Diabetic Enteropathy: From Molecule to Mechanism-Based Treatment

Abstract

The incidence of the micro- and macrovascular complications of diabetes is rising, mirroring the increase in the worldwide prevalence. Arguably, the most common microvascular complication is neuropathy, leading to deleterious changes in both the structure and function of neurons. Amongst the various neuropathies with the highest symptom burden are those associated with alterations in the enteric nervous system, referred to as diabetic enteropathy. The primary aim of this review is to provide a contemporaneous summary of pathophysiology of diabetic enteropathy thereby allowing a “molecule to mechanism” approach to treatment, which will include 4 distinct aspects. Firstly, the aim is to provide an overview of the diabetes-induced structural remodelling, biochemical dysfunction, immune-mediated alterations, and inflammatory properties of the enteric nervous system and associated structures. Secondly, the aim is to provide a synopsis of the clinical relevance of diabetic enteropathy. Thirdly, the aim is to discuss the various patient-reported outcome measures and the objective modalities for evaluating dysmotility, and finally, the aim is to outline the clinical management and different treatment options that are available. Given the burden of disease that diabetic enteropathy causes, earlier recognition is needed allowing prompt investigation and intervention, which may lead to improvements in quality of life for sufferers.

Domination of Gastric Complications Among Diabetic Patients

“…Traditional therapy for delayed gastric emptying has focused on supportive treatment, and there is no significant effective therapy. Low-energy shock wave can increase gastric contraction and emptying by activating axonal regeneration and increasing myenteric plexus, but not related with motility peptides [3,[36][37][38] . Gastric electrical stimulation (GES) (Enterra, Medtronics, Inc.) was approved by FDA in 2000 as a Humanitarian Use Device for patients with refractory diabetic or idiopathic GP [39][40][41] .…”

Diabetic autonomic neuropathy of the gastrointestinal tract

“…Thus, the digestive system, being under the control of the central nervous system, has considerable independence in regulating its motility. It seems that the amount of information sent to the CNS is much larger than that received; for example, in parasympathetic nerves, about 80% of nerve fibres are afferent [6].…”

“…polyol, hexosamine, methylglycine, diacylglycerol resynthesis). By attaching themselves to proteins or fats, the resulting molecules cause the formation of so-called advanced glycation end-products (AGEs) [6]. They cause damage to the structure of nerve cells and interfere with their function.…”

Serum levels of intestinal alkaline phosphatase in type 2 diabetic patients with enteropathy

“…3 Amongst the diabetic complications with the highest symptom burden, yet frequently underrecognized and suboptimally treated, are those associated with alterations in the enteric nervous system, referred to as diabetic enteropathy. 4 In spite of other problems, the major disabling complaints present in patients are intestinal disorders like constipation and diarrhea. 5 Small intestinal and colorectal dysfunctions are common in patients with longstanding diabetes, especially in those with gastroparesis.…”

“…IAP has significant roles in our gastrointestinal system, for example, it is vital for regulation of lipid absorption, which may be important in diabetic patients. 4,10 But even after extensive search, there was dearth of literature related to IAP levels in serum of diabetic enteropathy subjects. So, using a case-control design we recruited T2DM subjects and determined the levels of IAP in the serum of these participants.…”