Question from practice: Could you spot diabetic gastroparesis?
Q. I’ve been feeling sick and bloated for a few months now and I seem to feel full really quickly too. A friend said I should come and buy some Motilium tablets. Would they be OK for me to take? I’m diabetic.
A. These symptoms in combination with diabetes can indicate the development of diabetic gastroparesis, a type of neuropathy that can affect patients with either type 1 or type 2 diabetes. The prevalence of neuropathy in patients with diabetes is about 30 per cent.
Hyperglycaemia is a key factor in the pathophysiology of diabetic neuropathy, but other changes also contribute. In type 2 diabetes, dyslipidaemia and disturbances in neuronal insulin sensitivity are thought to play a major role. Changes in insulin signalling are important in patients with type 1 diabetes.
Gastroparesis affects about 40 per cent of patients with longstanding diabetes (usually of at least 10 years)., It is an autonomic neuropathy predominantly characterised by delayed gastric emptying in the absence of mechanical obstruction of the stomach. This results in poor glycaemic control, malnutrition, poor quality of life and hospital admissions.
Symptoms are variable and typically include nausea (92 per cent), vomiting after meals (84 per cent), bloating (75 per cent), postprandial fullness or early satiety (60 per cent), belching and reflux (<50 per cent), and loss of appetite and weight loss (<50 per cent).
Autonomic dysfunction occurs throughout the gastrointestinal tract, and gut dysmotility can result in impaired oral drug absorption as well as constipation (60 per cent) or diarrhoea. Diarrhoea seems to be more common in type 1 than in type 2 diabetes.
Symptoms are more common in patients with poor long-term glycaemic control and psychological disorders. Many patients, however, have no symptoms despite impaired gastric motility.
- Diabetic gastroparesis affects about 40 per cent of patients with long-standing diabetes. It can cause poor glycaemic control and malnutrition.
- It is managed by optimising blood glucose control, nutritional support and prokinetics, but there is limited evidence to support choice.
Diagnosis Diagnosis of gastroparesis is difficult and is often based on exclusion. Patients with suspected diabetic gastroparesis should be referred for a specialist review. There are diagnostic tools available, including the “Diabetes bowel symptom questionnaire”, which has been validated as useful in identifying and quantifying symptoms.
A detailed history should be taken because other possible causes of dysmotility include previous gastric surgery and neurological and rheumatological disorders. Heartburn or use of non-steroidal anti-inflammatory drugs can suggest peptic ulcer disease. Medication with metformin should also be considered as a possible cause of diarrhoea or gastrointestinal upset.
A physical examination typically reveals associated peripheral sensory and autonomic neuropathy, background or advanced retinopathy, a distended gut and the sound of liquid splashing when the abdomen is shaken from side to side. It is essential to rule out obstruction with the use of oesophagogastro-duodenoscopy or a barium study of the stomach.
A range of tests is available to aid diagnosis, but gastric emptying measurement is advised. In patients with normal gut function a solid meal passes through the stomach over three to four hours. Liquids are emptied much faster. The fat and calorie content of a meal can increase or delay the rate of emptying. Gastric hormones, including incretins, are increased by the presence of food in the stomach; these act to slow gastric emptying, allowing delivery of food at a rate that controls postprandial glycaemia.
The standard method for measuring gastric emptying is scintigraphy. This measures the rate at which a solid meal passes through the gut. Measurement of gastric emptying of solids is more sensitive for detecting gastroparesis because liquid emptying may remain normal even in patients with advanced disease. The study must be carried out for at least two hours (ideally four), with results reported as the percentage of a standard meal retained at one, two, three and four hours. There is large interindividual variation, and before the test medicines that may influence gastric emptying should be withdrawn and blood glucose should, ideally, be maintained at <10mmol/l.,
Gastric emptying should be investigated in those with symptoms spanning over several months to years. Although consensus guidelines do not state at what stage patients need to be referred, a high degree of suspicion should be maintained if symptoms are not explained by gastroscopy or if patients have poorly controlled or unstable diabetes.
Treatment Key principles in the management of diabetic gastroparesis include:
- Optimisation of blood glucose
- Provision of nutritional support and correction of electrolyte levels
- Prokinetic and symptomatic therapies
Management can be tailored to the severity of the condition, which is classified according to a patient’s ability to maintain adequate nutrition and responsiveness to therapy. Symptoms of mild disease usually respond to improvements in glycaemic control or minor dietary adjustments. Moderate or severe gastroparesis often requires medication to increase gastric motility, as well as improved glycaemic control and dietary modification.4
More randomised clinical trials are needed to guide decisions about the optimal drug, device and nutritional management of diabetic gastroparesis. Few medicines or other therapies have been studied rigorously for this indication. Guidelines for management have been published by the American Gastroenterological Association7 and the American Motility Society. However, these are predominantly based on expert opinion and experience. The panel gives an overview of treatment according to disease severity.
