Treatment Of Hyperinsulinemic Hypoglycemia Research Articles

Genetic Variations in Hyperinsulinemic Hypoglycemia: Active versus Inactive Mutations.

Hyperinsulinemic Hypoglycemia (HH) is a rare condition that affects newborn children in the postnatal period, represented by dangerously low levels of blood glucose in a persistent manner, which puts the baby at high risk of multiple issues, especially regarding the brain cells if the baby does not take the appropriate medication or have the correct diagnosis. Hyperinsulinemic Hypoglycemia can happen due to an active or inactive mutation in 16 genes responsible for glucose metabolism and insulin secretion (GLUD1, GCK, SLC16A1, HK1, CACNA1D, KCNJ11, ABCC8, FOXA2, HNF1A, HNF4A, HADH, PGM1, UCP2, KCNQ1, PMM2, EIF2S3). These mutations can take place in many forms, either defused or local, affecting several or all pancreatic beta cells respectively. This review summarizes genetic variations diagnosis and treatment of Hyperinsulinemic Hypoglycemia.

Diazoxide for Neonatal Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension.

Hypoglycemia in neonates is associated with long-term neurodevelopmental effects. Hyperinsulinemic hypoglycemia (HH) is the most common cause of persistent hypoglycemia in neonatal intensive care units. Diazoxide is the only medication that is currently recommended for treatment of HH in neonates. However, the use of diazoxide in neonates is associated with pulmonary hypertension as an adverse effect. In this article, we review the literature on the mechanism of action and adverse effects with the use of diazoxide in neonatal hyperinsulinism. We then present a case series of neonates treated with diazoxide in our neonatal intensive care unit over a 5-year period. Among 23 neonates who received diazoxide, 4 developed pulmonary hypertension and 1 died. All infants who developed pulmonary hypertension were born preterm at less than 36 weeks gestation and had pre-existing risk factors for pulmonary hypertension. HH in preterm neonates, with pre-existing pulmonary hypertension or with risk factors for pulmonary hypertension requires thoughtful management.

Receptor-Targeted Photodynamic Therapy of Glucagon-Like Peptide 1 Receptor-Positive Lesions.

Treatment of hyperinsulinemic hypoglycemia is challenging. Surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism is invasive and carries major risks of morbidity. Medication to treat nesidioblastosis and diffuse congenital hyperinsulinism has varying efficacy and causes significant side effects. Here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing β-cells by receptor-targeted photodynamic therapy (rtPDT) with exendin-4-IRDye700DX, targeting the glucagon-like peptide 1 receptor (GLP-1R). Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. The efficacy and specificity of rtPDT with exendin-4-IRDye700DX were examined in vitro in cells with different levels of GLP-1R expression. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. Induction of cellular damage and the effect on tumor growth were analyzed to determine treatment efficacy. Results: Exendin-4-IRDye700DX has a high affinity for the GLP-1R, with a half-maximal inhibitory concentration of 6.3 nM. rtPDT caused significant specific phototoxicity in GLP-1R–positive cells (2.3% ± 0.8% and 2.7% ± 0.3% remaining cell viability in CHL-GLP-1R and INS-1 cells, respectively). The tracer accumulates dose-dependently in GLP-1R–positive tumors. In vivo, rtPDT induces cellular damage in tumors, shown by strong expression of cleaved caspase-3, and leads to a prolonged median survival of the mice (36.5 vs. 22.5 d, respectively; P < 0.05). Conclusion: These data show in vitro as well as in vivo evidence of the potency of rtPDT using exendin-4-IRDye700DX. This approach might in the future provide a new, minimally invasive, highly specific treatment method for hyperinsulinemic hypoglycemia.

A novel treatment of hyperinsulinemic hypoglycemia induced by insulin antibodies with alkali administration: a case report

BackgroundInsulin autoimmune syndrome is a rare cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to human insulin without previous insulin use. We report a case of a patient with hyperinsulinemic hypoglycemia possibly caused by insulin antibodies induced by insulin analogs and a novel therapeutic measure for this condition.Case presentationAn 84-year-old Japanese man with a 28-year history of type 2 diabetes and chronic kidney disease, treated with biphasic insulin aspart 30, experienced persistent early morning hypoglycemia with daytime hyperglycemia. Despite discontinuation of biphasic insulin aspart 30, the condition persisted even after the patient ate small, frequent meals. Sodium bicarbonate was administered to correct the chronic metabolic acidosis, which then rectified the early morning glucose level.ConclusionsWe believe this to be the first published case of a therapeutic approach to the treatment of hyperinsulinemic hypoglycemia associated with insulin antibodies that factors in blood pH and the correction of acidosis using sodium bicarbonate, which physicians could consider.

