title: Brain changes in diabetes mellitus patients with gastrointestinal symptoms.
abstract: Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system (CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal (GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testing mainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes, especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Eirik
authors.initials: E
authors.lastname: Søfteland
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Georg
authors.initials: G
authors.lastname: Dimcevski
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Farmer
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Christina
authors.initials: C
authors.lastname: Brock
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Jens B
authors.initials: JB
authors.lastname: Frøkjær
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Klaus
authors.initials: K
authors.lastname: Krogh
authors.affiliation: Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
keywords: Brain; Diabetes mellitus; Electroencephalogram; Gastrointestinal; Magnetic resonance imaging
references.citation: Brain Res Bull. 1999 Jun;49(3):155-62
references.pmid: 10435778
references.citation: Diabet Med. 1999 Aug;16(8):670-4
references.pmid: 10477212
references.citation: Scand J Gastroenterol. 2000 Feb;35(2):152-9
references.pmid: 10720112
references.citation: Scand J Gastroenterol. 2001 Aug;36(8):827-32
references.pmid: 11495078
references.citation: Arch Intern Med. 2001 Sep 10;161(16):1989-96
references.pmid: 11525701
references.citation: Diabetologia. 2001 Nov;44(11):1973-88
references.pmid: 11719828
references.citation: Am J Physiol Gastrointest Liver Physiol. 2002 Jul;283(1):G95-103
references.pmid: 12065296
references.citation: Eur J Pharmacol. 2004 Apr 19;490(1-3):159-68
references.pmid: 15094082
references.citation: Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E199-206
references.pmid: 15271645
references.citation: J Neurosci. 2004 Nov 17;24(46):10410-5
references.pmid: 15548656
references.citation: Gut. 2006 Jul;55(7):926-32
references.pmid: 16091554
references.citation: Diabetes. 2005 Dec;54(12):3435-41
references.pmid: 16306359
references.citation: Diabetes Care. 2006 Nov;29(11):2539-48
references.pmid: 17065699
references.citation: Diabetes Care. 2007 May;30(5):1193-9
references.pmid: 17290035
references.citation: Scand J Gastroenterol. 2007 Apr;42(4):432-40
references.pmid: 17454852
references.citation: Diabetologia. 2007 Jul;50(7):1509-16
references.pmid: 17492428
references.citation: Pain. 2007 Oct;131(3):320-9
references.pmid: 17521809
references.citation: Pancreas. 2007 Jul;35(1):22-9
references.pmid: 17575541
references.citation: Nat Rev Neurosci. 2008 Jan;9(1):36-45
references.pmid: 18094705
references.citation: Diabet Med. 1991 Feb-Mar;8(2):162-7
references.pmid: 1827403
references.citation: Med Sci Monit. 2008 Apr;14(4):CR213-20
references.pmid: 18376350
references.citation: Scand J Gastroenterol. 2008;43(9):1066-75
references.pmid: 18609155
references.citation: Pharmacol Ther. 2008 Oct;120(1):1-34
references.pmid: 18616962
references.citation: Diabetes. 2008 Nov;57(11):3083-9
references.pmid: 18694971
references.citation: Diab Vasc Dis Res. 2008 Nov;5(4):336-44
references.pmid: 18958844
references.citation: Diabetes Care. 2009 Mar;32(3):445-50
references.pmid: 19151204
references.citation: Diabetes Care. 2009 Jul;32(7):1274-7
references.pmid: 19366960
references.citation: J Clin Neurophysiol. 2009 Aug;26(4):227-35
references.pmid: 19584750
references.citation: Jpn J Radiol. 2010 May;28(4):266-72
references.pmid: 20512543
references.citation: Eur J Clin Invest. 2010 Oct;40(10):883-6
references.pmid: 20624170
references.citation: Eur J Pain. 2011 Mar;15(3):249-57
references.pmid: 20813568
references.citation: Neurology. 2010 Sep 14;75(11):997-1002
references.pmid: 20837967
references.citation: Diabetes Care. 2010 Oct;33(10):2285-93
references.pmid: 20876709
references.citation: Curr Med Res Opin. 2011 Mar;27(3):547-58
references.pmid: 21222567
