The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

Abstract

Congenital hyperinsulinism (CHI) is the result of unregulated insulin secretion from the pancreatic β-cells leading to severe hypoglycaemia. In these patients it is important to make an accurate diagnosis and initiate the appropriate management so as to avoid hypoglycemic episodes and prevent the potentially associated complications like epilepsy, neurological impairment and cerebral palsy. At a genetic level abnormalities in eight different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and UCP2) have been reported with CHI. Loss of function mutations in ABCC8/KCNJ11 lead to the most severe forms of CHI which are usually medically unresponsive. At a histological level there are two major subgroups, diffuse and focal, each with a different genetic etiology. The focal form is sporadic in inheritance and is localized to a small region of the pancreas whereas the diffuse form is inherited in an autosomal recessive (or dominant) manner. Imaging using a specialized positron emission tomography scan with the isotope fluroine-18 L-3, 4-dihydroxyphenyalanine (18F-DOPA-PET-CT) is used to accurately locate the focal lesion pre-operatively and if removed can cure the patient from hypoglycemia. Understanding the molecular mechanisms, the histological basis, improvements in imaging modalities and surgical techniques have all improved the management of patients with CHI.

Ghrelin

“…ob/ob mice demonstrated that the ablation of ghrelin improves the diabetic phenotype with increased insulin secretion, reduced blood glucose and improved glucose tolerance (6). Mitochondrial uncoupling protein 2 (UCP2) decreases ATP production to lower the ATP:ADP ratio, a key signal needed for insulin secretion (25). The ghrelin −/− .…”

Hyperinsulinemic Hypoglycemia Syndrome in 2 Dogs with Bartonellosis

“…Hyperinsulinemic hypoglycemia syndrome (HHS) is considered the most common cause of persistent hypoglycemia in infants and children 3, 4. To the authors' knowledge, HHS has not been previously reported as a distinct clinical entity in dogs.…”

Current Status of Childhood Hyperinsulinemic Hypoglycemia in Turkey

“…The clinical presentation of HH can be very heterogeneous ranging from very subtle presentation to severe disease needing pancreatectomy (2,3,4,5). It can be either permanent or transient; the permanent form is usually known as congenital.…”