Brain changes in diabetes mellitus patients with gastrointestinal symptoms

Table 2 Findings with quantitative sensory testing and evoked brain potentials in patients with diabetes and gastrointestinal symptoms

Ref.	Method	Results
Frøkjær et al[11]	12 healthy controls and 12 type-1 diabetes patients with proven autonomic neuropathy and severe GI symptoms had their sensitivity to stimulations in the oesophagus and duodenum assessed	A 46% increase in the somatic referred pain areas, indicating central hyper excitability. The results also indicated that the sensory nerves in the GI tract were widely affected. Furthermore it is suggested that future targets in the treatment of GI symptoms in DM patients could be based on modulation of the central nervous system excitability
Frøkjær et al[63]	14 type-1 diabetes patients with autonomic neuropathy and GI symptoms and 15 healthy volunteers had their sensitivity to electrical oesophageal and median nerve stimulations assessed by using an euglycemic-hyperinsulinemic clamp. The EPs were also collected	GI symptoms correlated with characteristics of brain potentials in the DM patients. These results indicate a change in peripheral visceral nerves as well as in the central nervous system
Frøkjær et al[47]	Evoked potentials to oesophageal and median nerve stimulations were recorded in 14 type-1 diabetes patients with GI symptoms	The study concluded that acute hyperglycaemia had no effect on the brain activation of visceral and somatic stimulations
Frøkjær et al[62]	15 healthy volunteers and 14 type-1-diabetes patients with autonomic neuropathy and related GI symptoms had their EPs recorded following painful oesophageal electrical stimulation	Evidence of altered central processing to visceral stimulation in diabetes was found. Compared to controls, the patients with diabetes had a posterior shift of the electrical sources in the anterior cingulate cortex, and additional sources close to the posterior insula and in medial frontal gyrus
Frøkjær et al[45]	Ultrasound monitored oesophageal distension was used to study 17 patients with longstanding DM and GI symptoms and 13 healthy controls	The reduced sensitivity was associated with the presence of peripheral neuropathy. This indicates a coexisting change within the visceral and somatic neuropathy
Brock et al[64]	14 type-1 diabetes patients with diabetes autonomy neuropathy and 15 healthy volunteers underwent multichannel EEG during painful electrical stimulation of the lower esophagus	Central neuroplastic changes within DM patients were found in the insular region, and it was suggested that the GI symptoms are due to the abnormal insular processing
Lelic et al[46]	Electrical stimulation of the rectum was done in 12 healthy controls and 12 type 1 diabetes patients with GI symptoms while having their EPs recorded	Changes in the cingulate-operculum brain network were found in DM patients with GI symptoms. Changes could serve as a biomarker of disturbed sensory visceral processing and GI symptoms in patients with diabetes
Brock et al[4]	15 healthy volunteers and 15 diabetes patients with GI symptoms and clinical suspicion of autonomic neuropathy were included. Electrical source analysis to painful recto-sigmoid electrostimulations was modelled	Patients with autonomic neuropathy and GI symptoms had evidence for altered brain activation and dysregulation of the central regulation of the autonomic nervous system, which could explain appearance and persistence of upper GI symptoms
Søfteland et al[48]	16 healthy controls and 20 DM patients with sensorimotor polyneuropathy had their heart rate variability and peripheral tactile thresholds recorded and underwent a cold-pressor-test	The patients in this study suffered from generalized polyneuropathy evident as autonomic neuropathy, peripheral hypoesthesia and central changes manifested as impaired conditioned pain modulation
Lelic et al[61]	EPs to electrical esophageal stimulation were achieved in 23 diabetes patients with upper GI symtoms and 27 healthy controls. Network analysis between active sources were performed	There was a reorganisation in the opercular cortex, which was correlated with GI symptoms. It was proposing that the changes in the operculo-cingulate cortex could help explain the development and maintenance of GI symptoms in diabetes patients

EPs: Evoked brain potentials; GI: Gastrointestinal; EEG: Electroencephalography; DM: Diabetes mellitus.