PROPOSAL OF A REVISIONAL SURGERY TO TREAT NON-INSULINOMA HYPERINSULINEMIC HYPOGLICEMIA POSTGASTRIC BYPASS.

Background : Hyperinsulinemic hypoglicemia with severe neuroglycopenic symptoms has been identified as a late and rare complication in patients submitted to Roux-en-Y gastric bypass. However, the potential gravity of its manifestations requires effective treatment of this condition. The absence of treatment makes it necessary to develop more effective clinical or surgical methods. Aim : To present one surgical option to revisional surgery in the treatment of hyperinsulinemic hypoglicemia Methods : The procedure consists in reconstituting alimentary transit through the duodenum and proximal jejunum, while keeping the restrictive part of the gastric bypass. As an additional strategy to maintain weight loss, is realized gastric fundus resection, aiming to suppress ghrelin production more effectively. Results : It was used in three patients with successful results in one year of follow-up. Conclusion : The procedure to reconstruct the food transit through the duodenum and proximal jejunum, keeping the restrictive component of gastric bypass in the treatment of hyperinsulinemic hypoglycemia showed good initial results and validated its application in other cases with this indication.

Evaluation, Medical Therapy, and Course of Adult Persistent Hyperinsulinemic Hypoglycemia After Roux-En-Y Gastric Bypass Surgery: A Case Series

To describe the evaluation and treatment of hyperinsulinemic hypoglycemia in adults who had undergone gastric bypass surgery. A small number of patients who undergo Roux-en-Y bypass surgery develop postprandial hypoglycemia in the absence of dumping. In some cases, such patients have been treated with pancreatectomy. We report the demographics, diagnostic results, response to medical therapy, and subsequent course of 6 referral patients with post-Roux-en-Y gastric bypass hypoglycemia. Characteristic clinical and metabolic parameters consistent with hyperinsulinemic hypoglycemia were identified. Parameters were similar for both spontaneous and glucose-challenge-induced hypoglycemia. In the context of exclusively postprandial symptoms, simultaneous glucose ≤55 mg/dL, insulin ≥17 μU/mL, C peptide ≥3.0 ng/mL, and insulin to glucose ratio >0.3 were associated with Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia. Five of 6 patients improved on therapy consisting of dietary modification plus either calcium channel blockade, acarbose, or both. Two patients have remained on therapy for 12 to 15 months. The nonresponder was atypical and had had hypoglycemic events for several decades. Three treated patients were subsequently observed to have undergone partial or complete remission from hypoglycemic episodes after 2 to 37 months of therapy. None of the 6 have undergone pancreatectomy, and none have evidence of insulinoma. Invasive diagnostic procedures were of limited utility. In a subset of patients with post-Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia, medical management can be efficacious and an alternative to partial pancreatectomy. In some cases, the disorder remits spontaneously.

A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant.

Hyperinsulinemic hypoglycemia (HH) is the commonest cause of persistent hypoglycemia in the neonatal and infancy periods. Mutations in the ABCC8 and KCNJ11 genes, which encode subunits of the ATP-sensitive potassium channel in the pancreatic beta cell, are identified in approximately 50% of these patients. The first-line drug in the treatment of HH is diazoxide. Octreotide and glucagon can be used in patients who show no response to diazoxide. Nifedipine, a calcium-channel blocker, has been shown to be an effective treatment in a small number of patients with diazoxide-unresponsive HH. We report a HH patient with a homozygous ABCC8 mutation (p.W1339X) who underwent a near-total pancreatectomy at 2 months of age due to a lack of response to diazoxide and octreotide treatment. Severe hypoglycemic attacks continued following surgery, while the patient was being treated with octreotide. These attacks resolved when nifedipine was introduced. Whilst our patient responded well to nifedipine, the dosage could not be increased to 0.75 mg/kg/day due to development of hypotension, a reported side effect of this drug. Currently, our patient, now aged 4 years, is receiving a combination of nifedipine and octreotide treatment. He is under good control and shows no side effects. In conclusion, nifedipine treatment can be started in patients with HH who show a poor response to diazoxide and octreotide treatment.

Sirolimus Therapy in Infants with Severe Hyperinsulinemic Hypoglycemia

Hyperinsulinemic hypoglycemia is the most common cause of severe, persistent neonatal hypoglycemia. The treatment of hyperinsulinemic hypoglycemia that is unresponsive to diazoxide is subtotal pancreatectomy. We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 μg per kilogram per day). All the patients had a clear glycemic response to sirolimus, although one patient required a small dose of octreotide to maintain normoglycemia. There were no major adverse events during 1 year of follow-up.