Intractable nausea and vomiting associated with poor glycaemic control in a patient with type 1 diabetesBMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4197 (Published 17 August 2016) Cite this as: BMJ 2016;354:i4197
- S Gururaj Setty,, consultant diabetologist and endocrinologist1,
- Marie-France Kong,, consultant diabetologist2
- 1department of diabetes and endocrinology, Northampton General Hospital, Northampton, UK
- 2department of diabetes and endocrinology, University Hospitals of Leicester NHS Trust, Leicester, UK
- Correspondence to: S G Setty
A 54 year old woman with type 1 diabetes was referred to the diabetes clinic with a four year history of nausea, early satiety, abdominal pain, and intermittent vomiting. In recent months she had experienced intractable nausea and vomiting, requiring frequent admission to hospital. Her glycaemic control was poor, with blood glucose readings in the high teens and frequent severe hypoglycaemic episodes after meals, when she needed help.
She has had diabetes for 45 years, complicated by diabetic retinopathy, peripheral neuropathy, and nephropathy. She has had chronic back pain and depression. She was taking insulin glulisine (quick acting insulin) 15 units with meals and insulin glargine (long acting insulin) 26 units at bedtime. Her other drugs included lansoprazole, atorvastatin, zopiclone, gabapentin, metoclopramide (short term), zomorph, and lactulose. She weighed 68.6 kg and her body mass index was 28 kg/m2. Her blood pressure was 129/78 mm Hg, with no postural drop. Her injection sites were normal and systemic examination unremarkable.
Her glycated haemoglobin (HbA1c) was 11.6% (103 mmol/mol), sodium 133 mmol/L (reference range 133-146), potassium 4.9 mmol/L (3.5-5.3), urea 12.3 mmol/L (2.5-7.8), creatinine 113 µmol/L (60-120), estimated glomerular filtration rate 65 mL/min/1.73 m2 (90-120), and blood glucose 19.3 mmol/L (3.3-6.0). Haemoglobin was 145 g/L (115-165), white cell count 12.1×109/L (4.0-11.0), and platelets 251×109/L (140-400). An upper gastrointestinal endoscopy six months ago found no obstruction or ulceration but showed residual food in the stomach after an eight hour fast (fig 1⇓). An ultrasound scan of the abdomen was normal.
What is the most likely diagnosis and how would you confirm this?
How would you treat an acute presentation?
How would you control symptoms in the long term?
1. What is the most likely diagnosis and how would you confirm this?
Diabetic gastroparesis. Request fasting upper gastrointestinal endoscopy, coeliac screen, thyroid function tests, and gastric emptying studies.
Gastroparesis is a chronic disorder of the stomach in which food empties from the stomach more slowly than normal (delayed gastric emptying) in the absence of a mechanical obstruction.1 Delayed gastric emptying is an under-recognised complication of diabetes. Prevalence is difficult to estimate because of selection bias in cross sectional studies.. Gastroparesis is more common in women (80% of cases) than men (20%) and in patients with long term diabetes.5 Gastrointestinal autonomic damage leads to delayed gastric emptying. Patients maybe asymptomatic or experience mild, moderate, or severe symptoms. Symptoms include nausea (92%), an early feeling of fullness after eating (60%), abdominal bloating (75%), gastro-oesophageal reflux, erratic blood glucose control caused by the mismatch of food absorption and insulin action, vomiting of undigested food (84%), and abdominal pain (70-90%, although dominant symptom only in 18%).5 Gastroparesis tends to follow a relapsing and remitting course6 but relapses increase in severity. Over time the remission periods may get shorter and patients may need recurrent hospital admissions. Severe diabetic gastroparesis is associated with weight loss as a result of reduced energy intake and incapacitating symptoms. Patients may need enteral or parenteral feeding.
Perform appropriate investigations to identify other causes of upper gastrointestinal symptoms. Consider gastric emptying studies to confirm the diagnosis of diabetic gastroparesis. Scintigraphic measurement of emptying of isotopically labelled food is the ideal method for diagnosing diabetic gastroparesis. Scintigraphy is relatively easy to perform and non-invasive. The radiation dose is similar to that received for a single abdominal radiograph.7
Scintigraphic breath testing using 13carbon-octanoate has been used to quantify solid or liquid gastric emptying. It is cheaper and simpler than external scintigraphy, with no risk of irradiation..8
A wireless motility capsule can simultaneously measure amplitudes of phasic pressure, temperature, and pH because it traverses different segments of the gastrointestinal tract. Gastric emptying is characterised by the rapid increase in pH as the capsule enters the alkaline duodenum. Wireless motility capsules have similar sensitivity and specificity to scintigraphy, and offer a non-radioactive, ambulatory alternative.9
Although 13carbon-octanoate breath testing and wireless motility capsules have the advantage of avoiding radiation associated with scintigraphy, further studies are needed before they can be routinely recommended for evaluation of delayed gastric emptying.