references.citation: Diabetes Res. 1990 Sep;15(1):15-9
references.pmid: 2132195
references.citation: Exp Clin Endocrinol Diabetes. 2011 May;119(5):265-70
references.pmid: 21472662
references.citation: Clin Neurophysiol. 2011 Oct;122(10):1943-50
references.pmid: 21474371
references.citation: Curr Diab Rep. 2011 Aug;11(4):310-22
references.pmid: 21667355
references.citation: Expert Opin Ther Targets. 2011 Oct;15(10):1153-62
references.pmid: 21749267
references.citation: Curr Diabetes Rev. 2012 May;8(3):229-36
references.pmid: 22283678
references.citation: Eur J Pain. 2012 Sep;16(8):1128-36
references.pmid: 22407963
references.citation: Neurobiol Dis. 2013 Mar;51:56-65
references.pmid: 22446165
references.citation: Cochrane Database Syst Rev. 2012 Jun 13;(6):CD007543
references.pmid: 22696371
references.citation: Pharmacol Rev. 2012 Jul;64(3):722-79
references.pmid: 22722894
references.citation: Neurogastroenterol Motil. 2012 Nov;24(11):1016-e544
references.pmid: 22738347
references.citation: Diabetes Care. 2013 Mar;36(3):662-8
references.pmid: 23139372
references.citation: Mol Med Rep. 2013 Feb;7(2):431-40
references.pmid: 23232924
references.citation: Eur J Pain. 2013 Jul;17(6):820-31
references.pmid: 23239083
references.citation: Neurogastroenterol Motil. 2013 Mar;25(3):e224-32
references.pmid: 23316944
references.citation: Neuroscience. 2013 May 1;237:96-105
references.pmid: 23384609
references.citation: Diabetes. 2013 Mar;62(3):696-7
references.pmid: 23431013
references.citation: Oxid Med Cell Longev. 2013;2013:168039
references.pmid: 23738033
references.citation: Exp Clin Endocrinol Diabetes. 2013 Jun;121(6):354-60
references.pmid: 23757052
references.citation: Eur J Pharmacol. 2013 Nov 5;719(1-3):180-6
references.pmid: 23872412
references.citation: Diabetes Care. 2013 Dec;36(12):4036-42
references.pmid: 23939539
references.citation: Rep Prog Phys. 2013 Sep;76(9):096601
references.pmid: 24006360
references.citation: Diabetes Care. 2013 Nov;36(11):3698-705
references.pmid: 24026548
references.citation: Neurogastroenterol Motil. 2014 Jan;26(1):46-58
references.pmid: 24050116
references.citation: World J Gastroenterol. 2013 Nov 14;19(42):7282-91
references.pmid: 24259959
references.citation: J Diabetes Complications. 2014 May-Jun;28(3):370-7
references.pmid: 24355661
references.citation: Brain Nerve. 2014 Feb;66(2):135-47
references.pmid: 24523312
references.citation: PLoS One. 2014 Feb 20;9(2):e89229
references.pmid: 24586614
references.citation: Neurology. 2014 Apr 1;82(13):1132-41
references.pmid: 24647028
references.citation: Neurogastroenterol Motil. 2014 Jun;26(6):862-73
references.pmid: 24750321
references.citation: Diabetes Technol Ther. 2014 Oct;16(10):688-94
references.pmid: 24892361
references.citation: Pediatr Blood Cancer. 2014 Oct;61(10):1724-8
references.pmid: 24920351
references.citation: Diabetes. 2014 Jul;63(7):2244-52
references.pmid: 24931032
references.citation: Diabetes. 2014 Jul;63(7):2232-43
references.pmid: 24931034
references.citation: ScientificWorldJournal. 2014;2014:523216
references.pmid: 25254248
references.citation: Compr Physiol. 2014 Oct;4(4):1339-68
references.pmid: 25428846
references.citation: Endocrinology. 1988 Oct;123(4):2009-13
references.pmid: 2901341
references.citation: Scand J Pain. 2017 Dec 29;2(3):95-104
references.pmid: 29913746
references.citation: Arch Pathol Lab Med. 1982 May;106(5):214-7
references.pmid: 6896132
references.citation: AJNR Am J Neuroradiol. 1995 Feb;16(2):241-51
references.pmid: 7726068
references.citation: J Neurol Neurosurg Psychiatry. 1994 Nov;57(11):1360-5
references.pmid: 7964812
references.citation: Paraplegia. 1994 Aug;32(8):565-9
references.pmid: 7970862
references.citation: N Engl J Med. 1993 Sep 30;329(14):977-86
references.pmid: 8366922
references.citation: Metabolism. 1996 Dec;45(12):1508-13
references.pmid: 8969284
references.citation: Diabetes Care. 1997 Jun;20(6):1013-8
references.pmid: 9167117
references.citation: Diabetes. 1997 Nov;46(11):1840-5
references.pmid: 9356034