title: Peripheral and central nervous contribution to gastrointestinal symptoms in diabetic patients with autonomic neuropathy.
abstract: OBJECTIVE
  Long-term diabetes mellitus (DM) has been associated with neuronal changes in the enteric, peripheral and/or central nervous system. Moreover, abnormal visceral sensation and gastrointestinal (GI) symptoms are seen in up to 75% of patients. To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling.
  
  
  METHODS
  Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis (besa).
  
  
  RESULTS
  Diabetic patients had higher stimulus intensities to evoke painful sensation (p ≤ 0.001), longer latencies of N2 and P2 components (both p ≤ 0.001), and lower amplitudes of P1-N2 and N2-P2 complexes (p ≤ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03).
  
  
  CONCLUSIONS
  DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN. This enhanced understanding of DAN may have future clinical and therapeutical implications.
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. cb@mech-sense.com
authors.forename: C
authors.initials: C
authors.lastname: Brock
authors.forename: C
authors.initials: C
authors.lastname: Graversen
authors.forename: J B
authors.initials: JB
authors.lastname: Frøkjaer
authors.forename: E
authors.initials: E
authors.lastname: Søfteland
authors.forename: M
authors.initials: M
authors.lastname: Valeriani
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement