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Kufaishi H, Mizrak HI, Brock B, Hansen TW, Rossing P, Hansen CS. Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study. J Diabetes Complications 2024; 38:108745. [PMID: 38615421 DOI: 10.1016/j.jdiacomp.2024.108745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 04/09/2024] [Accepted: 04/10/2024] [Indexed: 04/16/2024]
Abstract
OBJECTIVE We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.
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Affiliation(s)
| | | | - Birgitte Brock
- Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Meling S, Tjora E, Eichele H, Nedergaard RB, Ejskjaer N, Brock C, Søfteland E. The PanGut-study: Evoked potentials following rectal balloon distention, a way of evaluating diabetic autonomic neuropathy in the gut? J Diabetes Complications 2023; 37:108452. [PMID: 36965366 DOI: 10.1016/j.jdiacomp.2023.108452] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/26/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023]
Abstract
AIM There is a lack of methods for investigating the autonomic nerves of the gastrointestinal tract. Our aim was to explore a novel test measuring visceral sensory evoked potentials (EPs) in response to rapid balloon distention in the rectum and compare it to established tests for diabetic neuropathy. METHOD Participants with longstanding type 2 diabetes, newly onset, untreated diabetes <1 year, and matched controls, were included. Tests included cardiovascular reflex tests, orthostatic blood pressure, electrical skin conductance assessment, sural nerve testing and monofilament test. The rectal balloon distention pressure at earliest sensation and threshold of unpleasantness were identified and used to elicit mechanical EPs. RESULTS The pressure at earliest sensation was higher in people with diabetes, 0.038 (0.012) bar vs. controls 0.030 (0.009) bar, p = 0.002, and in people with signs of peripheral neuropathy, 0.045 (0.014) bar, p < 0.01. Clinical correlations between EP amplitude and latency, and other tests were found. CONCLUSIONS Rectal hyposensitivity was associated with both longstanding and early diabetes, indicating enteric sensory dysfunction already in early stages of diabetes. Correlation analyses may indicate that central afferent processing is affected in parallel with peripheral neuronal function.
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Affiliation(s)
- Sondre Meling
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
| | - Erling Tjora
- Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway
| | - Heike Eichele
- Department of Biological and Medical Psychology, Faculty of Psychology, University of Bergen, Bergen, Norway; Regional Resource Centre for Autism, ADHD and Tourette Syndrome Western Norway, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway
| | - Rasmus Bach Nedergaard
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Niels Ejskjaer
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Jutland and Department of Endocrinology, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Steno Diabetes Center North Jutland and Department of Endocrinology, Aalborg, Denmark
| | - Eirik Søfteland
- Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Røikjer J, Croosu SS, Hansen TM, Frøkjær JB, Brock C, Mørch CD, Ejskjaer N. The co-existence of sensory and autonomic neuropathy in type 1 diabetes with and without pain. Acta Diabetol 2023; 60:777-785. [PMID: 36881186 DOI: 10.1007/s00592-023-02062-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 02/21/2023] [Indexed: 03/08/2023]
Abstract
AIMS To investigate the co-existence of diabetic peripheral neuropathy (DPN), painful diabetic peripheral neuropathy (PDPN), and cardiac autonomic neuropathy (CAN) and to establish a model to predict CAN based on peripheral measurements. METHODS Eighty participants (20 type 1 diabetes (T1DM) + PDPN, 20 T1DM + DPN, 20 T1DM-DPN (without DPN), and 20 healthy controls (HC)) underwent quantitative sensory testing, cardiac autonomic reflex tests (CARTs), and conventional nerve conduction. CAN was defined as ≥ 2 abnormal CARTs. After the initial analysis, the participants with diabetes were re-grouped based on the presence or absence of small (SFN) and large fibre neuropathy (LFN), respectively. A prediction model for CAN was made using logistic regression with backward elimination. RESULTS CAN was most prevalent in T1DM + PDPN (50%), followed by T1DM + DPN (25%) and T1DM-DPN and HC (0%). The differences in prevalence of CAN between T1DM + PDPN and T1DM-DPN/HC were significant (p < 0.001). When re-grouping, 58% had CAN in the SFN group and 55% in the LFN group, while no participants without either SFN or LFN had CAN. The prediction model had a sensitivity of 64%, a specificity of 67%, a positive predictive value of 30%, and a negative predictive value of 90%. CONCLUSION This study suggests that CAN predominantly co-exists with concomitant DPN.
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Affiliation(s)
- Johan Røikjer
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Hobrovej 18-22. 9000, Aalborg, Denmark.
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
| | - Suganthiya Santhiapillai Croosu
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Hobrovej 18-22. 9000, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Tine Maria Hansen
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Jens Brøndum Frøkjær
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Christina Brock
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Hobrovej 18-22. 9000, Aalborg, Denmark
- Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark
- Mech-Sense, Aalborg University Hospital, Aalborg, Denmark
- Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Carsten Dahl Mørch
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg, Denmark
- Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Hobrovej 18-22. 9000, Aalborg, Denmark
- Department of Clinical Medicine, Faculty of Medicine, Aalborg University, Aalborg, Denmark
- Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark
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Steinsvik EK, Sangnes DA, Søfteland E, Biermann M, Assmus J, Dimcevski G, Gilja OH, Hausken T. Gastric function in diabetic gastroparesis assessed by ultrasound and scintigraphy. Neurogastroenterol Motil 2022; 34:e14235. [PMID: 34378839 DOI: 10.1111/nmo.14235] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/03/2021] [Accepted: 07/07/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Gastroparesis is a severe diabetes complication characterized by delayed gastric emptying. We examined patients with symptoms of diabetic gastroparesis using gastric emptying scintigraphy and ultrasound drink test. The primary aim was to investigate how ultrasound could provide information about gastric motility features in diabetic gastroparesis. MATERIAL AND METHODS We prospectively included 58 patients with diabetes (48 type 1) with symptoms of gastroparesis and 30 healthy controls. Patients were examined with ultrasound of the stomach in a seated position after drinking 500 ml low-caloric meat soup, at the same time recording dyspeptic symptoms. The following day, they were examined with gastric emptying scintigraphy, defining gastroparesis as >10% retention after 4 h. KEY RESULTS We found motility disturbances in the proximal stomach measured by ultrasound in patients with diabetic gastroparesis. A linear mixed effects model including repeated ultrasound measurements revealed a slower decrease of the proximal stomach size in gastroparesis compared to healthy controls (p < 0.01), and the proximal diameter at 20 min was correlated to scintigraphy at 4 h (r = 0.510, p = 0.001). The antrum in patients with diabetic gastroparesis was twice as large compared to healthy controls (p = 0.009), and fasting antral size was correlated to gastric emptying scintigraphy (r = 0.329, p = 0.013). Both diabetes patients with and without gastroparesis had impaired accommodation (p = 0.011). CONCLUSIONS AND INFERENCES On ultrasound, we found delayed reduction of proximal stomach size and impaired accommodation after a liquid meal in patients with gastroparesis, emphasizing the role of the proximal stomach. Furthermore, we found antral distention in gastroparesis patients.
