Background
Diabetes ketoacidosis (DKA) is a common presentation and complication of type 1 diabetes (T1D). While intravenous insulin is typically used to treat acute metabolic abnormalities, the ...transition from intravenous to subcutaneous treatment can present a challenge. We hypothesize that co‐administration of glargine, a subcutaneous long‐acting insulin analog, during insulin infusion may facilitate a flexible and safe transition from intravenous to subcutaneous therapy.
Objective
To determine if the practice of administering subcutaneous glargine during intravenous insulin is associated with an increased risk of hypoglycemia, hypokalemia, or other complications in children with DKA.
Methods
Retrospective chart review of patients aged 2 to 21 years, presenting to our center with DKA between April 2012 and June 2014. Patients were divided into two groups: those co‐administered subcutaneous glargine with intravenous insulin for over 4 hours (G+); and patients with less than 2 hours of overlap (G−).
Results
We reviewed 149 DKA admissions (55 G+, 94 G−) from 129 unique patients. There was a similar incidence of hypoglycemia between groups (25% G+ vs 20% G−, P = 0.46). Hypokalemia (<3.5 mmol/L) occurred more frequently in the G+ group (OR = 3.4, 95% CI 1.7‐7.0, P = 0.001). Cerebral edema occurred in 2/55 (3.6%) of the G− group and none of the G+ subjects.
Conclusion
Co‐administration of glargine early in the course of DKA treatment is well tolerated and convenient for discharge planning; however, this approach is associated with an increased risk of hypokalemia.
Congenital hyperinsulinism (HI) can have monogenic or syndromic causes. Although HI has long been recognised to be common in children with Beckwith-Wiedemann syndrome (BWS), the underlying mechanism ...is not known.
We characterised the clinical features of children with both HI and BWS/11p overgrowth spectrum, evaluated the contribution of KATP channel mutations to the molecular pathogenesis of their HI and assessed molecular pathogenesis associated with features of BWS.
We identified 28 children with HI and BWS/11p overgrowth from 1997 to 2014. Mosaic paternal uniparental isodisomy for chromosome 11p (pUPD11p) was noted in 26/28 cases. Most were refractory to diazoxide treatment and half required subtotal pancreatectomies. Patients displayed a wide range of clinical features from classical BWS to only mild hemihypertrophy (11p overgrowth spectrum). Four of the cases had a paternally transmitted KATP mutation and had a much more severe HI course than patients with pUPD11p alone.
We found that patients with pUPD11p-associated HI have a persistent and severe HI phenotype compared with transient hypoglycaemia of BWS/11p overgrowth patients caused by other aetiologies. Testing for pUPD11p should be considered in all patients with persistent congenital HI, especially for those without an identified HI gene mutation.
hyperinsulinism/hyperammonemia syndrome Palladino, Andrew A; Stanley, Charles A
Reviews in endocrine & metabolic disorders,
09/2010, Letnik:
11, Številka:
3
Journal Article
Recenzirano
The hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common form of congenital hyperinsulinism (HI). Children affected by this syndrome have both fasting and protein sensitive ...hypoglycemia combined with persistently elevated ammonia levels. Gain of function mutations in the mitochondrial enzyme glutamate dehydrogenase (GDH) are responsible for the HI/HA syndrome. GDH is expressed in liver, kidney, brain, and pancreatic beta-cells. Patients with the HI/HA syndrome have an increased frequency of generalized seizures, especially absence-type seizures, in the absence of hypoglycemia. The hypoglycemia of the HI/HA syndrome is well controlled with diazoxide, a KATP channel agonist. GDH has also been implicated in another form of HI, short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency associated HI. The HI/HA syndrome provides a rare example of an inborn error of intermediary metabolism in which the effect of the mutation on enzyme activity is a gain of function.
The daily injection burden of recombinant human growth hormone (r-hGH) replacement therapy to treat growth hormone deficiency (GHD) may reduce compliance and limit treatment benefit. Research is ...needed to evaluate patient preferences for GHD injection regimen and device features.
Quantitatively evaluate factors driving preferences for r-hGH injection regimen and device features among pediatric (3-17 years, and caregivers) and adult (≥25 years) patients with GHD using a discrete choice experiment (DCE) approach.
The DCE was part of a broader, cross-sectional observational field study to develop clinical outcome assessments (COAs) that assess the experience of patients taking r-hGH injections. Following ethics approval, discrete choice data were collected through an online questionnaire from consented participants recruited from eight sites in the United States. Participants were presented with 20 choice tasks, each comprising different combinations of two profiles. Participants were then shown the same set of three hypothetical device and injection profiles (ie, storage, preparation, injection type device, maintenance, dose setting, injection schedule) and asked whether they would choose each profile over their current device and schedule. Choice-based conjoint analyses were used to estimate the marginal utilities and values for treatment attributes. Subject preferences were estimated at individual and aggregate levels.
Two hundred and twenty-four participants completed the DCE (n=75 adults, n=79 adolescent/caregiver dyads, n=70 child/caregiver dyads). Injection schedule was the strongest predictor of choice for the total sample and each patient group. Less frequent injection schedules were more likely to be chosen by participants. A "ready to use" injection was preferred, with no preference for auto-injector versus needle-free device. Most participants would choose the hypothetical injection devices and less frequent dosing over their current daily administered device schedule.
Patients prefer a less frequent injection regimen for treating GHD. Addressing patient preferences may improve compliance, adherence, and ultimately, clinical outcomes.
