Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?

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.

Gastric function in diabetic gastroparesis assessed by ultrasound and scintigraphy.

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.

Gastrointestinal transit and contractility in diabetic constipation: A wireless motility capsule study on diabetes patients and healthy controls.

BACKGROUND: Diabetic constipation is traditionally attributed to slow colonic transit, despite limited evidence. More than half of patients find treatment unsatisfactory. To improve treatment, there is a need for better diagnostic understanding of the condition. OBJECTIVE: In this wireless motility capsule study, we aimed to investigate gastrointestinal transit and contractility in diabetes patients with and without constipation, and in healthy controls. METHODS: We prospectively included type 1 or type 2 diabetes patients with gastrointestinal symptoms. Based on the Gastrointestinal Symptom Rating Scale we distinguished into two groups: with constipation and without constipation. Non-diabetic controls were asymptomatic. All were examined with wireless motility capsule, determining transit times and contractility parameters. RESULTS: 57 patients (42 women, 46 with type 1 diabetes) and 26 healthy controls (14 women) were included. We found no difference in transit times between diabetes patients with and without constipation. Compared to healthy controls (35:55, h:min), whole-gut transit was slower in both diabetes patients with constipation (66:15, p = 0.03) and without constipation (71:16, p < 0.001). Small bowel motility index correlated rs  = -0.32 (p = 0.01) with constipation symptoms. CONCLUSIONS: Diabetes patients with constipation had similar transit times as those without constipation. Both groups had slower whole-gut transit than healthy controls. Constipation was associated with reduced small bowel, but not colonic contractility. Our results imply that other mechanisms than slow colonic transit may be more important in the pathogenesis of diabetic constipation.

Diabetic diarrhoea: A study on gastrointestinal motility, pH levels and autonomic function.

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.

Gastroparesis Symptoms Associated with Intestinal Hypomotility: An Explorative Study Using Wireless Motility Capsule.

OBJECTIVE: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. PATIENTS AND METHODS: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). RESULTS: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (rs = -0.31, p = 0.007), small bowel (rs = -0.41, p < 0.001) and colonic (rs = -0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (rs = -0.81, p < 0.001) and mean stomach pressure (rs = -0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (rs = -0.77, p < 0.001) and colon (rs = -0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (rs = -0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (rs = -0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. CONCLUSION: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.

Wireless motility capsule compared with scintigraphy in the assessment of diabetic gastroparesis.

BACKGROUND: Gastroparesis is a potentially severe late complication of diabetes mellitus. Today, delayed gastric emptying (GE) is mandatory for establishing the diagnosis. In this study, we compared wireless motility capsule (WMC) with gastric emptying scintigraphy (GES). METHODS: Seventy-two patients (49 women) with diabetes mellitus (59 type 1) and symptoms compatible with gastroparesis were prospectively included between 2014 and 2018. Patients were simultaneously examined with GES and WMC. Symptoms were assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) questionnaire. All patients were on intravenous glucose-insulin infusion during testing. KEY RESULTS: WMC and GES correlated r = .74, P < .001. Compared to GES, WMC at ordinary cutoff for delayed GE (300 minutes) had a sensitivity of 0.92, specificity 0.73, accuracy 0.80, and Cohen's kappa κ = 0.61 (P < .001). By receiver operating characteristics (ROC), the area under the curve was 0.95 (P < .001). A cutoff value for delayed GE of 385 minutes produced sensitivity 0.92, specificity 0.83, accuracy 0.86, and Cohen's kappa κ = 0.72 (P < .001). Inter-rater reliability for GE time with WMC was r = .996, κ = 0.97, both P < .001. There was no difference in symptom severity between patients with normal and delayed GE. CONCLUSIONS & INFERENCES: Our findings demonstrate the applicability of WMC as a reliable test to assess gastric emptying in diabetic gastroparesis showing very high inter-observer correlation. By elevating the cutoff value for delayed emptying from 300 to 385 minutes, we found higher specificity without reducing sensitivity.

Comparing radiopaque markers and 13C-labelled breath test in diabetic gastroparesis diagnostics.

Purpose: Determining gastric emptying is mandatory in the diagnosis of diabetic gastroparesis. Several methods of investigation exist, but none has proven reliable, inexpensive and accessible. In this study, we aimed to compare gastric emptying of radiopaque markers (ROM) and 13carbon-labelled gastric emptying breath tests for solids (GEBT). We also aimed to determine any association between gastric emptying and patient-reported symptoms, glycemic control and the patients' age, diabetes duration and occurrence of other late complications. Patients and methods: Forty-five patients (30 women, 15 men) with diabetes mellitus types 1 or 2 (40, 5) and symptoms of gastroparesis were examined with ROM and GEBT. All were interviewed, filled out symptom questionnaires and had HbA1c levels measured. Results: Forty percent of patients had delayed gastric emptying of ROM, while 55% had delayed gastric emptying of GEBT. Correlation between ROM and GEBT was not significant. Compared to GEBT, sensitivity for a positive ROM test was 0.52, while specificity was 0.74. In women, we found a higher specificity of 0.92, sensitivity 0.47. Difference in HbA1c between patients with positive and negative results was of borderline significance for both tests. GEBT (r=0.41, P=0.008) correlated with HbA1c. Patients with any late complications of diabetes had higher gastric retention of ROM (P=0.028), while patients with polyneuropathy (P=0.014) and diabetic wounds (P=0.004) had slower emptying with GEBT. None of the methods identified significant associations between gastric emptying and symptom scores, age or diabetes duration. Conclusions: As a measure of gastric emptying, the ROM test has benefits of being affordable and available. Compared to GEBT, the method has low diagnostic reliability. Before continued use, we recommend additional studies validating the test in diabetes patients.

Pathophysiology of idiopathic gastroparesis and implications for therapy.

OBJECTIVES: Idiopathic gastroparesis is a gastric motility disorder characterized by chronic upper gastrointestinal symptoms and delayed gastric emptying without an identifiable underlying condition. This review summarizes recent understanding of the pathophysiology and treatment of idiopathic gastroparesis. MATERIALS AND METHODS: Structured literature search in the PubMed, Embase and ClinicalTrials.gov databases. RESULTS: Idiopathic gastroparesis involves several alterations in gastric motility and sensation, including delayed gastric emptying, altered myoelectrical activity, impaired fundic accommodation, visceral hypersensitivity and disturbances in antropyloroduodenal motility and coordination. Multiple cellular changes have been identified, including depletion of interstitial cells of Cajal (ICC) and enteric nerves, as well as stromal fibrosis. The underlying cause of these changes is not fully understood but may be an immune imbalance, including loss of anti-inflammatory heme-oxygenase-1 positive (HO-1) macrophages. There is currently no causal therapy for idiopathic gastroparesis. The treatment ladder consists of dietary measures, prokinetic and antiemetic medications, and varying surgical or endoscopic interventions, including promising pyloric therapies. There are ongoing trials with several novel medications, raising hopes for future treatment. CONCLUSIONS: Patients with idiopathic gastroparesis present several pathophysiological alterations in the stomach, where depletion of ICC is of special importance. Treatment is currently focused on alleviating symptoms through dietary adjustments, medication or surgical or endoscopic interventions.

A longitudinal study on patients with diabetes and symptoms of gastroparesis - associations with impaired quality of life and increased depressive and anxiety symptoms.

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.

Diagnostic Accuracy of Transabdominal Ultrasound in Chronic Pancreatitis.

The performance of transabdominal ultrasound (US) in chronic pancreatitis (CP) following the advances in US technology made during recent decades has not been explored. Our aim in this prospective study was to evaluate the diagnostic accuracy of modern abdominal US compared with the Mayo score in CP. One hundred thirty-four patients referred for suspected CP were included in the study. Fifty-four patients were assigned the diagnosis CP. After inclusion, transabdominal US was performed. Ductal features (calculi, dilations and caliber variations, side-branch dilations and hyper-echoic duct wall margins) and parenchymal features (calcifications, cysts, hyper-echoic foci, stranding, lobulation and honeycombing) were recorded. Features were counted and scored according to a weighting system defined at the international consensus meeting in Rosemont, Illinois (Rosemont score). Diagnostic performance indices (95% confidence interval) of US were calculated: The unweighted count of features had a sensitivity of 0.69 (0.54-0.80) and specificity of 0.97 (0.90-1). The Rosemont score had a sensitivity of 0.81 (0.69-0.91) and specificity of 0.97 (0.90-1). Exocrine pancreatic failure was most pronounced in Rosemont groups I and II (p < 0.001). We conclude that using both unweighted and weighted scores, the diagnostic accuracy of modern transabdominal US is good. The extent of pancreatic changes detected by the method is correlated with exocrine pancreatic function.

[Gastroparesis - causes, diagnosis and treatment]. / Gastroparese - årsaker, diagnostikk og behandling.

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.