Table 1.

Methods for clinical assessment of pancreatic exocrine and endocrine function

Exocrine function tests
Immunoreactive trypsinogen	Neonatal screening test for CF based on heel prick. Elevated blood levels from impaired pancreatic duct drainage may be seen in carriers of heterozygous CFTR mutations and this test does not distinguish between pancreatic-sufficient and - insufficient CF, so confirmation testing by CFTR mutation analysis and/or sweat testing is required.
CFTR mutation analysis	Class I–III ‘severe’ mutations are associated with pancreatic insufficiency in CF, whereas the presence of at least one class IV–V mutation, resulting in partially functional CFTR, is required for pancreatic-sufficient CF.
Pancreatic faecal elastase	Levels >200 μg elastase/g faecal material are consistent with normal, 100–200 μg elastase/g faecal material indeterminate, and <100 μg elastase/g faecal material insufficient pancreatic exocrine function.
Faecal fat test	Requires 72 h stool collection. Elevated in pancreatic insufficiency due to maldigestion from loss of pancreatic lipase activity but is also elevated by malabsorption in disorders of the small intestine (e.g. coeliac disease, bacterial overgrowth, short bowel syndrome).
Direct pancreatic function test	Requires upper gastrointestinal endoscopy. Measures pancreatic secretion of bicarbonate or lipase into the duodenum following stimulation with i.v. secretin or cholecystokinin (CCK), respectively. More likely to be reduced early in the development of pancreatic exocrine disease than indirect tests (faecal elastase, faecal fat).
Endocrine function tests
HbA1c	Standard screening test with criteria for defining normal (<5.7% [<39 mmol/mol]), increased risk of diabetes (5.7–6.4% [39–47 mmol/mol]) and diabetes (≥6.5% [≥48 mmol/mol]). Less sensitive than OGTT measures in patients with pancreatic exocrine disease.
Fasting glucose	Standard screening test with criteria for defining normal (<5.6 mmol/l [100 mg/dl]), impaired fasting glucose (5.6–6.9 mmol/l [100–125 mg/dl]) and diabetes (≥7.0 mmol/l [126 mg/dl]). Less sensitive than OGTT measures in patients with pancreatic exocrine disease.
2 h OGTT glucose	Standard screening test with criteria for defining normal (<7.8 mmol/l [140 mg/dl]), impaired glucose tolerance (7.8–11.0 mmol/l [140–199 mg/dl]) and diabetes (11.1 mmol/l [≥200 mg/dl]). Consider whenever the HbA1c or fasting glucose indicates increased risk, and use annually in CF to evaluate for the presence of diabetes.
1 h OGTT glucose	Non-standard screening test useful for defining early glucose intolerance (≥8.6 mmol/l [155 mg/dl]) in CF and chronic pancreatitis. Consider including as part of any OGTT performed in individuals with pancreatic disease.
Fasting insulin or C-peptide	Useful with fasting glucose to derive homeostatic model assessment indices of beta cell function (HOMA-B) and insulin resistance (HOMA-IR) that can help to distinguish pancreatogenic from type 2 diabetes.
Stimulated C-peptide	Useful 60 or 90 min after OGTT or MMTT as an estimate of beta cell secretory reserve, in particular as part of the evaluation and follow-up for individuals with chronic pancreatitis considering total pancreatectomy with islet autotransplantation, where outcomes are dependent on isolated and engrafted islet beta cell mass.
Stimulated PP	Useful 60 or 90 min after MMTT as a marker of pancreatic disease affecting islet function. In the presence of diabetes, an absent PP response is a specific indicator of pancreatogenic diabetes.

CF, cystic fibrosis; OGTT, oral glucose tolerance test, standard 1.75 g/kg up to 75 g ingested over 5 min; MMTT, mixed-meal tolerance test, standard 6 ml/kg up to 360 ml (12 ounces) Boost High Protein or equivalent ingested over 5 min (with prescribed pancreatic enzymes for those with established pancreatic exocrine insufficiency).