title: Diabetic autonomic neuropathy affects symptom generation and brain-gut axis.
abstract: OBJECTIVE
  Long-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.
  
  
  METHODS
  Fifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.
  
  
  RESULTS
  Diabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2-P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001).
  
  
  CONCLUSIONS
  This study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.
authors.affiliation: Corresponding author: Christina Brock, cb@mech-sense.com.
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.forename: Eirik
authors.initials: E
authors.lastname: Søfteland
authors.forename: Veronica
authors.initials: V
authors.lastname: Gunterberg
authors.forename: Jens Brøndum
authors.initials: JB
authors.lastname: Frøkjær
authors.forename: Dina
authors.initials: D
authors.lastname: Lelic
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
authors.forename: Georg
authors.initials: G
authors.lastname: Dimcevski
authors.forename: Hans
authors.initials: H
authors.lastname: Gregersen
authors.forename: Magnus
authors.initials: M
authors.lastname: Simrén
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000503:physiopathology; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology*; D041981:Gastrointestinal Tract / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life
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