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Affiliation(s)
- Elisabeth K Steinsvik
- National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway.,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Norway
| | - Dag A Sangnes
- National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Norway
| | - Eirik Søfteland
- Department of Clinical Medicine, University of Bergen, Norway.,Hormone Laboratory, Haukeland University Hospital, Bergen, Norway
| | - Martin Biermann
- Centre for nuclear medicine and PET, Department of Radiology, Haukeland University Hospital, Bergen, Norway
| | - Jörg Assmus
- Center for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Norway
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Norway
| | - Trygve Hausken
- National Centre for Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway.,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Norway
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Hansen LEM, Fjelsted CA, Olesen SS, Phillips AE, Faghih M, Wegeberg AM, Drewes AM, Brock C. Simple Quantitative Sensory Testing Reveals Paradoxical Co-existence of Hypoesthesia and Hyperalgesia in Diabetes. FRONTIERS IN PAIN RESEARCH 2022; 2:701172. [PMID: 35295514 PMCID: PMC8915693 DOI: 10.3389/fpain.2021.701172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 06/04/2021] [Indexed: 11/28/2022] Open
Abstract
Background: Diabetic neuropathy is characterized by the paradoxical co-existence of hypo- and hyperalgesia to sensory stimuli. The literature shows consistently sensory differences between healthy and participants with diabetes. We hypothesized that due to differences in pathophysiology, advanced quantitative sensory testing (QST) might reveal sensory discrepancies between type 1 (T1D) and type 2 diabetes (T2D). Furthermore, we investigated whether vibration detection thresholds (VDT) were associated with sensory response. Method: Fifty-six adults with T1D [43 years (28–58)], 99 adults with T2D [65 years (57–71)], and 122 healthy individuals [51 years (34–64)] were included. VDT, pressure pain detection thresholds (pPDT) and tolerance (pPTT), tonic cold pain (hand-immersion in iced water), and central pain mechanisms (temporal summation and conditioned pain modulation) were tested and compared between T1D and T2D. VDT was categorized into normal (< 18 V), intermediary (18–25 V), or high (> 25 V). Results: In comparison to healthy, analysis adjusted for age, BMI, and gender revealed hypoalgesia to tibial (pPDT): p = 0.01, hyperalgesia to tonic cold pain: p < 0.01, and diminished temporal summation (arm: p < 0.01; abdomen: p < 0.01). In comparison to participants with T2D, participants with T1D were hypoalgesic to tibial pPDT: p < 0.01 and pPTT: p < 0.01, and lower VDT: p = 0.02. VDT was not associated with QST responses. Conclusion: Participants with T1D were more hypoalgesic to bone pPDT and pPTT independent of lower VDT, indicating neuronal health toward normalization. Improved understanding of differentiated sensory profiles in T1D and T2D may identify improved clinical endpoints in future trials.
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Affiliation(s)
- Line Elise Møller Hansen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Centre for Clinical Research, North Denmark Regional Hospital, Hjoerring, Denmark
| | - Camilla Ann Fjelsted
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Clinical Institute, Aalborg University, Aalborg, Denmark
| | - Søren Schou Olesen
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Clinical Institute, Aalborg University, Aalborg, Denmark.,Centre of Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Anna Evans Phillips
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
| | - Mahya Faghih
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States
| | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Clinical Institute, Aalborg University, Aalborg, Denmark.,Centre of Pancreatic Diseases, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center Nordjylland, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Clinical Institute, Aalborg University, Aalborg, Denmark.,Steno Diabetes Center Nordjylland, Aalborg, Denmark
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Meling S, Bertoli D, Sangnes DA, Brock C, Drewes A, Ejskjaer N, Dimcevski G, Søfteland E. Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure? Curr Diabetes Rev 2022; 18:e220321192412. [PMID: 34225633 DOI: 10.2174/1573399817666210322154618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/19/2021] [Accepted: 02/13/2021] [Indexed: 11/22/2022]
Abstract
Autonomic neuropathy in patients with diabetes mellitus, and especially complications related to gastrointestinal neuropathy, are often overlooked in the clinic. Diabetic gastroenteropathy affects every segment of the gastrointestinal tract and generates symptoms that may include nausea, early satiety, vomiting, abdominal pain, constipation, and diarrhea. Severe cases can be complicated by weight loss, dehydration, and electrolyte disturbances. The pathophysiology is complex, the diagnostics and treatment options are multidisciplinary, and there is generally a lack of evidence for the treatment options. The aims for this review are first to summarize the pathophysiology and describe possible and expected symptoms and complications.Further, we will try to supply the clinician with a straightforward tool for diagnostics, and then, we shall summarize established treatment options, including diet recommendations, pharmacological and non-pharmacological options. Finally, we will explore the multiple possibilities of novel treatment, looking at medications related to the pathophysiology of neuropathy, other manifestations of autonomic neuropathies, and symptomatic treatment for other gastrointestinal disorders, also including new knowledge of endosurgical and neuromodulatory treatment. The overall goal is to increase awareness and knowledge on this frequent diabetic complication and to provide better tools for diagnosis and treatment. Ultimately, we hope to encourage further research in this field, as there are clear shortcomings in terms of biomarkers, pathophysiology, as well as treatment possibilities. In conclusion, diagnosis and management of diabetic gastroenteropathy are challenging and often require multidisciplinary teams and multimodal therapies. Treatment options are sparse, but new pharmacological, endoscopic, and neuromodulatory techniques have shown promising results in initial studies.
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Affiliation(s)
- Sondre Meling
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Davide Bertoli
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Dag A Sangnes
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Christina Brock
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Asbjørn Drewes
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Jutland, Aalborg, Denmark
- Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Eirik Søfteland
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Sangnes DA, Dimcevski G, Frey J, Søfteland E. Diabetic diarrhoea: A study on gastrointestinal motility, pH levels and autonomic function. J Intern Med 2021; 290:1206-1218. [PMID: 34089624 DOI: 10.1111/joim.13340] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Chronic diarrhoea is a common, but poorly investigated diabetes complication. Autonomic neuropathy is a leading pathophysiological theory founded on old, small studies. Studies of gastrointestinal motility and pH levels are lacking. OBJECTIVES Using new diagnostic methods, we aimed to find out if diabetic diarrhoea was associated with alterations in gastrointestinal motility, pH levels and autonomic function. METHODS Fifty-seven patients (42 women, 46 with type 1 diabetes) were prospectively included. Symptoms were evaluated with the gastrointestinal symptom rating scale, defining ≥4 points as cases with diarrhoea. Patients scoring <4 were used as controls. We used the wireless motility capsule to measure gastrointestinal transit times, pH levels and contractility parameters. Autonomic function was assessed by measuring heart rate variability, baroreflex sensitivity and orthostatic hypotension. RESULTS Seventeen patients (30%) had diarrhoea. Compared with controls, cases had slower gastric emptying (21:46 vs. 4:14, h:min, p = 0.03) and faster colonic transit (18:37 vs. 54:25, p < 0.001). Cases had increased intraluminal pH in the antrum (2.4 vs. 1.2, p = 0.009), caecum (7.3 vs. 6.4, p = 0.008) and entire colon (7.1 vs. 6.7, p = 0.05). They also had a decreased pH difference across the pylorus (3.3 vs. 4.9, p = 0.004) and ileocaecal junction (0.6 vs 1.0, p = 0.009). The groups did not differ in autonomic function, but diastolic blood pressure drop correlated rs = -0.34 (p = 0.04) with colonic transit time. CONCLUSIONS Patients with diabetic diarrhoea had altered gastrointestinal transit and intraluminal pH levels, but minimal changes in autonomic function. Our results suggest that tests of gastrointestinal function are clinically useful in diabetic diarrhoea.
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Affiliation(s)
- Dag A Sangnes
- Department of Medicine, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway.,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Jakub Frey
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway.,Hormone Laboratory, Haukeland University Hospital, Bergen, Norway
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Brock C, Liao D, Wegeberg AM, Mohr Drewes A. The antroduodenal transition time is prolonged in adults with type 1 diabetes. Neurogastroenterol Motil 2021; 33:e14144. [PMID: 33881203 DOI: 10.1111/nmo.14144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 02/22/2021] [Accepted: 03/16/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND The gastroparetic syndrome encompasses antral hypomotility, gastric dysrhythmia, impaired antroduodenal coordination, pyloric dysfunction, and abnormal duodenal motility; the last three collectively referred to as pylorospasms. We hypothesized that antroduodenal motility is diminished and transition time is prolonged in adults with type 1 diabetes (T1D) and polyneuropathy. METHODS This cross-sectional study included 124 participants, of which 21 were healthy, 53 had T1D and 50 had T1D with distal symmetrical polyneuropathy (T1D + DSPN). We used the wireless motility capsule to assess antroduodenal transition time, gastric emptying time, gastric and small bowel motility indices (MI), and numbers of alkalic/acidic exposures. RESULTS In comparison with controls, patients with T1D had prolonged antroduodenal transition time (1.85±1.5 vs. 6.6±4.8 minutes; p=0.02), which was even more pronounced in patients with T1D+DSPN (1.85±1.5 vs. 17.8±28.5 minutes; p<0.008. T1D+DSPN tended to have diminished gastric MI (11.9±2.4 vs. 12.7±1.0, p=0.07) and small bowel MI (13.1±1.4 vs. 13.6±0.6, p=0.05) and experienced more antral/pyloric alkalic episodes (1.2±1.3 vs. 2.0±2.1, p=0.02) compared with controls. CONCLUSION The current method may assess a proxy for severity of pylorospasms in patients with diabetes and other diseases associated with upper gastrointestinal motility disorders, which ultimately may optimize future management.
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Affiliation(s)
- Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Clinical Institute, Aalborg University, Aalborg, Denmark.,Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
| | - Donghua Liao
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Clinical Institute, Aalborg University, Aalborg, Denmark.,Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark
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9
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Anoop S, Dasgupta R, Jebasingh FK, Ramachandran R, Kurian ME, Rebekah G, Balsubramanian KA, Thomas N. Exocrine pancreatic insufficiency related fat malabsorption and its association with autonomic neuropathy in Asian Indians with type 2 diabetes mellitus. Diabetes Metab Syndr 2021; 15:102273. [PMID: 34520998 DOI: 10.1016/j.dsx.2021.102273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/31/2021] [Accepted: 09/02/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS We aimed to estimate the prevalence of exocrine pancreatic insufficiency (EPI) related fat malabsorption & to correlate it with measures of autonomic neuropathy in patients with T2DM from India. METHODS Patients with T2DM (cases; n = 118) and normo-glycaemic individuals (controls; n = 82) underwent anthropometry and biochemical evaluation at baseline. The 72-hours fecal fat excretion was estimated by the Van de Kamer's titration method. Autonomic neuropathy was evaluated using an automated analyzer. RESULTS The prevalence of EPI related fat malabsorption in cases was 45% (n = 53; 72 hours mean fecal fat level = 22.7 ± 5.6 g/day). Dysfunctions in the parasympathetic nervous system (PNS; 86.7%; p < 0.05), sympathetic nervous system (SNS; 92.4%; p < 0.05), and both; PNS + SNS (83.1%; p < 0.05) were significant. Amongst measures of PNS dysfunction, there was a significantly higher percentage of abnormal expiration: inspiration ratio (45.3%) and the 30:15 ratio (84.9%) (p < 0.05) in patients with T2DM and EPI related fat malabsorption. CONCLUSION In this cross-sectional cohort of Asian Indian patients with T2DM (n = 118), EPI related fat malabsorption correlates significantly with autonomic dysfunction in patients with T2DM. However, these preliminary data need to confirmed in trials with more robust design.
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Affiliation(s)
- Shajith Anoop
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
| | - Riddhi Dasgupta
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
| | - Felix K Jebasingh
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
| | - Roshna Ramachandran
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India
| | | | - Grace Rebekah
- Department of Biostatistics, Christian Medical College, Vellore, India
| | - K A Balsubramanian
- Division of Gastrointestinal Sciences, Wellcome Research Laboratory, Christian Medical College, Vellore, India
| | - Nihal Thomas
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.
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Kornum DS, Terkelsen AJ, Bertoli D, Klinge MW, Høyer KL, Kufaishi HHA, Borghammer P, Drewes AM, Brock C, Krogh K. Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives. J Clin Med 2021; 10:jcm10071392. [PMID: 33807256 PMCID: PMC8037288 DOI: 10.3390/jcm10071392] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/25/2021] [Accepted: 03/27/2021] [Indexed: 11/16/2022] Open
Abstract
The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
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Affiliation(s)
- Ditte S. Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
- Correspondence:
| | - Astrid J. Terkelsen
- Department of Neurology, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
| | - Mette W. Klinge
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
| | - Katrine L. Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
| | - Huda H. A. Kufaishi
- Steno Diabetes Centre Copenhagen, Gentofte Hospital, DK2820 Gentofte, Denmark;
| | - Per Borghammer
- Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Asbjørn M. Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
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11
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Bencsik P, Gömöri K, Szabados T, Sántha P, Helyes Z, Jancsó G, Ferdinandy P, Görbe A. Myocardial ischaemia reperfusion injury and cardioprotection in the presence of sensory neuropathy: Therapeutic options. Br J Pharmacol 2020; 177:5336-5356. [PMID: 32059259 PMCID: PMC7680004 DOI: 10.1111/bph.15021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 01/29/2020] [Accepted: 01/29/2020] [Indexed: 12/12/2022] Open
Abstract
During the last decades, mortality from acute myocardial infarction has been dramatically reduced. However, the incidence of post-infarction heart failure is still increasing. Cardioprotection by ischaemic conditioning had been discovered more than three decades ago. Its clinical translation, however, is still an unmet need. This is mainly due to the disrupted cardioprotective signalling pathways in the presence of different cardiovascular risk factors, co-morbidities and the medication being taken. Sensory neuropathy is one of the co-morbidities that has been shown to interfere with cardioprotection. In the present review, we summarize the diverse aetiology of sensory neuropathies and the mechanisms by which these neuropathies may interfere with ischaemic heart disease and cardioprotective signalling. Finally, we suggest future therapeutic options targeting both ischaemic heart and sensory neuropathy simultaneously. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.