2. How would you treat an acute presentation?
Treatment involves intravenous fluids to correct dehydration, antiemetics or prokinetics, and strict blood glucose control.
Severe cases can present with dehydration and electrolyte imbalance, with low potassium and magnesium levels. Suboptimal insulin treatment may also predispose patients to diabetic ketoacidosis. Start intravenous fluid resuscitation, correction of any electrolyte imbalance, and treatment of ketoacidosis.10
Various factors such as hyperglycaemia and drugs—in particular glucagon-like peptide 1 receptor agonists—will slow down gastric emptying.11 Progesterone slows gastric emptying, which may lead to worsening of symptoms during pregnancy and during the luteal phase in premenopausal women. Although gastroparesis may be pharmacologically induced, in some patients it might not be feasible or appropriate to withdraw drugs that could slow gastric emptying.
Glycaemic control plays a crucial role in the management of diabetic gastroparesis. Acute hyperglycaemia slows gastric emptying in people with diabetes mellitus and healthy controls.12 13 14 The gastric antral motility is reduced when blood glucose levels increase to more than 9 mmol/L and reaches a standstill when blood glucose levels increase to more than 15 mmol/L (reference range 12-14). Hyperglycaemia also reduces the efficacy of prokinetic drugs.15 Aim for euglycaemia, by using intravenous insulin infusion during an acute presentation.
Intravenous erythromycin (1-2 mg/kg up to 3 mg/kg over 45 minutes every eight hours) is a good prokinetic drug for acute presentations. Metoclopramide can be used to help with symptoms in acute presentations. Cyclizine can reduce nausea, but it is not ideal because it might delay gastric emptying.
3. How would you control symptoms in the long term?
Dietary advice (small and frequent meals, low fat and low fibre diet), prokinetics, and optimisation of glycaemic control. Improving glycaemic control by changing how glucose lowering drugs are administered is important.
The following dietary steps can improve gastric emptying
Small, frequent meals16
Sitting upright or walking after meals18
Liquid diet might help if anticipating an attack.
The following dietary considerations are important
Energy replete diet
Replacement of nutritional deficiencies
A feeding jejunostomy might be needed for malnourished patients with more than 5% weight loss over three months after a trial of nasojejunal feeding.16
Glycaemic control—Prandial action of insulin can be delayed to match the slow glucose release in gastroparesis by being administered after meals. Insulin pump treatment with dual wave bolus improves glycaemic control and reduces glycaemic variability and number of hospital inpatient bed days in patients with severe diabetic gastroparesis.19
Medication—Drugs that might be used include prokinetics (see table 1), analgesics, and antidepressants.
Current safety concerns about most available prokinetic drugs limit their use, but they can be considered for temporary relief of symptoms.
The Medicines and Healthcare ProductsRegulatory Agency recommends restricting metoclopramide for adults to a maximum of five days at a dose no higher than 10 mg three times daily20 because of the risk of extrapyramidal side effects with long term use.
Domperidone at the lowest effective dose can be considered for the shortest possible duration.21 The European Medicines Agency endorses the use of domperidone 10 mg orally up to three times daily, with caution because of a small risk of a prolonged QT interval.22
Erythromycin causes substantial acceleration of gastric emptying. When used for more than four weeks, however, there is a risk of tachyphylaxis. This is off-label use, as erythromycin does not have marketing authorisation in the United Kingdom for treating gastroparesis. Combination treatment with domperidone and erythromycin should be avoided because of the risk of a prolonged QT interval.23
Suspension or dispersible formulations of drugs have greater efficacy in people with gastroparesis.24
Pain may improve with prokinetic drugs, but some patients might need additional help. Consider weaker opiates such as tramadol, but try and avoid opiates as they can aggravate gastroparesis.25
Antidepressants such as mirtazapine may have advantages in improving symptoms associated with diabetic gastroparesis.26 Consider psychological input where appropriate.
Other options—These include gastroelectrical stimulation and surgery.
Gastroelectrical stimulation may relieve weekly vomiting, and the need for nutritional supplementation, but has not been shown to improve gastric emptying.25 28 The mechanism of action is not well understood. Guidance from the National Institute for Health and Care Excellence states: “Current evidence on the efficacy and safety of gastric electrical stimulation for gastroparesis is adequate to support the use of this procedure with normal arrangements for clinical governance, consent and audit.” NICE recommends that doctors inform patients that not all people benefit from gastroelectrical stimulation.1 27
Surgery is another option. Pyloroplasty should be used rarely, and partial or complete gastrectomy is regarded as a last resort in carefully selected patients because of the associated mortality and morbidity.10 29 Although pyloric injection of botulinum toxin showed initial promise as a potential treatment option, it is not recommended for patients with gastroparesis on the basis of the outcomes of randomised controlled trials.30
The patient was managed conservatively with dietary modifications, anti-emetics, and periods of drug holidays. Her symptoms are well controlled at present.
Competing interests: We have read and understood BMJ policy on declaration of interests and declare: none.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent obtained.