Study Objectives: The prevalence of obstructive sleep apnea (OSA) increases dramatically in adolescents with overweight or obesity. The gold standard for diagnosis of OSA is in-laboratory polysomnography (PSG). However, access to PSG can be challenging, necessitating development of alternative devices.
View Article and Find Full Text PDFSexual dimorphism plays an important role in the pathogenesis and progression of CKD. Men with CKD often exhibit faster kidney function decline, leading to higher rates of kidney failure and mortality compared with women. Studies suggest that sex hormones may influence this apparent dimorphism, although the mechanisms underlying these influences remain poorly understood.
View Article and Find Full Text PDFObjectives: To measure physical activity in a cohort of children who survived greater than or equal to 3 days of invasive ventilation.
Design: Prospective cohort study (2018-2021).
Setting: Quaternary children's hospital PICU.
Purpose: MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant.
View Article and Find Full Text PDFIntroduction: Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable, and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease.
View Article and Find Full Text PDFBACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.
View Article and Find Full Text PDFKey Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.
View Article and Find Full Text PDFBackground: Chronic kidney disease (CKD) affects over 10 % of the global population and can lead to kidney failure and death. Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with increased risk of CKD, yet studies examining the mechanisms linking PFAS and kidney function are lacking. In this exploratory study, we examined longitudinal associations of PFAS exposure with kidney function, and tested if associations were mediated by altered gut bacterial taxa or plasma metabolites using a multi-omics mediation analysis.
View Article and Find Full Text PDFLocal adaptation may facilitate range expansion during invasions, but the mechanisms promoting destructive invasions remain unclear. Cheatgrass (), native to Eurasia and Africa, has invaded globally, with particularly severe impacts in western North America. We sequenced 307 genotypes and conducted controlled experiments.
View Article and Find Full Text PDFBackground: Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition.
Objective: This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia.
One of the challenges in studying islet inflammation-insulitis-is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinder intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet.
View Article and Find Full Text PDFObjective: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes.
Research Design And Methods: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10-17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention.
Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive.
Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis.
Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390).
Context: Small cohorts of youth with congenital adrenal hyperplasia (CAH) demonstrate increased risk of obesity and poor cardiometabolic health.
Objective: To determine the odds of cardiometabolic-related diagnoses in youth with CAH compared to matched controls in a cross-sectional analysis in a large, multisite database (PEDSnet).
Design: Electronic health record data (2009-2019) were used to determine odds of cardiometabolic-related outcomes based on diagnosis, anthropometric and laboratory data using logistic regression among youth with CAH vs.
One of the challenges in studying islet inflammation - insulitis - is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinders intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet.
View Article and Find Full Text PDFBackground And Objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations.
Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites.
Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden.
Study Design: Cross-sectional study.
Setting & Participants: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.
Background: Elevated depression symptoms have been associated with higher insulin resistance in adolescents, and consequently, greater risk for type 2 diabetes (T2D). Mindfulness-based intervention (MBI) may be suited for adolescents at risk for T2D given its potential to decrease depression and improve stress-related behavior/physiology underpinning insulin resistance. To prepare for a future multisite efficacy randomized controlled trial, a rigorous, multisite, pilot and feasibility study is needed to test this approach.
View Article and Find Full Text PDFContext: In Colorado children, the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes has been increasing over time.
Objective: To evaluate the prevalence of and factors involved in DKA at type 1 diabetes diagnosis among participants followed in monitoring research studies before diagnosis compared to patients from the community.
Methods: We studied patients < 18 years diagnosed with type 1 diabetes between 2005 and 2021 at the Barbara Davis Center for Diabetes and compared the prevalence of and factors associated with DKA at diagnosis among participants in preclinical monitoring studies vs those diagnosed in the community.
Continuous glucose monitoring (CGM) devices are integral in the outpatient care of people with type 1 diabetes, although they lack inpatient labeling. Food and Drug Administration began allowing inpatient use during the coronavirus disease 2019 (COVID-19) pandemic, with some accuracy data now available, primarily from adult hospitals. Pediatric inpatient data remain limited, particularly during diabetic ketoacidosis (DKA) admissions and for patients receiving intravenous (IV) insulin.
View Article and Find Full Text PDFObjective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, insulin resistance, and hepatic steatosis (HS). Because dietary essential amino acid (EAA) supplementation has been shown to decrease HS in various populations, this study's objective was to determine whether supplementation would decrease HS in PCOS.
Methods: A randomized, double-blind, crossover, placebo-controlled trial was conducted in 21 adolescents with PCOS (BMI 37.