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Affiliation(s)
- Péter Bencsik
- Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, Faculty of MedicineUniversity of SzegedSzegedHungary
- Pharmahungary GroupSzegedHungary
| | - Kamilla Gömöri
- Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, Faculty of MedicineUniversity of SzegedSzegedHungary
- Pharmahungary GroupSzegedHungary
| | - Tamara Szabados
- Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, Faculty of MedicineUniversity of SzegedSzegedHungary
- Pharmahungary GroupSzegedHungary
| | - Péter Sántha
- Department of Physiology, Faculty of MedicineUniversity of SzegedSzegedHungary
| | - Zsuzsanna Helyes
- Department of Pharmacology and Pharmacotherapy, Medical SchoolUniversity of PécsPécsHungary
- Molecular Pharmacology Research Group, Centre for Neuroscience, János Szentágothai Research CentreUniversity of PécsPécsHungary
| | - Gábor Jancsó
- Department of Physiology, Faculty of MedicineUniversity of SzegedSzegedHungary
| | - Péter Ferdinandy
- Pharmahungary GroupSzegedHungary
- Department of Pharmacology and PharmacotherapySemmelweis UniversityBudapestHungary
| | - Anikó Görbe
- Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, Faculty of MedicineUniversity of SzegedSzegedHungary
- Pharmahungary GroupSzegedHungary
- Department of Pharmacology and PharmacotherapySemmelweis UniversityBudapestHungary
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12
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Bianchetti G, Spirito MD, Maulucci G. Unsupervised clustering of multiparametric fluorescent images extends the spectrum of detectable cell membrane phases with sub-micrometric resolution. BIOMEDICAL OPTICS EXPRESS 2020; 11:5728-5744. [PMID: 33149982 PMCID: PMC7587257 DOI: 10.1364/boe.399655] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/09/2020] [Accepted: 07/23/2020] [Indexed: 05/08/2023]
Abstract
Solvatochromic probes undergo an emission shift when the hydration level of the membrane environment increases and are commonly used to distinguish between solid-ordered and liquid-disordered phases in artificial membrane bilayers. This emission shift is currently limited in unraveling the broad spectrum of membrane phases of natural cell membranes and their spatial organization. Spectrally resolved fluorescence lifetime imaging can provide pixel-resolved multiparametric information about the biophysical state of the membranes, like membrane hydration, microviscosity and the partition coefficient of the probe. Here, we introduce a clustering based analysis that, leveraging the multiparametric content of spectrally resolved lifetime images, allows us to classify through an unsupervised learning approach multiple membrane phases with sub-micrometric resolution. This method extends the spectrum of detectable membrane phases allowing to dissect and characterize up to six different phases, and to study real-time phase transitions in cultured cells and tissues undergoing different treatments. We applied this method to investigate membrane remodeling induced by high glucose on PC-12 neuronal cells, associated with the development of diabetic neuropathy. Due to its wide applicability, this method provides a new paradigm in the analysis of environmentally sensitive fluorescent probes.
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Affiliation(s)
- Giada Bianchetti
- Fondazione Policlinico Gemelli IRCSS, 00168
Rome, Italy
- Neuroscience Department, Biophysics
Section, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Marco De Spirito
- Fondazione Policlinico Gemelli IRCSS, 00168
Rome, Italy
- Neuroscience Department, Biophysics
Section, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giuseppe Maulucci
- Fondazione Policlinico Gemelli IRCSS, 00168
Rome, Italy
- Neuroscience Department, Biophysics
Section, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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13
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Sierra-Silvestre E, Somerville M, Bisset L, Coppieters MW. Altered pain processing in patients with type 1 and 2 diabetes: systematic review and meta-analysis of pain detection thresholds and pain modulation mechanisms. BMJ Open Diabetes Res Care 2020; 8:8/1/e001566. [PMID: 32868312 PMCID: PMC7462232 DOI: 10.1136/bmjdrc-2020-001566] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 06/24/2020] [Accepted: 07/06/2020] [Indexed: 12/15/2022] Open
Abstract
The first signs of diabetic neuropathy typically result from small-diameter nerve fiber dysfunction. This review synthesized the evidence for small-diameter nerve fiber neuropathy measured via quantitative sensory testing (QST) in patients with diabetes with and without painful and non-painful neuropathies. Electronic databases were searched to identify studies in patients with diabetes with at least one QST measure reflecting small-diameter nerve fiber function (thermal or electrical pain detection threshold, contact heat-evoked potentials, temporal summation or conditioned pain modulation). Four groups were compared: patients with diabetes (1) without neuropathy, (2) with non-painful diabetic neuropathy, (3) with painful diabetic neuropathy and (4) healthy individuals. Recommended methods were used for article identification, selection, risk of bias assessment, data extraction and analysis. For the meta-analyses, data were pooled using random-effect models. Twenty-seven studies with 2422 participants met selection criteria; 18 studies were included in the meta-analysis. Patients with diabetes without symptoms of neuropathy already showed loss of nerve function for heat (standardized mean difference (SMD): 0.52, p<0.001), cold (SMD: -0.71, p=0.01) and electrical pain thresholds (SMD: 1.26, p=0.01). Patients with non-painful neuropathy had greater loss of function in heat pain threshold (SMD: 0.75, p=0.01) and electrical stimuli (SMD: 0.55, p=0.03) compared with patients with diabetes without neuropathy. Patients with painful diabetic neuropathy exhibited a greater loss of function in heat pain threshold (SMD: 0.55, p=0.005) compared with patients with non-painful diabetic neuropathy. Small-diameter nerve fiber function deteriorates progressively in patients with diabetes. Because the dysfunction is already present before symptoms occur, early detection is possible, which may assist in prevention and effective management of diabetic neuropathy.
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Affiliation(s)
- Eva Sierra-Silvestre
- School of Allied Health Sciences, Griffith University, Gold Coast, Queensland, Australia
- Faculty of Human Movement Sciences, Free University Amsterdam, Amsterdam, The Netherlands
| | - Mari Somerville
- School of Allied Health Sciences, Griffith University, Gold Coast, Queensland, Australia
| | - Leanne Bisset
- School of Allied Health Sciences, Griffith University, Gold Coast, Queensland, Australia
- Menzies Health Institute Queensland, Griffith University, Nathan, Queensland, Australia
| | - Michel W Coppieters
- Menzies Health Institute Queensland, Griffith University, Nathan, Queensland, Australia
- Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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14
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Abstract
Gastrointestinal (GI) pain - a form of visceral pain - is common in some disorders, such as irritable bowel syndrome, Crohn's disease and pancreatitis. However, identifying the cause of GI pain frequently represents a diagnostic challenge as the clinical presentation is often blurred by concomitant autonomic and somatic symptoms. In addition, GI pain can be nociceptive, neuropathic and associated with cancer, but in many cases multiple aetiologies coexist in an individual patient. Mechanisms of GI pain are complex and include both peripheral and central sensitization and the involvement of the autonomic nervous system, which has a role in generating the symptoms that frequently accompany pain. Treatment of GI pain depends on the precise type of pain and the primary disorder in the patient but can include, for example, pharmacological therapy, cognitive behavioural therapies, invasive surgical procedures, endoscopic procedures and lifestyle alterations. Owing to the major differences between organ involvement, disease mechanisms and individual factors, treatment always needs to be personalized and some data suggest that phenotyping and subsequent individual management of GI pain might be options in the future.
