Pancreatic beta-cell stimulation tests in transient and persistent congenital hyperinsulinism

In congenital hyperinsulinism (HI), the in vivo pancreatic β-cell function is poorly described. Among 14 neonates with severe hyperinsulinaemic hypoglycaemia, 2 patients had very prolonged or persistent hypoglycaemia and mutation in the sulphonylurea receptor SUR1 gene. Patient 1 had transient HI and was treated medically for 3.5 mo before clinical remission was seen. He had initially very high basal and stimulated C-peptide and insulin levels, followed by a state of normal preprandial values, but blunted β-cell glucose sensitivity, before complete β-cell normalization occurred. A single, paternal SUR1 mutation, G1382S, was found suggesting focal type HI. Patient 2 had persistent HI and underwent 3 pancreas resections up to the age of 2 y, 7 mo, followed by a state of mild diabetes. On biopsy, diffuse-type β-cell hypertrophy was seen. The β-cell response to glucose and glucagon stimulation was blunted before, as well as after, pancreas resections. Compound heterozygosity for the SUR1 mutations 3992–3c to g and N188S was found. Conclusion: Transient, possibly focal, HI with paternal SUR1 mutation was associated with a gradual, but complete normalization of the in vivoβ-cell function; in the diffuse type HI, a blunted β-cell response to glucose and glucagon stimulation persisted. In vivoβ-cell stimulation tests may contribute to the characterization of the HI subtypes.