A post-translational cysteine-to-serine conversion in human and mouse insulin generates a diabetogenic neoepitope.

Type 1 diabetes (T1D) affects a genetically susceptible population that develops autoreactive T cells attacking insulin-producing pancreatic β cells. Increasingly, neoantigens are recognized as critical drivers of this autoimmune response. Here, we report a novel insulin neoepitope generated via post-translational cysteine-to-serine conversion (C>S) in human patients, which is also seen in the autoimmune-prone non-obese diabetic (NOD) mice.

Hyperglycemia selectively increases cerebral non-oxidative glucose consumption without affecting blood flow.

Multiple studies have shown that hyperglycemia increases the cerebral metabolic rate of glucose (CMRglc) in subcortical white matter. This observation remains unexplained. Using positron emission tomography (PET) and euinsulinaemic glucose clamps, we found, for the first time, that acute hyperglycemia increases non-oxidative CMRglc (i.

F-DOPA PET/MRI With Carbidopa for the Diagnosis of Hyperinsulinemic Hypoglycemia in an Adolescent Patient.

Hyperinsulinism due to focal or diffuse pancreatic lesions causing recurrent episodes of hypoglycemia is rare in mid-childhood. There is no consensus on the gold-standard imaging method to diagnose focal insulin-producing lesions beyond infancy. A 14-year-old boy with a complex medical history and refractory epilepsy, presented with blood glucose (BG) of 52 mg/dL (2.

Mapping brain function in adults and young children during naturalistic viewing with high-density diffuse optical tomography.

Human studies of early brain development have been limited by extant neuroimaging methods. MRI scanners present logistical challenges for imaging young children, while alternative modalities like functional near-infrared spectroscopy have traditionally been limited by image quality due to sparse sampling. In addition, conventional tasks for brain mapping elicit low task engagement, high head motion, and considerable participant attrition in pediatric populations.

Pediatric diabetes mellitus hospitalizations and COVID-19 pandemic response measures.

Aims: In the United States, evidence suggests that during the COVID-19 pandemic, admissions of patients with diabetes mellitus (DM) have increased. This study assessed hospital admission rates for pediatric type 1 (T1DM) and type 2 (T2DM) diabetes mellitus during 2019-2021, and the potential influence of the timing of various pandemic response measures.

Methods: Retrospective chart reviews were conducted of 854 T1DM and 135 T2DM hospital admissions between January 2019 and December 2021 in patients < 20 years old to collect demographic data, admission type, body mass index (BMI), and area deprivation index (ADI, a measure of socioeconomic vulnerability).

Peak Serum Cortisol Cutoffs to Diagnose Adrenal Insufficiency Across Different Cortisol Assays in Children.

Objective: Current peak serum cortisol cutoffs for the diagnosis of adrenal insufficiency (AI) after Cosyntropin stimulation have been established using polyclonal antibody (pAb) immunoassays. However, new and highly specific cortisol monoclonal antibody (mAb) immunoassays are being used more widely, which can potentially yield higher false positive rates. Thus, this study aimed to redefine the biochemical diagnostic cutoff points for AI in children when using a highly specific cortisol mAb immunoassay and liquid chromatography tandem mass spectrometry (LC/MS) to avoid unnecessary steroid use.

Steroid Use in the NICU: Treatment and Tapering.

The adrenal gland cortex produces life-sustaining steroid hormones that are critical for the development and survival of the fetus and neonate. Antenatal and postnatal administration of steroids has critical therapeutic effects in preterm infants. However, prolonged postnatal steroid therapy for more than 1 to 2 weeks is associated with iatrogenic adrenal insufficiency and should prompt consideration of a steroid taper and stress dose precautions.

The impact of elexacaftor/tezacaftor/ivacaftor on body composition in a small cohort of youth with cystic fibrosis.

Background: The effects of elexacaftor-tezacaftor-ivacaftor (ETI) on body composition in people with CF (pwCF) are unknown.

Methods: Dual-energy X-ray absorptiometry fat-free mass and fat mass adjusted for height (FMI) as well as oral glucose tolerance test derived measures of insulin secretion and sensitivity were compared before and after ETI initiation in eight pwCF.

Results: Patients median age: 22 years interquartile range (IQR: 16-28), 87.

Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis.

Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.

Testing an Automated Approach to Identify Variation in Outcomes among Children with Type 1 Diabetes across Multiple Sites.

