| 1. |
- Krarup, Anne L., et al.
(författare)
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Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
- 2011
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 33:10, s. 1113-22
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Tidskriftsartikel (refereegranskat)abstract
- Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment. Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat. Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05). Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).
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| 2. |
- Brock, C., et al.
(författare)
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Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3698-3705
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.RESULTSDiabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P 0.001), and showed diminished amplitude of the N2-P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P 0.001).CONCLUSIONSThis study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.
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| 3. |
- Frokjaer, J. B., et al.
(författare)
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Macrostructural Brain Changes in Patients with Longstanding Type 1 Diabetes Mellitus - a Cortical Thickness Analysis Study
- 2013
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Ingår i: Experimental and Clinical Endocrinology & Diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 121:6, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Longstanding diabetes mellitus (DM) is associated with the risk of complications Methods: 15 patients with longstanding (average 24.6 years) type 1 DM and 20 healthy controls were Results: No differences between patients and controls were found in regard to number of white matter Conclusions: Patients with longstanding type 1 diabetes showed cortical thinning involving sensory
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| 4. |
- Frøkjaer, J B, et al.
(författare)
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Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients.
- 2012
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 24:11
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract.
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| 5. |
- Krarup, Anne L., et al.
(författare)
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Exploration of the effects of gender and mild esophagitis on esophageal pain thresholds in the normal and sensitized state of asymptomatic young volunteers
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Clinical data suggest gender differences in gastrointestinal pain, but very little experimental data exist. Esophageal painful thresholds to mechanical, thermal, electric, and chemical stimuli can be measured with the esophageal multimodal pain model. The aim was to measure the effect of gender and mild esophagitis on esophageal pain perception. Methods Thirty-five healthy asymptomatic volunteers [19 men, median age 29 (22-56 years)] underwent upper GI endoscopy, 24 h pH/impedance measurement, and multimodal esophageal pain stimulation before and after sensitization with acid. Stimulus intensities at painful thresholds were recorded. Key Results Men had higher pain thresholds (PT) to mechanical stimulation (mean volume: men 20.9 +/- 10 mL vs women 15.2 +/- 6.8 mL, P = 0.02) and more men tolerated the maximum acid challenge (58% vs 20%, P = 0.03). There were no differences between genders for PT to 1 thermal stimulation [mean stimulation time (men, women): heat; 20 +/- 5 s vs 21 +/- 6 s or cold; 33.3 +/- 20.1 s vs 20.7 +/- 21.4 s, P > 0.2], 2 electrical current (mean current: men 17.6 +/- 9.2 mA vs women 12.9 +/- 3.7 mA, P = 0.11), or 3 acid volume [median volume: men 200 (20; 200) mL vs women 133 (40; 200) mL, P = 0.2]. Fifteen asymptomatic subjects had mild esophagitis (10 men, all Los Angeles A). There were no differences in esophageal PT between subjects with normal endoscopy or mild esophagitis (all P > 0.3). Conclusions & Inferences The effects of gender and mild esophagitis on esophageal multimodal pain perception have been measured in asymptomatic volunteers. The study suggests that gender, not mild esophagitis, tends to influence mechanical and chemical esophageal pain.
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| 6. |
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| 7. |
- Lelic, D., et al.
(författare)
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Brain networks encoding rectal sensation in type 1 diabetes
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522. ; 237, s. 96-105
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Tidskriftsartikel (refereegranskat)abstract
- Introduction It has been shown that patients with type 1 diabetes mellitus and gastrointestinal (GI) symptoms have abnormal processing of sensory information following stimulation in the oesophagus. In order to find less invasive stimuli to study visceral afferent processing and to further elaborate the gut–brain network in diabetes, we studied brain networks following rectal electrical stimulations. Methods Twelve type 1 diabetes patients with GI symptoms and twelve healthy controls were included. A standard ambulatory 24-h electrocardiography was performed. 122-channel-evoked brain potentials to electrical stimulation in the rectum were recorded. Brain source-connectivity analysis was done. GI symptoms were assessed with the gastroparesis cardinal symptom index and quality of life (QOL) with SF-36. Any changes in brain source connectivity were correlated to duration of the disease, heart beat-to-beat intervals (RRs), clinical symptoms, and QOL of the patients. Results Diabetic patients with GI symptoms showed changes relative to controls in the operculum–cingulate network with the operculum source localized deeper and more anterior (P ⩽ 0.001) and the cingulate source localized more anterior (P = 0.03). The shift of operculum source was correlated with the duration of the disease, severity of GI symptoms, and decreased RR (P < 0.05). The shift of the cingulate source was correlated with the mental QOL (P = 0.04). In healthy controls, the contribution of the cingulate source to the network was higher than the contribution of the operculum source (P ⩽ 0.001), whereas in patients the contribution of the two sources was comparable. Conclusion This study gives further evidence for CNS involvement in diabetes. Since network reorganizations were correlated to GI symptoms, irregularities of rectal-evoked potentials can be viewed as a proxy for abnormal bottom-up visceral afferent processing. The network changes might serve as a biomarker for disturbed sensory visceral processing of GI symptoms in diabetes patients.
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| 8. |
- Lelic, D, et al.
(författare)
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The brain networks encoding visceral sensation in patients with gastrointestinal symptoms due to diabetic neuropathy.
- 2014
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 26:1, s. 46-58
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence points to association between long-term diabetes mellitus and abnormal brain processing. The aim of this study was to investigate central changes due to electrical stimulation in esophagus in patients with upper gastrointestinal (GI) symptoms due to diabetic neuropathy.
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| 9. |
- Olausson, Eva A, et al.
(författare)
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Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin-treated diabetes. Methods On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire. Key Results We included 115 patients with insulin-treated diabetes (median age 53, range 21–69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty-three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001). Conclusions & Inferences A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.
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| 10. |
- Olausson, Eva A, et al.
(författare)
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Postprandial Plasma Glucose Response and Gastrointestinal Symptom Severity in Patients With Diabetic Gastroparesis.
- 2014
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Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 8:4, s. 881-888
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Tidskriftsartikel (refereegranskat)abstract
- Gastroparesis is a well-known diabetic complication. The pathogenesis is not fully understood. However, it is important to early diagnose these patients. This study evaluated the plasma glucose response after a test meal, and gastrointestinal (GI) symptom severity in patients with clinical suspicion of diabetic gastroparesis, and assessed its usefulness to predict gastroparesis. In all, 83 subjects with insulin-treated diabetes mellitus (DM) type 1 and 2 were included; 53 subjects had gastroparesis and 30 had normal gastric emptying determined by gastric scintigraphy. GI symptom severity during the preceding 2 weeks was evaluated with a validated questionnaire. The test meal consisted of 100 g meat, 40 g pasta, 150 g carrot, and 5 g oil. The subjects ingested the meal under fasting conditions, and plasma glucose was followed during 180 minutes. Patients with gastroparesis demonstrated a blunted plasma glucose response after a test meal versus patients with normal gastric emptying (P < .005), reflected by lower maximum increase in plasma glucose response and incremental area under the curve of the plasma glucose, but a similar time to the maximum plasma glucose level. All GI symptoms were more severe in patients with gastroparesis. GI symptom severity had the best discriminative value to identify patients with gastroparesis with an area under the receiver operating curve of 0.83 (optimal cutoff: sensitivity 87%, specificity 80%). Patients with diabetic gastroparesis have a blunted postprandial plasma glucose response. Combining this information with the presence of GI symptoms can help clinicians identify diabetic patients with gastroparesis.
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