Objective(s): To understand how plasma concentrations of pancreatic (glucagon, amylin, pancreatic polypeptide (PP), insulin) and gut hormones incretins (Glucagon-like peptide 1 (GLP-1) and Glucose dependent insulinotropic peptide (GIP)) change in relation to fasting and feeding (different types of nutrients) in healthy and hyperinsulinaemic hypoglycaemia (HH) children of different ages.
Methods: Plasma pancreatic and incretin hormone concentrations were determined by immunoassay MILLIPLEX® MAP Kit (Millipore, Watford, UK). Samples were taken during fast (beginning (normoglycaemia) and end of fast (hypoglycaemia in cases, normoglycaemia in controls)) and during stimulation tests: Oral Glucose Tolerance (OGTT)/Mixed Meal (MM). Nine controls and 15 cases (three focal HH (FCHI) and 12 diffuse HH (DCHI)) where analysed during the fast. Six controls and eight cases (N: 4 dumping syndrome, N: 1 idiopathic postprandial HH, N: 2 DCHI, N: 1 atypical HH) were analysed during OGTT/MM tests.
Results: During fast: Amylin decreased in HH cases versus controls where it increased by the end of the test. Insulin remains detectable despite hypoglycaemia, whereas glucagon response is blunted in HH case. The concentrations of PP in HH children do not show a specific pattern in the face of hypoglycaemia. GLP-1 and GIP concentrations are higher in controls than in HH cases, but in all groups, these decrease by the end of the fast. Stimulation tests: In HH cases, MM test triggers a more potent response than OGTT for: glucose, insulin, amylin, PP, GLP-1 and GIP and it does not suppress glucagon. Conversely, in control subjects, it is the OGTT that triggers a more powerful response for all these hormones. Amylins concentrations during stimulation tests are higher in HH cases than in controls. The pattern of PP during OGTT and MM is similar in HH patients to controls. GLP-1 and GIP are similarly released in HH as in controls after OGTT; but released in excess in HH cases following a MM.
Conclusions: In HH cases, amylin may have a protective role to avoid exacerbation of hypoglycaemia and may do so by stimulating food intake. There seems to be little, if any, role of PP in glucose regulation. OGTT/MM results may guide the clinician to decide which test is more suitable for each indication and the role of feed modification to manage HH cases. Blocking the release or action of incretins could potentially benefit HH patients.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology