagnosis and targeted therapy to counter the detrimental and potentially irreversible effects on the small bowel are lacking. Delay in diagnosis is further compounded by the fact that DE symptoms overlap with those of gastroparesis or can be confused with side effects from diabetes medications. Still, early recognition of the presence of DE is essential to mitigating symptoms and preventing further progression of complications including dysmotility and malabsorption. Current diagnostic modalities include manometry, wireless motility capsule (SmartPill™), and scintigraphy; however, these are not regularly utilized in clinical practice due to limited availability. Several medications are available for symptom relief in DE patients including rifaximin for small intestinal bacterial overgrowth (SIBO) and somatostatin analogues for diarrhea. While rodent models on stem cell therapy and alteration of the microbiome are promising, there is still a great need for further research on the pathologic underpinnings and development of novel treatment modalities for DE.