Gastrointestinal Motility Among Diabetes Patients

Summary

Gastrointestinal (GI) symptoms including vomiting, nausea, abdominal pain, constipation or chronic diarrhea affect a large number of patients with diabetes mellitus (DM). Furthermore, abnormal GI transit times restrict correct dosing of medication. Two new methods, in combination only available at Aarhus University Hospital (AUH), allow examination of human whole-gut function with a high degree of detail: PET-scans (positron emission tomography scans) of cholinergic signaling in the bowel wall The most important nerve fibers stimulating GI peristalsis use acetylcholine as neurotransmitter. The novel PET technique, \[11C\] Donepezil PET/CT (Donepezil PET/CT scan based on a carbon isotope), developed at AUH, allows in vivo quantification of cholinergic cells within the bowel wall. 3D-Transit With 3D-Transit electromagnetic capsules are followed during their passage through the GI tract. The novel method provides highly detailed information about regional and whole-gut passage times and contractility patterns. Study protocol 20 healthy subjects and 25 diabetic patients with severe GI symptoms will be included. 1. With \[11C\]donepezil PET/CT, we aim to describe the degree of cholinergic denervation of the intestine in DM patients with GI severe symptoms. 2. Using 3D-Transit in DM patients before and during intervention with acetyl cholinesterase inhibitor we aim to determine how cholinergic denervation of the intestine contributes to abnormal GI transit patterns. 3. Comparing the transit times of DM patients with either vomiting or diarrhea as main symptoms, we aim to provide pilot data on phenotypes of diabetic GI dysfunction. 4. We aim to explore various aspects of "pan-enteric" dysfunction in DM, including prolonged gastric emptying secondary to severe constipation and delayed small intestinal transit in patients with symptoms of gastroparesis with or without delayed gastric emptying Perspectives Detailed information about cholinergic denervation in DM and objective classification of the pathophysiology of diabetic GI dysfunction may allow targeted future treatment of individual patients.

Timeline

Start

2015-10

Primary completion

2019-02-11

Completion

2019-02-11

Publications

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• Background Bytzer P, Talley NJ, Leemon M, Young LJ, Jones MP, Horowitz M. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med. 2001 Sep 10;161(16):1989-96. doi: 10.1001/archinte.161.16.1989.
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• Background Vanormelingen C, Tack J, Andrews CN. Diabetic gastroparesis. Br Med Bull. 2013;105:213-30. doi: 10.1093/bmb/ldt003. Epub 2013 Jan 29.
• Background Jones KL, Russo A, Stevens JE, Wishart JM, Berry MK, Horowitz M. Predictors of delayed gastric emptying in diabetes. Diabetes Care. 2001 Jul;24(7):1264-9. doi: 10.2337/diacare.24.7.1264.
• Background Sarosiek I, Selover KH, Katz LA, Semler JR, Wilding GE, Lackner JM, Sitrin MD, Kuo B, Chey WD, Hasler WL, Koch KL, Parkman HP, Sarosiek J, McCallum RW. The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology. Aliment Pharmacol Ther. 2010 Jan 15;31(2):313-22. doi: 10.1111/j.1365-2036.2009.04162.x. Epub 2009 Oct 8.
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• Background Olausson EA, Brock C, Drewes AM, Grundin H, Isaksson M, Stotzer P, Abrahamsson H, Attvall S, Simren M. Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms. Neurogastroenterol Motil. 2013 Mar;25(3):e224-32. doi: 10.1111/nmo.12075. Epub 2013 Jan 15.
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• Background Guy RJ, Dawson JL, Garrett JR, Laws JW, Thomas PK, Sharma AK, Watkins PJ. Diabetic gastroparesis from autonomic neuropathy: surgical considerations and changes in vagus nerve morphology. J Neurol Neurosurg Psychiatry. 1984 Jul;47(7):686-91. doi: 10.1136/jnnp.47.7.686.
• Background Guo C, Quobatari A, Shangguan Y, Hong S, Wiley JW. Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat. Neurogastroenterol Motil. 2004 Jun;16(3):335-45. doi: 10.1111/j.1365-2982.2004.00524.x.
• Background Tay SS, Wong WC. Short- and long-term effects of streptozotocin-induced diabetes on the dorsal motor nucleus of the vagus nerve in the rat. Acta Anat (Basel). 1994;150(4):274-81. doi: 10.1159/000147630.
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• Background Horvath VJ, Vittal H, Lorincz A, Chen H, Almeida-Porada G, Redelman D, Ordog T. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis. Gastroenterology. 2006 Mar;130(3):759-70. doi: 10.1053/j.gastro.2005.12.027.
• Background Punkkinen J, Farkkila M, Matzke S, Korppi-Tommola T, Sane T, Piirila P, Koskenpato J. Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy. Diabet Med. 2008 May;25(5):570-7. doi: 10.1111/j.1464-5491.2008.02428.x.
• Background Hopkins DA, Bieger D, deVente J, Steinbusch WM. Vagal efferent projections: viscerotopy, neurochemistry and effects of vagotomy. Prog Brain Res. 1996;107:79-96. doi: 10.1016/s0079-6123(08)61859-2. No abstract available.
• Background Haase AM, Gregersen T, Schlageter V, Scott MS, Demierre M, Kucera P, Dahlerup JF, Krogh K. Pilot study trialling a new ambulatory method for the clinical assessment of regional gastrointestinal transit using multiple electromagnetic capsules. Neurogastroenterol Motil. 2014 Dec;26(12):1783-91. doi: 10.1111/nmo.12461. Epub 2014 Oct 27.
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