Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy.

BACKGROUND/AIMS: Patients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms. METHODS: Twenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans. RESULTS: Patients with DM and HCs did not differ with regard to median gastric contraction frequency (DM: 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs: 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM: 9 mm [IQR, 8-11]; HCs: 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM: 149 cm3 [IQR, 112-187]; HCs: 132 cm3 [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM: 3.3 hours [IQR, 2.6-4.6]; HCs: 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM: 5 hours [IQR, 3.7-5.6]; HCs: 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM: 623 cm3 [IQR, 487-766]; HCs: 478 cm3 [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs. CONCLUSION: In our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy.

Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives.

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.

Normative values for region-specific colonic and gastrointestinal transit times in 111 healthy volunteers using the 3D-Transit electromagnet tracking system: Influence of age, gender, and body mass index.

BACKGROUND: The 3D-Transit electromagnet tracking system (Motilis Medica, SA, Lausanne, Switzerland) is an emerging tool for the ambulatory assessment of gastrointestinal (GI) transit and motility. Using this tool, we aimed to derive normative values for region-specific colonic and GI transit times and to assess the influence of age, gender, and body mass index (BMI). METHODS: Regional and total colonic transit times (CTT), gastric emptying (GET), small intestinal (SITT), and whole gut (WGTT) transit times were extracted from 111 healthy volunteers from the United Kingdom and Denmark (58 female; median age: 40 years [range: 21-88]). The effects of age, gender, and BMI were assessed using standard statistical methods. KEY RESULTS: The ascending, transverse, descending, and rectosigmoid colon transit times accounted for 32%, 34%, 17%, and 17% of total CTT in females, and 33%, 25%, 14%, and 28% of total CTT in males. CTT and WGTT were seen to cluster at intervals separated by approximately 24 hours, providing further evidence of the non-continuous nature of these measurements. Increasing age was associated with longer CTT (P = .021), WGTT (P < .001) ascending (P = .004), transverse (P < .001), and total right (P < .001) colon transit times, but shorter rectosigmoid (P = .004) transit time. Female gender was significantly associated with longer transverse (P = .049) and descending (P < .001) colon transit times, but shorter rectosigmoid (P < .001) transit time. Increasing BMI was significantly associated with shorter WGTT (P = .012). CONCLUSIONS AND INFERENCES: For the first time, normative reference values for region-specific colonic transit have been presented. Age, gender, and BMI were seen to have an effect on transit times.

Enteric cholinergic neuropathy in patients with diabetes: Non-invasive assessment with positron emission tomography.

BACKGROUND: 11 C-Donepezil positron emission tomography (PET) allows non-invasive assessment of cholinergic innervation of visceral organs. We aimed to compare cholinergic innervation in the gut in patients with diabetes mellitus (DM) and in healthy controls (HC). METHODS: 11 C-Donepezil PET and computed tomography (CT) were performed in 19 patients with type 1 DM and gastrointestinal symptoms and in 19 age- and sex-matched HC in a cross-sectional design. KEY RESULTS: All patients had severe gastrointestinal symptoms when assessed by standard questionnaires. DM patients had significantly increased volume of the small intestinal wall (DM: median 557 cm3 [interquartile range [IQR] 446-697] vs HC median: 448 cm3 [IQR; 341-518; P < .01]), and the 11 C Donepezil PET uptake was reduced in patients (DM: median 7.08 standardized uptake value [SUV] [IQR; 5.94-8.43] vs HC: median 9.18 SUV [IQR; 8.57-10.11; P < .01]). A similar pattern was found in colon (DM: median volume 1064 cm3 [IQR; 882-1312] vs HC: median 939 cm3 [IQR; 785-1081; P = .13] and DM: median 1.22 SUV (IQR; 1.08-1.36) vs HC: median 1.42 SUV (IQR; 1.32-1.53; P = .03). Furthermore, patients had significantly reduced pancreatic volume (DM: median 53 cm3 [IQR; 41-69] vs HC: median 98 cm3 [IQR;82-110; P < .01]) and reduced PET uptake of the pancreas (DM: median 13.14 SUV [IQR;9.58-15.82] vs HC: median 21.46 SUV [IQR;18.97-24.06; P < .01]) as well as the adrenal gland (DM: median 7.62 SUV [IQR;7.61;15.82] vs HC: median 15.51 SUV [IQR;12.22;19.49; P = .03]). CONCLUSION AND INFERENCES: Assessed with 11 C-Donepezil PET/CT, patients with DM and severe bowel symptoms have reduced cholinergic innervation of the gut indicative of parasympathetic denervation.