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15
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Kong Y, Cheng L, Ma L, Li H, Cheng B, Zhao Y. Norepinephrine protects against apoptosis of mesenchymal stem cells induced by high glucose. J Cell Physiol 2019; 234:20801-20815. [PMID: 31032949 DOI: 10.1002/jcp.28686] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Revised: 03/19/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023]
Abstract
In diabetes, the number of bone mesenchymal stem cells (MSCs) decreases and their differentiation is impaired. However, the exact mechanism is unclear. Patients with diabetes often experience sympathetic nerve injury. Norepinephrine (NE), a major mediator of the sympathetic nervous system, influences rat MSC migration in culture and in vivo. The present study aimed to investigate the effect of NE on MSCs under high glucose conditions; therefore MSCs were treated with high glucose and NE. High glucose-induced MSCs apoptosis, which was reversed by NE. To verify the effect of NE, mice underwent sympathectomy and were used to establish a diabetic model. Diabetic mice with sympathectomy had a higher apoptosis rate and higher levels of reactive oxygen species in their bone marrow-derived cells than diabetic mice without sympathectomy. High glucose inhibited p-AKT production and B-Cell CLL/Lymphoma 2 expression, and promoted BAX and caspase-3 expression. NE reversed these effects of high glucose. An AKT inhibitor enhanced the effects of high glucose. Thus, NE had a protective effect on MSC apoptosis induced by high glucose, possibly via the AKT/BCL-2 pathway.
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Affiliation(s)
- Yanan Kong
- Department of Plastic Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Liuhanghang Cheng
- Department of Plastic Surgery and Burn Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
| | - Li Ma
- Department of Plastic Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China
| | - Haihong Li
- Department of Plastic Surgery and Burn Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China
| | - Biao Cheng
- Guangzhou School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China
- Department of Plastic Surgery, General Hospital of Southern Theater Command, PLA, Guangzhou, Guangdong, People's Republic of China
- The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area, PLA, Guangzhou, Guangdong, People's Republic of China
| | - Yu Zhao
- Department of Plastic Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China
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16
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Meldgaard T, Keller J, Olesen AE, Olesen SS, Krogh K, Borre M, Farmer A, Brock B, Brock C, Drewes AM. Pathophysiology and management of diabetic gastroenteropathy. Therap Adv Gastroenterol 2019; 12:1756284819852047. [PMID: 31244895 PMCID: PMC6580709 DOI: 10.1177/1756284819852047] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/26/2019] [Indexed: 02/04/2023] Open
Abstract
Polyneuropathy is a common complication to diabetes. Neuropathies within the enteric nervous system are associated with gastroenteropathy and marked symptoms that severely reduce quality of life. Symptoms are pleomorphic but include nausea, vomiting, dysphagia, dyspepsia, pain, bloating, diarrhoea, constipation and faecal incontinence. The aims of this review are fourfold. First, to provide a summary of the pathophysiology underlying diabetic gastroenteropathy. Secondly to give an overview of the diagnostic methods. Thirdly, to provide clinicians with a focussed overview of current and future methods for pharmacological and nonpharmacological treatment modalities. Pharmacological management is categorised according to symptoms arising from the upper or lower gut as well as sensory dysfunctions. Dietary management is central to improvement of symptoms and is discussed in detail, and neuromodulatory treatment modalities and other emerging management strategies for diabetic gastroenteropathy are discussed. Finally, we propose a diagnostic/investigation algorithm that can be used to support multidisciplinary management.
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Affiliation(s)
| | - Jutta Keller
- Israelitic Hospital in Hamburg, Academic
Hospital University of Hamburg, Germany
| | - Anne Estrup Olesen
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Søren Schou Olesen
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Denmark
| | - Mette Borre
- Department of Hepatology and Gastroenterology,
Aarhus University Hospital, Denmark
| | - Adam Farmer
- Department of Gastroenterology, University
Hospitals of North Midlands, Stoke on Trent, Staffordshire, UK,Centre for Digestive Diseases, Blizard
Institute of Cell and Molecular Science, Wingate Institute of
Neurogastroenterology, Barts and the London School of Medicine and
Dentistry, Queen Mary University of London, UK
| | - Birgitte Brock
- Department of Clinical Research, Steno Diabetes
Center Copenhagen (SDCC), Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and
Hepatology and Department of Clinical Medicine, Aalborg University Hospital,
Denmark,Department of Clinical Medicine, Aalborg
University, Denmark
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17
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Chakraborty S, Halland M, Burton D, Desai A, Neja B, Low P, Singer W, Camilleri M, Zinsmeister AR, Bharucha AE. GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist. J Clin Endocrinol Metab 2019; 104:1967-1977. [PMID: 30358871 PMCID: PMC6467444 DOI: 10.1210/jc.2018-01623] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 10/19/2018] [Indexed: 12/15/2022]
Abstract
CONTEXT Delayed gastric emptying (GE) is common but often asymptomatic in diabetes. The relationship between symptoms, glycemia, and neurohormonal functions, including glucagonlike peptide 1 (GLP-1), are unclear. OBJECTIVES To assess whether GE disturbances, symptoms during a GE study, and symptoms during enteral lipid infusion explain daily symptoms and whether GLP-1 mediates symptoms during enteral lipid infusion. DESIGN In this randomized controlled trial, GE, enteral lipid infusion, gastrointestinal (GI) symptoms during these assessments, autonomic functions, glycosylated hemoglobin (HbA1c), and daily GI symptoms (2-week Gastroparesis Cardinal Symptom Index diary) were evaluated. During enteral lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo. SETTING Single tertiary referral center. PARTICIPANTS 24 healthy controls and 40 patients with diabetic gastroenteropathy. MAIN OUTCOME MEASURES GE, symptoms during enteral lipid infusion, and the effect of exendin 9-39 on the latter. RESULTS In patients, GE was normal (55%), delayed (33%), or rapid (12%). During lipid infusion, GI symptoms tended to be greater (P = 0.06) in patients with diabetes mellitus (DM) than controls; exendin 9-39 did not affect symptoms. The HbA1c was inversely correlated with the mean symptom score during the GE study (r = -0.46, P = 0.003) and lipid infusion (r = -0.47, P < 0.01). GE and symptoms during GE study accounted for 40% and 32%, respectively, of the variance in daily symptom severity and quality of life. CONCLUSIONS In DM gastroenteropathy, GE and symptoms during a GE study explain daily symptoms. Symptoms during enteral lipid infusion were borderline increased but not reduced by a GLP-1 antagonist.
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Affiliation(s)
| | - Magnus Halland
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Duane Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Anshuman Desai
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Bridget Neja
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Phillip Low
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
| | | | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alan R Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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18
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Wegeberg AML, Meldgaard T, Hyldahl S, Jakobsen PE, Drewes AM, Brock B, Brock C. Quantities of comorbidities affects physical, but not mental health related quality of life in type 1 diabetes with confirmed polyneuropathy. World J Diabetes 2019; 10:87-95. [PMID: 30788046 PMCID: PMC6379728 DOI: 10.4239/wjd.v10.i2.87] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 01/16/2019] [Accepted: 02/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND A large number of adults with long-term type 1 diabetes are affected by symmetrical peripheral neuropathy. These complications increase socioeconomic expenses and diminish the individual quality of life. The 36-Item Short Form Health Survey (SF-36) is a generic patient reported questionnaire, measuring mental and physical health related quality of life. We hypothesized that diabetic neuropathy would decrease physical and mental quality of life measured with SF-36, and that clinical appearance may be associated with the decline.