Abstract Purpose The purpose of the study was to determine the sensitivity of the18 fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography scan (18 F-PET/CT) in the diagnosis ...of focal congenital hyperinsulinism (HI). Methods A retrospective review of children with HI who underwent a preoperative 18 F-PET/CT scan was performed. Results Between 1/2008 and 2/2012 we performed 105 consecutive 18 F-PET/CT scans on infants with HI. Fifty-three patients had focal HI. Of those fifty-three patients, eight had a preoperative 18 F-PET/CT scan read as “diffuse disease”. The sensitivity of the study in the diagnosis of focal HI was 85%. The location of the eight missed focal lesions was: head (3), body (2), and tail (3). The 18 F-PET/CT of the missed head lesions showed homogeneous tracer uptake (n = 2) or heterogeneous uptake throughout the pancreas (n = 1). The 18 F-PET/CT of the 2 missed body lesions and 1 missed tail lesion showed heterogeneous uptake throughout the pancreas. The 18 F-PET/CT of the other 2 missed tail lesions showed lesions adjacent to and obscured by the signal of the upper renal pole, identified retrospectively by closer observation. Fifty-two of the 105 patients had diffuse HI. Two of them had 18 F-PET/CT studies read as “focal disease”. Therefore, the specificity of the study was 96%. Of the forty-seven 18 F-PET/CT studies read as “focal disease”, forty-five had true focal HI. Therefore, the positive predictive value of the study in the diagnosis of focal HI was 96%. Conclusion The sensitivity and specificity of 18 F-PET/CT can be affected by certain anatomic features of the pancreas, by the location of the lesion, and by the reader's experience.
Abstract Purpose To determine the outcome of patients who underwent pancreatic head resection and Roux-en-Y pancreaticojejunostomy to the remaining normal pancreatic body and tail for the treatment ...of a focal lesion in the pancreatic head causing congenital hyperinsulinism (HI). Methods One hundred thirty-eight patients underwent pancreatic resection for focal HI between 1998 and 2010. Twenty-three patients in the group underwent pancreatic head resection and Roux-en-Y pancreaticojejunostomy. Results There were 13 females and 10 males. Median age and weight at surgery were 8 weeks and 5.8 kg, respectively. Twenty-one patients had a near-total pancreatic head resection, and 2 patients had a pylorus-preserving Whipple procedure. The pancreaticojejunostomy anastomosis was performed with interrupted fine monofilament sutures such that the transected end of the pancreatic body was tucked within the end of the Roux-en-Y jejunal limb. Median hospital stay was 22 days. All patients were cured of HI. Conclusion We conclude that pancreatic head resection with Roux-en-Y pancreaticojejunostomy is a safe and effective procedure for the treatment of the HI patient with a large focal lesion in the pancreatic head that is not amenable to local resection alone.
Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. In cases of diazoxide-unresponsive HI, alternative medical and surgical approaches may be ...required to reduce the risk of hypoglycemia. Octreotide, a somatostatin analog, often has a role in the management of these children, but a dose-dependent reduction in splanchnic blood flow is a recognized complication. Necrotizing enterocolitis (NEC) has been reported within the first few weeks of initiating predominantly high doses of octreotide. We describe the case of an infant with Beckwith-Wiedemann syndrome and diazoxide-unresponsive HI, who had persistent hypoglycemia after two pancreatectomy surgeries. She developed NEC 2 months after beginning octreotide therapy at a relatively low dose of 8 µg/kg/day. This complication has occurred later, and at a lower dose, than has previously been described. We review the case and identify the known and suspected multifactorial risk factors for NEC that may contribute to the development of this complication in patients with HI.
Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD).
Taliglucerase Alfa ...Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019.
A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients.
The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.
Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of ...hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders.
Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1. Hyperinsulinism can be associated with perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia. Mimickers of hyperinsulinism include neonatal panhypopituitarism, drug-induced hypoglycemia, insulinoma, antiinsulin and insulin-receptor stimulating antibodies, Beckwith-Wiedemann Syndrome, and congenital disorders of glycosylation. Laboratory testing for hyperinsulinism may include quantification of blood glucose, plasma insulin, plasma beta-hydroxybutyrate, plasma fatty acids, plasma ammonia, plasma acylcarnitine profile, and urine organic acids. Genetic testing is available through commercial laboratories for genes known to be associated with hyperinsulinism. Acute insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying hyperinsulinism. The goal of treatment in infants with hyperinsulinism is to prevent brain damage from hypoglycemia by maintaining plasma glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical therapy.
The management of hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating hyperinsulinism.
Hyperinsulinism (HI) is the most common cause of transient and permanent forms of hypoglycemia in infancy. Establishing the correct diagnosis and initiating appropriate therapy without delay is of ...utmost importance. Once the diagnosis is made and if medical therapy with diazoxide fails, one should assume that the infant has a KATP channel defect and may require surgery. In this case, the infant should be referred to a center that specializes in HI with 18-fluoro L-3,4-dihydroxyphenylalanine positron emission tomography scan. This report describes a center specializing in HI with a team of experts consisting of endocrinologists, nurse practitioners, geneticists, radiologists, pathologists, and a surgeon. It describes the center's paradigm for managing severe HI on the basis of more than 250 cases of HI in the past 10 years, including the diagnosis of HI, medical options, genetics of HI, imaging in HI, the surgical approach to HI, and outcomes.
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