Cardiac 11C-Donepezil Binding Increases With Age in Healthy Humans: Potentially Signifying Sigma-1 Receptor Upregulation.

BACKGROUND: Donepezil may have cardioprotective properties, but the mechanism is unclear. Using positron-emission tomography (PET), we explored 11C-donepezil uptake in the heart of humans in relation to age. The results are discussed in the context of the cardioprotective property of donepezil. METHODS: We included data from 57 patients with cardiac 11C-donepezil PET scans. Linear regression analyses were performed to explore the correlation between cardiac 11C-donepezil standardized uptake value (SUV) and age. Subgroup analyses were performed for healthy controls, patients with prodromal or diagnosed Parkinson disease (PD), males, and females. RESULTS: In the total group of 57 patients, linear regression analysis revealed a significant positive correlation between cardiac 11C-donepezil uptake and age ( r2 = .63, P < .0001). The average increase was ≈1.25 SUV per decade and a 2-fold increase in SUV from age 30 to 65 years. Subgroup analyses also showed significant correlations: healthy control patients alone (n = 28, r2 = .73, P < .0001), prodromal or diagnosed PD (n = 29, r2 = .28, P = .03), male patients (n = 34, r2 = .49, P < .0001), and female patients (n = 23, r2 = .82, P < .0001). No other organs showed increased 11C-donepezil binding with age. CONCLUSIONS: 11C-donepezil SUV increases robustly with age in the normal human heart. We speculate that the increased donepezil binding is caused primarily by sigma-1 receptor upregulation. If our interpretation is correct, it shows that sigma-1 receptors are dynamically regulated and may represent an overlooked target for pharmacological intervention studies.

Early Assessment of Cost-effectiveness of Gastric Electrical Stimulation for Diabetic Nausea and Vomiting.

BACKGROUND/AIMS: Recurrent nausea and/or vomiting are common complications of diabetes mellitus. The conditions severely impact the quality of life of patients and often cause repeated admissions to hospital incurring significant healthcare costs. If standard treatment fails, gastric electrical stimulation (GES) may be offered in selected cases, as a minimally invasive, but expensive, therapeutic option. Our aims are to evaluate the clinical effect and the cost-utility of GES as a treatment for severe diabetic recurrent nausea and/or vomiting. METHODS: Among 33 diabetes patients implanted with GES because of recurrent nausea and/or vomiting, 30 were available for evaluation. The effect of treatment was assessed prospectively using symptom-diaries and the SF-36 questionnaires at baseline, after 6 and 12 months, and thereafter yearly. The number of days in hospital due to symptoms related to gastrointestinal dysfunction was calculated using hospital records 12 months prior to and 12 months after implantation. RESULTS: The surgical procedures were performed without mortality or major complications. Six months after surgery 78% of the respondents had at least 50% reduction in time with nausea and 48% had at least 50% reduction in days with vomiting. Symptom relief persisted at follow-up after at least 4 years. Quality adjusted life years improved after GES, which was cost-effective after 24 months. CONCLUSIONS: GES reduces symptoms and improves quality of life in diabetes patients with recurrent nausea and/or vomiting. The procedure is supposed as cost-effective over a 2-year time horizon.