Introduction: Efficient methods to obtain and benchmark national data are needed to improve comparative quality assessment for children with type 1 diabetes (T1D). PCORnet is a network of clinical data research networks whose infrastructure includes standardization to a Common Data Model (CDM) incorporating electronic health record (EHR)-derived data across multiple clinical institutions. The study aimed to determine the feasibility of the automated use of EHR data to assess comparative quality for T1D.

A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes.

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system.

Association between Endocrine Disorders and Severe COVID-19 Disease in Pediatric Patients.

Introduction: Though severe illness due to COVID-19 is uncommon in children, there is an urgent need to better determine the risk factors for disease severity in youth. This study aims to determine the impact a preexisting endocrine diagnosis has on severity of COVID-19 presentation in youth.

Methods: The cross-sectional chart review study included all patients less than 25 years old with a positive SARS-CoV-2 PCR at St.

Comparison of Bioelectrical Impedance Analysis with DXA in Adolescents with Cystic Fibrosis before and after a Resistance Training Intervention.

Background: The purpose of this pilot study was to compare body composition metrics obtained by two portable bioelectrical impedance analysis (BIA) devices with dual-energy X-ray absorptiometry (DXA) among adolescents with cystic fibrosis (CF) before and after a resistance exercise training program.

Methods: Participants with CF were assessed using DXA, single-frequency BIA (SFBIA), and multiple-frequency BIA (MFBIA) to quantify percent body fat (%Fat), fat mass (FM), and fat-free mass (FFM) at baseline and after a home-based resistance training intervention comprised of 36, 1 h sessions completed in 12-14 weeks. Repeated measures analysis of variance, paired samples -tests, Cohen's d effect sizes, and Pearson's correlations were used to compare differences between and within methods at baseline and post-intervention.

Feasibility and Efficacy of Telehealth-Based Resistance Exercise Training in Adolescents with Cystic Fibrosis and Glucose Intolerance.

The aims of this study were to (1) determine the feasibility of a home-based resistance exercise training (RET) program in patients with cystic fibrosis and impaired glucose tolerance using virtual personal training and (2) observe the effects completion of the RET program had on glucose metabolism, pulmonary function, body composition, and physical fitness. The feasibility of the program was defined as 80% compliance. Ten participants (15.

Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay.

Objectives: The diagnosis of adrenal insufficiency relies on clear cut-offs and accurate measurement of cortisol levels. Newer monoclonal antibody assays may increase the rate of diagnosis of adrenal insufficiency if traditional cortisol cut-off levels <18 mcg/dL (500 nmol/L) are applied. We aimed to determine if the rate of diagnosis of adrenal insufficiency using a 1 mcg Cosyntropin stimulation test varied with the change in cortisol assay from a polyclonal to a monoclonal antibody assay.

The association between body composition, leptin levels and glucose dysregulation in youth with cystic fibrosis.

Background: Optimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls.

Vitamin B deficiency with normal plasma levels of pyridoxal 5'-phosphate in perinatal hypophosphatasia.

Pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B (B), is elevated in the plasma of individuals with hypophosphatasia (HPP). HPP is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). PLP accumulates extracellularly in HPP because it is a natural substrate of this cell-surface phosphomonoester phosphohydrolase.

Blood leukocytes recapitulate diabetogenic peptide-MHC-II complexes displayed in the pancreatic islets.

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells.

Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study.

Objective: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia.

Research Design And Methods: One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.

Portable, field-based neuroimaging using high-density diffuse optical tomography.

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays.

Executive task-based brain function in children with type 1 diabetes: An observational study.

Background: Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.

Methods And Findings: Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.

Inherited Deletion of 1q, Hyperparathyroidism and Signs of Y-chromosomal Influence in a Patient with Turner Syndrome.

We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS clinical characteristics including webbed neck, high arched palate and coarctation of the aorta, the patient had features less frequently seen in TS. These included recurrent parathyroid adenomas, growth along the 75-90 centiles on the TS height curve despite minimal treatment with growth hormone, behavioral problems and evidence of gonadal dysgenesis with testicular-like structures, such as seminiferous tubules lined by Sertoli cells and a contiguous nodule of Leydig cells.

Persistence of abnormalities in white matter in children with type 1 diabetes.

Aims/hypothesis: Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes.

Methods: One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres.

Quantitative positron emission tomography reveals regional differences in aerobic glycolysis within the human brain.

Glucose and oxygen metabolism are tightly coupled in the human brain, with the preponderance of the brain's glucose supply used to generate ATP via oxidative phosphorylation. A fraction of glucose is consumed outside of oxidative phosphorylation despite the presence of sufficient oxygen to do so. We refer to this process as aerobic glycolysis.