How is the autonomic nerve function different between gastroesophageal reflux disease alone and gastroesophageal reflux disease with diabetes mellitus neuropathy?

TO THE EDITOR: I read with great interest the paper entitled "Gastroesophageal reflux disease in type II diabetes mellitus with or without peripheral neuropathy" by Lee et al,1 which was published in July 2011 issue of Journal of Neurogastroenterology and Motility. The authors investigated gastroesophageal reflux disease (GERD) among patients with type II diabetes mellitus, and showed interesting results as follows. Erosive esophagitis (EE) was more frequent (66.7%) in diabetes mellitus (DM) patients with neuropathy than those without neuropathy 33.3%; asymptomatic EE was significantly more frequent (21.1%) in DM group with neuropathy than in those without neuropathy (5.3%).1 According to the multivariate analysis, peripheral neuropathy was the only significantly associated factor with an adjusted OR of 5.01 (P = 0.013).

This study reminds us that EE patients may be asymptomatic, and some patients with EE may be misdiagnosed. Therefore, we need to pay attention to those special population, such as, DM patient with neuropathy as well as those with high risk of EE. Esophagogastroduodenoscopy is helpful for diagnosis.

Clinically, we are fully aware of ruling out organic lesion before the diagnosis of GERD, such as, pyloric obstruction. We may ignore diseases with no evidence for structural abnormalities, such as gastrointestinal motility disorders of either neuropathy or myopathy, which are at high risk to develop GERD by delayed gastric emptying, impaired esophago-gastric junction, esophageal clearance and so on.

I agree Dr. Lee's1 opinion that the greater incidence of transient lower esophageal sphincter relaxation (TLESR) that is responsible for the GERD is related to diabetic autonomic neuropathy. Autonomic neuropathy in DM may result in delayed gastric emptying, which induces gastric dilation associated with TLESR.

Pathogenesis of GERD is complicated and not well understood yet. It is well known that if anti-reflux therapy is discontinued, symptoms often reoccur. Even severe EE was healed after proton pump inhibitor therapy, but esophageal dysmotility was not improved.2 Studies have confirmed that autonomic nerve function in GERD was abnormal,3,4 and proton pump inhibitor could remarkably reduce reflux symptoms and improve quality of life, however, autonomic nerve function was failed to be normalized,5 suggesting that abnormal autonomic nerve function is one of pathogenesis in GERD.

It could be assumed that GERD may be based on both GERD related abnormal autonomic nerve function and DM neuropathy. Autonomic nerve function in EE without DM may be different from those EE with DM neuropathy. What difference underlies in the autonomic nerve function between GERD alone and GERD with DM neuropathy? I suppose those GERD patients with developing DM neuropathy may have different clinical feature from DM neuropathy with developing EE, or GERD alone.