Diabetic gastrointestinal motility disorders and the role of enteric nervous system: Current status and future directions

Abstract

Gastrointestinal manifestations of diabetes are common and a source of significant discomfort and disability. Diabetes affects almost every part of gastrointestinal tract from the esophagus to the rectum and causes a variety of symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and constipation. Understanding the underlying mechanisms of diabetic gastroenteropathy is important to guide development of therapies for this common problem. Over recent years, the data regarding the pathophysiology of diabetic gastroenteropathy is expanding. In addition to autonomic neuropathy causing gastrointestinal disturbances the role of enteric nervous system is becoming more evident. In this review, we summarize the reported alterations in enteric nervous system including enteric neurons, interstitial cells of Cajal and neurotransmission in diabetic animal models and patients. We also review the possible underlying mechanisms of these alterations, with focus on oxidative stress, growth factors and diabetes induced changes in gastrointestinal smooth muscle. Finally, we will discuss recent advances and potential areas for future research related to diabetes and the ENS such as gut microbiota, micro-RNAs and changes in the microvasculature and endothelial dysfunction.

Dysfunction of the lower gastrointestinal tract as a complication of diabetes — a problematic issue in the diabetic care

“…Among metabolic disorders, apart from the obvious role of hyperglycemia in development of neuropathy, disorders of lipid metabolism are also highlighted [1,7,8,15]. These disorders are a subject of a number of research conducted in recent years, e.g.…”

“…Due to the fact that autonomic neuropathy in diabetes in respect to other systems is well-known, gastrointestinal disorders have also been linked primarily to it. However, available results of research concerning the relation between symptoms of AN in respect to other systems and symptoms concerning the gastrointestinal tract are controversial [1].…”

“…However, free fatty acids, hypertriglyceridemia and reduced HDL cholesterol concentration may intermediate in oxidative and inflammatory processes damaging tissues and, according to some researchers, correlate with development of neuropathy [7]. Researchers have shown, on the basis of animal models, that a diet rich in lipids may lead to loss of enteric neurons [1].…”

“…Subclinical diabetic autonomic neuropathy can occur within a year of diagnosis of type 2 diabetes and two years of diagnosis of type 1 diabetes, while first symptoms appear only after many years [7,8]. Taking recent findings into consideration, it is known that not only autonomic neuropathy alone is responsible for these complications; complex mechanisms underlying damage to the enteric nervous system, damage to the interstitial cells of Cajal, or damage to the smooth muscles are increasingly being cited as significant in etiopathogenesis of diabetic gastroenteropathy [1,4].…”

“…It is thought that beyond commonly diagnosed autonomic neuropathy (AN), other mechanisms influence their occurrence [1]. Diabetic neuropathy significantly decreases patients' quality of life.…”