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Gastrointestinal disorders in diabetes—could it be pancreatic exocrine insufficiency?

This management algorithm was developed by a multidisciplinary expert panel: Hambling C et al with the support of a grant from Mylan Ltd. See bottom of page for full disclaimer.

 

Assessment-of-gastrointestinal-disorders-in-patients-with-diabetes

Assessment of gastrointestinal disorders in patients with diabetes

Pancreatic exocrine insufficiency in diabetes

  • Pancreatic exocrine insufficiency (PEI) is characterised by a deficiency of three major groups of pancreatic enzymes (amylase, protease, lipase):
    • this results in impaired digestion, with abnormal food breakdown, leading to nutrient malabsorption and malnutrition
  • Some degree of PEI has been reported in 50% people with type 1 and 30–50% people with type 2 diabetes:
    • co-existing PEI in people with either type 1 or type 2 diabetes is likely to be a different clinical entity to pancreatic diabetes (sometimes referred to as type 3c diabetes)
    • 5–10% of people with diabetes in Western populations have type 3c diabetes, or diabetes associated with chronic pancreatitis, which is often misclassified as either type 1 or type 2 diabetes:
      • type 3c diabetes is diabetes due to pancreatic disease or injury so both endocrine and exocrine hormone production are affected

Differential diagnosis

  • Gastrointestinal (GI) symptoms are commonly attributed to GI side-effects of diabetes medications, particularly metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors:
    • if symptoms persist despite stopping the medication or reducing the dose, consider an alternative cause for these symptoms
  • Box 1, below, shows the clinical features suggestive of PEI:
    • steatorrhoea and weight loss typically occur only in severe cases or late-stage disease and their absence does NOT exclude a diagnosis of PEI
    • rectal bleeding and blood in the stool are not due to PEI and should be considered red flag signs warranting specialist referral
    • diarrhoea and scores of 5, 6 or 7 on the Bristol Stool Chart are consistent with PEI
  • A differential diagnosis should consider:
    • conditions associated with diabetes:
      • GI side-effects associated with diabetes medications (see above)
      • autonomic neuropathy affecting the bowel
      • coeliac disease*
    • conditions in the general population and not specific to diabetes:
      • irritable bowel syndrome
      • inflammatory bowel diseases
      • bowel cancer
      • coeliac disease*

*Coeliac disease, although common in the general population, more commonly affects people with type 1 diabetes

Box 1: Main symptoms of pancreatic exocrine insufficiency (PEI) at first presentation

Any combination of the following symptoms may suggest PEI.

 

  • Abdominal pain or discomfort

 

  • Bloating

 

  • Flatulence

 

  • Diarrhoea

 

  • Weight loss

 

  • Steatorrhoea

 

  • Altered glycaemic control in patients with diabetes

 

typically only seen in severe cases or late stage disease

Assessment in primary care

  • Faecal elastase-1 <200 µg/g is suggestive of PEI, with values <100 µg/g indicating more severe disease. A value of 200–250 µg/g is considered borderline with retesting recommended:
    • FE-1 may be reduced in patients diagnosed with coeliac disease or IBS suggesting PEI may be the cause of symptoms in these patients or the patient may have both conditions
    • be aware that this measure can be unreliable if the patient has very loose stools
    • if the patient has persistent, very loose and prolonged stools, refer to GI services
  • Elevated calprotectin levels may be suggestive of inflammatory bowel disease
  • Test for vitamin D deficiency by measuring serum 25 hydroxyvitamin D (25OHD) levels (if available):
    • consult national and local guidelines
    • consider vitamin D replacement therapy alongside pancreatic enzyme replacement therapy (PERT) where indicated in line with guideline recommedations
  • Availability of DEXA scans is variable, but if available, may be warranted as these patients may be at risk of reduced bone mineral density

Referral criteria

  • If clinical history and FE-1 levels indicate PEI and no other underlying cause other than diabetes is present, the patient can be treated in primary care:
    • if the patient does not respond to treatment, refer to specialist (gastroenterologist or diabetologist with an interest in GI disorders/PEI)
  • Where other underlying causes are suspected, refer patients to gastroenterologist for tests such as endoscopic ultrasound to identify pancreatic disease, or other pancreatic imaging:
    • a referral is also appropriate if PEI is suspected but the patient has persistent loose stools that make FE-1 measurements unreliable
  • The following may require specialist referral:
    • unexplained weight loss, gastrointestinal bleeding, raised calprotectin levels, or a clinical history suggestive of gastroparesis

Management

  • Pancreatic enzyme replacement therapy (PERT) should be titrated upwards every 4–6 weeks depending on the patient’s clinical response:
    • take with meals or immediately before eating
    • see BNF for dosage information
    • there is no maximum dose specified as the drug works within the gastrointestinal tract
    • patients should be monitored for clinical response (e.g. improvement in symptoms, weight, nutritional status)
  • Advise on smoking cessation, reducing alcohol intake, and/or vitamin D supplementation if appropriate
  • A healthy diet is recommended—altering fat content in the diet is controversial, therefore, refer patient to a dietician for expert advice

Glycaemic control

  • PERT can affect glycaemic control pathways via:
    • altered action of the hormones leptin and incretins on glucose homeostasis; for example it may improve the incretin response to food and consequently lower blood glucose levels
    • improving absorption of oral diabetes medication
  • The patient’s glycaemic response and blood glucose levels should be checked frequently during treatment as the dose of the diabetes medication may need adjusting (especially sulphonylureas and insulin)

about this management algorithm…

sponsor—

This algorithm has been developed by MGP Ltd,  the publisher of Guidelines, and the expert group was convened by MGP Ltd. Final editorial decisions rested with the Chair. Mylan Ltd had the opportunity to comment on the technical accuracy of this algorithm but the content is independent of and not influenced by Mylan Ltd.

group members

Dr Clare Hambling (Chair, GP with a Special Interest in Diabetes), Professor Mike Cummings (Consultant in Diabetes and Endocrinology), Dr Honor Merriman (GP and CPD Tutor), Julie Widdowson (Nurse Diabetes Educator/Practitioner, Service Lead)

further information

call MGP Ltd (01442 876100)

Date of preparation: April 2018