AIM To investigate if diabetic neuropathy would decrease physical and mental quality of life measured with SF-36, and if clinical appearance may be associated with the decline.
METHODS Forty-eight adults [age 50 ± 9 years, 10 females, disease duration 32 (14-51) years] with verified diabetic symmetrical peripheral neuropathy and 21 healthy participants (age 51 ± 6 years, 6 females) underwent standardised nerve conduction testing and completed the SF-36 questionnaire. Furthermore, disease duration, number of comorbidities, both diabetes related and nondiabetes related, vibration perception threshold, number of hypoglycaemic events, HbA1c and administration way of insulin was notified.
RESULTS In comparison to healthy subjects, patients’ mental composite score was not significantly diminished (51.9 ± 8.9 vs 53.1 ± 5.5, P = 0.558), while the physical composite score was (46.3 ± 11.7 vs 54.6 ± 3.3, P = 0.002). As expected, the overall physical health related symptoms in patients were associated to total number of comorbidities (P < 0.0001), comorbidities relation to diabetes (P = 0.0002) and HbA1c (P = 0.005) as well as comorbidities not related to diabetes (P = 0.0006).
CONCLUSION The finding of this study emphasises the importance of focusing on quality of life in adults with diabetes and especially in those with multiple comorbidities as well as the possibility of HbA1c as a biomarker for severe complication.
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Affiliation(s)
- Anne-Marie L Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg 9000, Denmark
| | - Theresa Meldgaard
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg 9000, Denmark
| | - Sofie Hyldahl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg 9000, Denmark
| | - Poul Erik Jakobsen
- Steno Diabetes Center North Judland, Region Nordjylland, Aalborg 9000, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg 9000, Denmark
- Steno Diabetes Center North Judland, Region Nordjylland, Aalborg 9000, Denmark
| | - Birgitte Brock
- Steno Diabetes Center Copenhagen, Region Hovedstaden, Gentofte 2820, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital and Clinical Institute, Aalborg University, Aalborg 9000, Denmark
- Department of Pharmacotherapy and Development, University of Copenhagen, Copenhagen 1071, Denmark
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19
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Wegeberg AML, Brock C, Brock B, Farmer AD, Hobson AR, Semler JR, Scott SM. Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy. Neurogastroenterol Motil 2018; 30:e13407. [PMID: 30062823 DOI: 10.1111/nmo.13407] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Accepted: 06/12/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto-motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers. METHODS Forty-seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age-matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24-hour heart rate variability testing were evaluated. KEY RESULTS In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = -0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023). CONCLUSIONS AND INFERENCES The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.
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Affiliation(s)
- A-M L Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg and Clinical Institute, Aalborg University, Aalborg, Denmark
| | - C Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg and Clinical Institute, Aalborg University, Aalborg, Denmark.,Department of Pharmacotherapy and Development, University of Copenhagen, Copenhagen, Denmark
| | - B Brock
- Steno Diabetes Centre, Copenhagen, Denmark
| | - A D Farmer
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg and Clinical Institute, Aalborg University, Aalborg, Denmark.,Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, Staffordshire, UK.,Academic Surgical Unit & Neurogastroenterology Group, Centre for Neuroscience and Trauma Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | | | - S M Scott
- Academic Surgical Unit & Neurogastroenterology Group, Centre for Neuroscience and Trauma Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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20
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Jansson RW, Hufthammer KO, Krohn J. Diabetic retinopathy in type 1 diabetes patients in Western Norway. Acta Ophthalmol 2018; 96:465-474. [PMID: 29369506 DOI: 10.1111/aos.13654] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 11/06/2017] [Indexed: 12/15/2022]
Abstract
PURPOSE To describe the prevalence of diabetic retinopathy (DR), associated risk factors and health-related quality of life (HRQoL) in a population-based cohort of patients with type 1 diabetes mellitus (DM1). METHODS All patients underwent a general and ophthalmic examination including seven-field stereo fundus photography for grading of DR and diabetic macular oedema (DMO). Kaplan-Meier survival analyses were performed to evaluate disease progression in relation to diabetes duration, age and year of diabetes onset. HRQoL and its association with DR were assessed by the Medical Outcomes Study Short Form 36 (SF-36) questionnaire. RESULTS A total of 237 DM1 patients were included. Mean age at inclusion was 34 years (range, 4-75 years), and mean diabetes duration was 19 years (range, 5 months-63 years). A total of 145 patients (61%) had DR. Sixty-two patients (26%) had mild, 39 (16%) moderate and 13 (5%) severe nonproliferative DR, while 31 (13%) had proliferative DR. The prevalence of DMO was 8%. The most important risk factors predicting severity of DR were diabetes duration (p < 0.0001) and HbA1c level (p < 0.0001). Neuropathy (p = 0.006), nephropathy (p = 0.004) and male gender (p = 0.02) were also significant predictors of DR. Compared to normative SF-36 data, there was a linear trend of decreasing HRQoL with increasing severity of DR that was statistically significant for the four physical dimension scores. CONCLUSION The prevalence of DR in DM1 was largely within the range of previous reports. Diabetes duration, HbA1c level, neuropathy, nephropathy and male gender were all significant predictors of DR severity. The patients with more severe DR had lower HRQoL.
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Affiliation(s)
- Ragnhild W. Jansson
- Department of Clinical Medicine; Section of Ophthalmology; University of Bergen; Bergen Norway
- Department of Ophthalmology; Haukeland University Hospital; Bergen Norway
| | | | - Jørgen Krohn
- Department of Clinical Medicine; Section of Ophthalmology; University of Bergen; Bergen Norway
- Department of Ophthalmology; Haukeland University Hospital; Bergen Norway
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21
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Teigland T, Iversen MM, Sangnes DA, Dimcevski G, Søfteland E. A longitudinal study on patients with diabetes and symptoms of gastroparesis - associations with impaired quality of life and increased depressive and anxiety symptoms. J Diabetes Complications 2018; 32:89-94. [PMID: 29153755 DOI: 10.1016/j.jdiacomp.2017.10.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2016] [Revised: 10/13/2017] [Accepted: 10/22/2017] [Indexed: 02/07/2023]
Abstract
AIMS To examine patient reported outcomes (PRO) in patients previously assessed for diabetic gastroparesis, and to investigate how symptoms of gastroparesis evolve over time. In addition, to further evaluate outcomes in those with versus without diabetic gastroparesis at baseline. METHODS Thirty-four patients with diabetes and gastrointestinal (GI) symptoms, diagnosed with or without diabetic gastroparesis in 2011-2013, were included in this follow-up study. PRO were measured with the Patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM), 36-Item Short Form Survey (SF-36), Patient assessment of upper gastrointestinal disorders-quality of life (PAGI-QOL) and Hospital Anxiety and Depression Scale (HADS). Demographic factors and clinical variables were also recorded. RESULTS Participants diagnosed with gastroparesis had improved glycemic control (p=0.04) and less GI symptoms (p=0.001), after a follow-up time of 3.2years (mean). Both groups reported severely impaired quality of life (QoL). In total 47% reported symptoms of anxiety, 38% symptoms of depression (scores≥8). GI symptom severity or other PRO could not differentiate between the two groups. CONCLUSIONS Patients diagnosed with diabetic gastroparesis, as well as those with gastroparesis symptoms - but normal gastric emptying, suffer from severely impaired QoL and a high burden of anxiety and depressive symptoms.