Medicines that affect gastric emptying should be discontinued where possible. These include opioids, anticholinergic medicines, calcium channel blockers and proton pump inhibitors. In particular, delayed gastric emptying may be caused or exacerbated by antidiabetics, including glucagon-like peptide-1 agonists (eg, exenatide, liraglutide and lixisenatide). Where these medicines are stopped, consideration must be given to potential weight gain and impairment of blood glucose levels.
|Overview of treatment (Adapted from Tesfaye S et al.3)|
|Liquidised food||When symptomatic||When symptomatic||Routine treatment|
|Nutritional supplements||Rarely required||Liquid supplements (eg, Fortisip, Ensure); nasojejunal tube feeding||Nasojejunal tube feeding; percutaneous endoscopic jejunostomy (PEJ) feeding often required|
10mg tds prn
|Metoclopramide 10mg tds with meals; or domperidone 10–20mg tds with meals, possibly with erythromycin 250mg tds and prochlorperazine 25mg prn||Metoclopramide 10mg tds with meals; or domperidone 10–20mg tds with meals, possibly with erythromycin 250mg tds and prochlorperazine 25mg prn or ondansetron 4mg tds (oral or intravenous)|
Blood glucose control The only disease-modifying therapy is glucose control. Loss of glucose control may actually be one of the first indicators of gastroparesis. Hyperglycaemia contributes to symptoms by slowing gastric emptying, even without autonomic neuropathy. Therefore after a diagnosis of diabetic gastroparesis, first-line treatment should concentrate on optimising blood glucose levels.
The rate of gastric emptying is a major determinant of postprandial blood glucose changes. Food residue is retained in the stomach owing to impaired gastric peristalsis and lower intestinal dysmotility.
Delayed gastric emptying can cause otherwise unexplained hypoglycemia in insulin-treated patients, in whom nutrient delivery needs to match the action of the exogenous insulin.
Although there is a lack of clinical trials showing that the restoration of euglycaemia or correction of electrolyte derangements normalises gastric emptying or ameliorates symptoms, clinical experience and observational data suggest that improved metabolic control is beneficial.
Diet Nutritional support depends on symptoms and disease severity. General recommendations rely on measures that promote gastric emptying. For example, increasing the liquid nutrient component of meals can help because liquid emptying is often preserved in patients who have delayed solid emptying. Since fats and fibre tend to slow emptying, it should be recommended that these elements are reduced.
Indigestible fibre may predispose patients to bezoar formation. A bezoar is a solid indigestible mass that accumulates in the gastrointestinal tract. It is important to check for bezoars because these are difficult to lyse during endoscopy and surgery to remove them is associated with a 10 per cent mortality. A low-fibre diet is, therefore, particularly important for patients with gastroparesis.
Meal size should be restricted because the stomach may only empty a given number of calories in a fixed period, and it is often recommended that patients eat small meals four or five times daily. Carbonated beverages release carbon dioxide, and so can aggravate gastric distention; and high levels of alcohol and smoking can also impair gastric emptying.
Indications for enteral supplements include unintentional weight loss or inability to achieve a recommended weight, hospital admission for refractory symptoms and nausea and vomiting affecting quality of life.
Drugs The most commonly used drug therapies are prokinetic treatments. Metoclopramide, domperidone and erythromycin have all been shown in randomised controlled trials to improve symptoms by 25–75 per cent. However there is a lack of head-to-head trials that compare these medicines and the trials themselves are small and often include populations that have gastroparesis caused by other factors, so there is limited evidence to recommend one treatment over another.
Metoclopramide has been associated with a range of neurological side effects, including anxiety, depression and change in cognitive function. Domperidone appears to be comparatively effective and lacks central nervous system side effects so offers some advantage over metoclopramide. However, it is currently subject to a cardiovascular safety review (PJ, 2014;292:283). The benefit of both drugs is that they can also be used to alleviate nausea and vomiting.
Erythromycin increases motility, but there is no evidence for an improvement in symptoms. There is also evidence that patients can become tolerant, so it is often reserved for the use of acute flares of gastroparesis requiring hospital admission., Antiemetic therapies are also used and include prochlorperazine and ondansetron (metoclopramide also has antiemetic properties).
Patients often experience pain due to the neuropathy itself. However, opioids slow gastric emptying, so pain should be treated according to the National Institute for Health and Care Excellence guideline for neuropathic pain, which recommends low-dose antidepressants or gabapentin.
Acupressure, acupuncture, ginger and hypnotherapy have been suggested and although there is limited evidence pharmacists may recommend these remedies to supplement conventional therapy.
Devices The use of gastric electrical stimulation (GES) is based largely on open-label experience, and its mechanism of action is unclear. GES involves the use of electrodes placed in the muscle wall of the stomach. These are connected to a neurostimulator in a pocket of the abdominal wall. There are limited data to support this treatment. NICE issued interventional procedure guidance on the use of GES in 2004. It did not recommend its use due to a lack of evidence for efficacy or safety. Therefore it is only used in the UK in specialist centres as part of research protocols.
This case In this case, the diabetes and gastrointestinal symptoms suggest the possibility of gastroparesis. Any patient that presents with these symptoms and history in the pharmacy should be referred for further investigation. Domperidone should not be supplied; although it may provide symptomatic relief and is a first-line prescribing choice, its provision may prevent the patient from seeking medical advice and may interfere with diagnostic tests.
Following referral, obstruction would need to be ruled out and the diagnosis should be confirmed with scintigraphy to monitor gastric emptying and diagnose severity of the condition. The initial likely therapy would be a prokinetic (eg, metoclopramide 10mg tds before meals) and, if necessary, an antiemetic (eg, prochlorperazine).
Depending on the severity of the diagnosis, a dietitian may be needed to advise the patient on the use of liquid or homogenised meals to supplement oral nutrition. Control of diabetes should be optimised and pharmacists can have an active role in reinforcing advice and medication changes.
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.11137426
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