Management Of Congenital Hyperinsulinism Research Articles

Families' Experiences of Continuous Glucose Monitoring in the Management of Congenital Hyperinsulinism: A Thematic Analysis.

Background and AimsIn patients with congenital hyperinsulinism (CHI), recurrent hypoglycaemia can lead to longstanding neurological impairments. At present, glycaemic monitoring is with intermittent fingerprick blood glucose testing but this lacks utility to identify patterns and misses hypoglycaemic episodes between tests. Although continuous glucose monitoring (CGM) is well established in type 1 diabetes, its use has only been described in small studies in patients with CHI. In such studies, medical perspectives have been provided without fully considering the views of families using CGM. In this qualitative study, we aimed to explore families’ experiences of using CGM in order to inform future clinical strategies for the management of CHI.MethodsTen patients with CHI in a specialist centre used CGM for twelve weeks. All were invited to participate. Semi-structured interviews were conducted with nine families in whom patient ages ranged between two and seventeen years. Transcripts of the audio-recorded interviews were analysed using an inductive thematic analysis method.ResultsAnalysis revealed five core themes: CGM’s function as an educational tool; behavioural changes; positive experiences; negative experiences; and design improvements. Close monitoring and retrospective analysis of glucose trends allowed for enhanced understanding of factors that influenced glucose levels at various times of the day. Parents noted more hypoglycaemic episodes than previously encountered through fingerprick tests; this new knowledge prompted modification of daily routines to prevent and improve the management of hypoglycaemia. CGM use was viewed favourably as offering parental reassurance, reduced fingerprick tests and predictive warnings. However, families also reported unfavourable aspects of alarms and questionable accuracy at low glucose levels. Adolescents were frustrated by the short proximity range for data transmission resulting in the need to always carry a separate receiver. Overall, families were positive about the use of CGM but expected application to be tailored to their child’s medical condition.ConclusionsPatients and families with CHI using CGM noticed trends in glucose levels which motivated behavioural changes to reduce hypoglycaemia with advantages outweighing disadvantages. They expected CHI-specific modifications to enhance utility. Future design of CGM should incorporate end users’ opinions and experiences for optimal glycaemic monitoring of CHI.

Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia

New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide. Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.

Investigation and management of acute hypoglycemia

Since prolonged severe hypoglycemia could lead to permanent neurological sequelae, it must be treated immediately. But at the same time, the cause of hypoglycemia should be determined to prevent future recurrence of hypoglycemia preferably at bedside while the patient is still in an emergency room. Most of the cases, this could be done by asking proper questions and taking physical findings in parallel with the treatment, without waiting for the detailed results of critical samples. In taking history of the patients, one should not forget to ask the following questions; (1) preexisting medical problems (especially diabetes mellitus, CNS tumors, adrenal insufficiency, hepatic failure, arrhythmia, citrin deficiency or chronic infections), (2) medication history (especially insulin, oral hypoglycemic agents, beta-blocker, disopyramide, or extended use of antibiotics containing pivalic acid), (3) timing of hypoglycemia following the last meal (VERY important). In taking physical findings, presence or absence of hepatomegaly and circulatory collapse is the most important. Hypoglycemia within 2-3 hours after meal almost invariably suggests the presence of hyperinsulinemia. Hypoglycemia caused by a defect in glycogenolysis typically occurs 5-8 hours following the last meal and is usually accompanied by hepatomegaly. Recurrent episodes of hypoglycemia after an overnight fast likely suggest a problem in gluconeogenesis. Circulatory collapse at hypoglycemia suggests the presence of adrenal insufficiency. IV steroid in addition to IV glucose should be considered to prevent neurological sequelae. Critical samples should be taken at the time of hypoglycemia to make a causal diagnosis. Although the turnaround time of endocrine tests or tandem mass-spectrometry is usually long, results available on site often give a clue to the diagnosis. Relatively low ketone bodies by urine dipsticks suggest the presence of hyperinsulinemia or rare disorders of fatty-acid oxidation defects. Hyponatremia accompanied by hyperkalemia suggests primary (not secondary) adrenal insufficiency. Response to initial therapy also gives an important clue to the diagnosis. The need to continue IV glucose over normal resting hepatic glucose production to maintain normoglycemia (4-6 mg/kg.min in neonates) strongly suggests the presence of hyperinsulinemia. Never infuse too much glucose to the patients which could obscure the diagnosis. Finally, I will spend some time to show current state-of-the art in the diagnosis and management of congenital hyperinsulinism and discuss how the patients should be managed in the Asia-Pacific region.

Surgical Management of Congenital Hyperinsulinism in a Resource-Limited Setting

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The molecular mechanisms, diagnosis and management of congenital hyperinsulinism

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.

Investigation and management of congenital hyperinsulinism

Insulin is a powerful hormone produced by the beta-cells in the pancreas. Its major function is to regulate blood glucose levels, facilitating the transport of glucose into the body's cells. Congenital hyperinsulinism is characterized by the presence of insulin that is inappropriately high for the concentration of blood glucose. Because high levels of insulin also switch off all alternative fuels for the brain to use, this condition can cause brain injury if not detected quickly. Nurses are in a unique position by the bedside to identify the symptoms and treat the hypoglycaemia through very simple nursing interventions, such as safe administration of glucose and frequent blood glucose monitoring. Congenital hyperinsulinism can be transient or persistent. Persistent congenital hyperinsulinism can be further divided into focal or diffuse disease. Focal congenital hyperinsulinism can now be cured, and the management of congenital hyperinsulinism has radically changed with the help of genetics and research. Now pancreatectomy surgery is only used as the last resort.

PET scan in management of congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a cause of severe hypoglycemia in the neonates. The pancreatic involvement can be diffuse or focal. The preoperative differentiation of these two forms is very important because the surgical management is radically different. The focal form of the disease can be cured if the focal lesion can be localized accurately and resected completely. In recent years, considerable progress has been made in the biochemical, morphological and molecular genetic differentiation of CHI. Fluorine-18 L-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET) has been introduced for differentiation between focal and diffuse CHI. The ability to take up L-DOPA and convert it into dopamine is correlated with the activity of the aromatic amino acid decarboxylase and is increased in the hyper functional pancreatic area in comparison to normally functioning pancreas. The high sensitivity of this method allows the surgeon to perform appropriate resection of a focus without the risk of long-term diabetes. Patients with CHI should be managed within a strong network of diagnostic, treatment, and research institutions.

Conservative management of congenital hyperinsulinism shows good neurological outcomes

Conservative management of congenital hyperinsulinism shows good neurological outcomes

Diagnosis and management of congenital hyperinsulinism: a case report

Congenital hyperinsulinism (CHI) is a common cause of persistent hypoglycaemia in neonates, with an estimated incidence of one in 50 000 live births (1). The molecular basis for CHI can be established in approximately 50% of the cases and is categorised as channelopathies – defects in the ATP-sensitive potassium (KATP) channels that regulate insulin secretion, and metabolopathies – defects in metabolic pathways altering b-cell function (2). Channelopathies form the largest group and can be further sub-divided into focal and diffuse forms. In contrast to metabolopathies, most channelopathies do not respond to pharmacological treatment and require surgical removal of either focal lesions or, in diffuse forms, near total (O97%) pancreatectomy. This case report describes the diagnostic and therapeutic challenges in a patient with CHI. More extensive background information on CHI can be found elsewhere (2).