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Affiliation(s)
- Tonje Teigland
- Department of Medicine, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway; Faculty of Health and Social Science, Bergen University College, PO Box 7030, N-5020 Bergen, Norway
| | - Marjolein M Iversen
- Faculty of Health and Social Science, Bergen University College, PO Box 7030, N-5020 Bergen, Norway
| | - Dag A Sangnes
- Department of Medicine, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway
| | - Georg Dimcevski
- Department of Medicine, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway
| | - Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, PO Box 1400, N-5021 Bergen, Norway.
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22
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Preoperative quantitative sensory testing (QST) predicting postoperative pain: Image or mirage? Scand J Pain 2017; 15:91-92. [DOI: 10.1016/j.sjpain.2017.01.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Ravages of Diabetes on Gastrointestinal Sensory-Motor Function: Implications for Pathophysiology and Treatment. Curr Gastroenterol Rep 2016; 18:6. [PMID: 26768896 DOI: 10.1007/s11894-015-0481-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Symptoms related to functional and sensory abnormalities are frequently encountered in patients with diabetes mellitus. Most symptoms are associated with impaired gastric and intestinal function. In this review, we discuss basic concepts of sensory-motor dysfunction and how they relate to clinical findings and gastrointestinal abnormalities that are commonly seen in diabetes. In addition, we review techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of sensory-motor function. Such technological advances, while not readily available in the clinical setting, may facilitate stratification and individualization of therapy in diabetic patients in the future. Unraveling the structural, mechanical, and sensory remodeling in diabetes disease is based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The final goal is to increase the understanding of the damage to GI structures and to sensory processing of symptoms, in order to assist clinicians with developing an optimal mechanics based treatment.
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24
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Steinsvik EK, Hausken T, Gilja OH. The ultrasound meal accommodation test in 509 patients with functional gastrointestinal disorders. Scand J Gastroenterol 2016; 51:788-94. [PMID: 26953788 DOI: 10.3109/00365521.2016.1153138] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
AIM The Ultrasound Meal Accommodation Test (UMAT) is a clinical test used to assess gastric accommodation, gastric emptying, and visceral sensitivity. It has been used as a clinical tool at Haukeland University Hospital, Bergen for more than 20 years. MATERIAL AND METHODS Five-hundred and nine patients were retrospectively evaluated, 71% females, and 51% were referred from other hospitals or specialists. The aim was to explore the usefulness of UMAT in patients with suspected functional GI disorders (FGID). RESULTS One hundred and sixty patients were diagnosed with functional dyspepsia (FD), and 154 patients were diagnosed with irritable bowel syndrome (IBS). The overlap between IBS and FD was 41%. In 36% of FD patients, ultrasound assessment showed impaired gastric accommodation. Of 262 patients filling out all required fields for the FD diagnosis (ROMA II and III), 198 (74%) met the criteria for FD, but only 91 (34%) were later diagnosed with FD by an experienced clinician. CONCLUSIONS By combining ultrasonography, the symptom response to a standardized meal, and psychological assessment, the UMAT is useful in diagnosis and management of patients with FGID.
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Affiliation(s)
- Elisabeth K Steinsvik
- a National Centre for Ultrasound in Gastroenterology, Department of Medicine , Haukeland University Hospital , Bergen , Norway ;,b National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway
| | - Trygve Hausken
- a National Centre for Ultrasound in Gastroenterology, Department of Medicine , Haukeland University Hospital , Bergen , Norway ;,b National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway ;,c Department of Clinical Medicine , University of Bergen , Bergen , Norway
| | - Odd Helge Gilja
- a National Centre for Ultrasound in Gastroenterology, Department of Medicine , Haukeland University Hospital , Bergen , Norway ;,b National Centre for Functional Gastrointestinal Disorders, Department of Medicine , Haukeland University Hospital , Bergen , Norway ;,c Department of Clinical Medicine , University of Bergen , Bergen , Norway
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25
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Sangnes DA, Søfteland E, Biermann M, Gilja OH, Thordarson H, Dimcevski G. [Gastroparesis - causes, diagnosis and treatment]. TIDSSKRIFT FOR DEN NORSKE LEGEFORENING 2016; 136:822-6. [PMID: 27221182 DOI: 10.4045/tidsskr.15.0503] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND Gastroparesis is a motility disorder of the stomach. The symptoms are non-specific: nausea and vomiting are most common. Stomach pains, early satiety, postprandial fullness and bloating are also frequent symptoms. Current diagnostic criteria require delayed gastric emptying in the absence of any detectable mechanical obstruction. In this review article we elucidate the causes, assessment and treatment options.MATERIAL AND METHOD Structured article search in Embase and PubMed.RESULTS A number of conditions can lead to gastroparesis. The most frequent somatic cause is diabetes mellitus. Gastroparesis may also be iatrogenically inflicted by means of surgery or drugs. It may be difficult to discriminate between functional dyspepsia and idiopathic gastroparesis. Examination is based on patient history, gastroscopy and measurement of the rate of gastric emptying. Biochemical tests are also relevant for differential diagnosis. The treatment is primarily symptomatic, and consists of dietary measures, fluid therapy, drugs, gastric electrical stimulation, or endoscopic or surgical intervention in the form of insertion of a feeding tube for nutrition and abdominal relief, pyloroplasty or gastrectomy.INTERPRETATION Gastroparesis is a serious motility disorder. The condition may have significant consequences for patients, entailing reduced quality of life, reduced workforce participation and a considerable need for health assistance.
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Affiliation(s)
- Dag A Sangnes
- Gastroenterologisk seksjon Medisinsk avdeling Haukeland universitetssykehus
| | - Eirik Søfteland
- Endokrinologisk seksjon Medisinsk avdeling Haukeland universitetssykehus
| | - Martin Biermann
- Senter for nukleærmedisin og PET Radiologisk avdeling Haukeland universitetssykehus og Klinisk institutt 1 Universitetet i Bergen
| | - Odd Helge Gilja
- Nasjonalt senter for gastroenterologisk ultrasonografi Haukeland universitetssykehus og Klinisk institutt 1 Universitetet i Bergen
| | | | - Georg Dimcevski
- Gastroenterologisk seksjon Medisinsk avdeling Haukeland universitetssykehus og Klinisk institutt 1 Universitetet i Bergen
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26
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Drewes AM, Søfteland E, Dimcevski G, Farmer AD, Brock C, Frøkjær JB, Krogh K, Drewes AM. Brain changes in diabetes mellitus patients with gastrointestinal symptoms. World J Diabetes 2016; 7:14-26. [PMID: 26839652 PMCID: PMC4724575 DOI: 10.4239/wjd.v7.i2.14] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 09/14/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
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.
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27
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Ďurdík P, Vojtková J, Michnová Z, Turčan T, Šujanská A, Kuchta M, Čiljaková M. Pulmonary function tests in type 1 diabetes adolescents with diabetic cardiovascular autonomic neuropathy. J Diabetes Complications 2016; 30:79-84. [PMID: 26597599 DOI: 10.1016/j.jdiacomp.2015.10.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 10/17/2015] [Accepted: 10/19/2015] [Indexed: 01/25/2023]
Abstract
Chronic diabetic complications may afflict all organ tissues including cardiovascular and respiratory system. The aim of the study was to establish if the presence of cardiovascular autonomic neuropathy (CAN) was associated with impaired pulmonary function tests in adolescents with type 1 diabetes (T1D). 46 adolescents with T1D and 25 healthy subjects at the age 15-19years were enrolled to the study. Basic anthropometric data, diabetes onset and duration, plasma glucose and A1c were established. Pulmonary function tests were measured by spirometry and the presence of CAN was examined by heart rate variability. Adolescents with T1D had significantly lower pulmonary function test parameters - FVC (p<0.01), FEV1 (p<0.01), MMEF (p<0.05) and PEFR (p<0.05) compared to the control subjects. In diabetic group, patients with CAN (CAN+, n=19) had significantly lower FVC (p<0.05), FEV1 (p<0.05) and PEFR (p<0.05) compared to patients without CAN (CAN-, n=27). All spirometric parameters were significantly lower in CAN+ subjects compared to healthy controls; however, no significant difference was found in these parameters between CAN- subjects and healthy controls. Spirometric parameters (FVC, FEV1) significantly positively correlated with diabetes onset and body mass index; and negatively correlated with diabetes duration and resting heart rate. Our results indicate that CAN may be associated with reduced pulmonary functions in adolescents with T1D.
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Affiliation(s)
- Peter Ďurdík
- Pediatric Department, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Centre of Experimental and Clinical Respirology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Jarmila Vojtková
- Pediatric Department, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Pediatric Department, University Hospital Martin, Slovakia.
| | | | - Tomáš Turčan
- Pediatric Department, University Hospital Martin, Slovakia
| | - Anna Šujanská
- Pediatric Department, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Centre of Experimental and Clinical Respirology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia
| | - Milan Kuchta
- Department of Pediatrics and Adolescent Medicine, Pavol Jozef Šafárik University in Košice, Faculty of Medicine, Slovakia
| | - Miriam Čiljaková
- Pediatric Department, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia; Centre of Experimental and Clinical Respirology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Slovakia
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Horváth VJ, Putz Z, Izbéki F, Körei AE, Gerő L, Lengyel C, Kempler P, Várkonyi T. Diabetes-related dysfunction of the small intestine and the colon: focus on motility. Curr Diab Rep 2015; 15:94. [PMID: 26374571 DOI: 10.1007/s11892-015-0672-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article.
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Affiliation(s)
- Viktor József Horváth
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary.
| | - Zsuzsanna Putz
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Ferenc Izbéki
- Fejér Megyei Szent György Egyetemi Oktató Kórház, Székesfehérvár, Hungary
| | - Anna Erzsébet Körei
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - László Gerő
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Csaba Lengyel
- 1st Department of Medicine, University of Szeged, Szeged, Hungary
| | - Péter Kempler
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Tamás Várkonyi
- 1st Department of Medicine, University of Szeged, Szeged, Hungary
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29
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Vas PRJ, Sharma S, Rayman G. Distal Sensorimotor Neuropathy: Improvements in Diagnosis. Rev Diabet Stud 2015; 12:29-47. [PMID: 26676660 PMCID: PMC5397982 DOI: 10.1900/rds.2015.12.29] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 04/29/2015] [Accepted: 04/30/2015] [Indexed: 01/01/2023] Open
Abstract
Neurological complications of diabetes are common, affecting up to 50% of people with diabetes. In these patients, diabetic sensorimotor neuropathy (DSPN) is by far the most frequent complication. Detecting DSPN has traditionally been a clinical exercise that is based on signs and symptoms. However, the appearance of morphometric and neurophysiological techniques along with composite scoring systems and new screening tools has induced a paradigm change in the detection and stratification of DSPN and our understanding of its natural history and etiopathogenesis. These newer techniques have provided further evidence that changes in small nerve fiber structure and function precede large fiber changes in diabetes. Although useful, the challenge for the use of these new techniques will be their sensitivity and specificity when widely adopted and ultimately, their ability to demonstrate improvement when pathogenic mechanisms are corrected. Concurrently, we have also witnessed an emergence of simpler screening tools or methods that are mainly aimed at quicker detection of large fiber neuropathy in the outpatient setting. In this review, we have focused on techniques and tools that receive particular attention in the current literature, their use in research and potential use in the clinical environment.
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Affiliation(s)
| | | | - Gerry Rayman
- Ipswich Hospital NHS Trust, Ipswich, United Kingdom
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30
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Søfteland E, Brock C, Frøkjær JB, Simrén M, Drewes AM, Dimcevski G. Rectal sensitivity in diabetes patients with symptoms of gastroparesis. J Diabetes Res 2014; 2014:784841. [PMID: 25136644 PMCID: PMC4130227 DOI: 10.1155/2014/784841] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/07/2014] [Indexed: 02/07/2023] Open
Abstract
In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients.
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Affiliation(s)
- Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- *Eirik Søfteland:
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, 9000 Aalborg, Denmark
| | - Jens B. Frøkjær
- Mech-Sense, Department of Radiology, Aalborg University Hospital, 9000 Aalborg, Denmark
| | - Magnus Simrén
- Institute of Medicine, Department of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Asbjørn M. Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, 9000 Aalborg, Denmark
- Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University, 9000 Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, 5020 Bergen, Norway
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31
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Horváth VJ, Izbéki F, Lengyel C, Kempler P, Várkonyi T. Diabetic gastroparesis: functional/morphologic background, diagnosis, and treatment options. Curr Diab Rep 2014; 14:527. [PMID: 25005121 DOI: 10.1007/s11892-014-0527-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The regulation of gastrointestinal motility mainly involves the smooth muscle, neural (extrinsic and intrinsic), and hormonal elements, the glial cells, and the interstitial cells of Cajal. An orchestrated function of all these components is required for the appropriate propulsive movement of the food in the gastrointestinal tract. Gastroparesis, a pathological slowing-down of gastric emptying, is a result of the damage to the tissue elements involved in the regulation of motility. Gastroparesis is one of the well-known complications of long-standing diabetes mellitus. Although it is rarely a life-threatening complication, it has a deteriorating effect on the quality of life, leads to unpredictable oscillation of the blood glucose level, and increases the time required for the absorption of food and medicines. This review describes the clinical characteristics of diabetic gastroparesis and summarizes the organic and functional motility abnormalities caused by this complication. Finally, the currently available and potential future therapeutic approaches are summarized.
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Affiliation(s)
- Viktor J Horváth
- 1st Department of Medicine, Semmelweis University, Koranyi Sandor utca 2/a, 1081, Budapest, Hungary,
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