A5060590046- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Food Allergy and Anaphylaxis Research
- Diabetes Treatment and Management
- Animal Disease Management and Epidemiology
- Drug-Induced Adverse Reactions
- COVID-19 Clinical Research Studies
- Sepsis Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Long-Term Effects of COVID-19
- Asthma and respiratory diseases
- Allergic Rhinitis and Sensitization
- Food Safety and Hygiene
Benaroya Research Institute
2020-2024
Virginia Mason Medical Center
2021-2024
Immune Tolerance Network
2019-2022
Seattle University
2022
BACKGROUNDResidual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, physiologic significance low levels detectable not known.METHODSWe studied 63 adults with diabetes classified by peak mixed-meal tolerance test (MMTT) as negative (<0.007 pmol/mL; n = 15), (0.017-0.200; 16), intermediate (>0.200-0.400; or high (>0.400; 17). We compared groups' glycemia from continuous glucose monitoring (CGM), β cell secretory responses a glucose-potentiated...
Abstract Context The value of continuous glucose monitoring (CGM) for autoantibody (AAB)-positive individuals in clinical trials progression type 1 diabetes (T1D) is unknown. Objective Compare CGM with oral tolerance test (OGTT)–based metrics prediction T1D. Methods At academic centers, OGTT and data from multiple-AAB relatives were evaluated associations T1D diagnosis. Participants multiple-AAB–positive a TrialNet Pathway to Prevention (TN01) ancillary study (n = 93). intervention was week...
CD4 + CD25 hi CD127 lo/− FOXP3 regulatory T cells (T regs ) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal has been shown to be safe adults phase clinical trials. We explored factors contributing efficacy expanded (expT randomized 2 multi-center, double-blind, trial (Sanford/Lisata Therapeutics T-Rex trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were...
The Learning Early About Peanut allergy (LEAP) study has shown the effectiveness of early peanut introduction in prevention (PA). In Enquiring Tolerance (EAT) study, a statistically significant reduction PA was present only per-protocol (PP) analyses, which can be subject to bias.The aim this combine individual-level data from LEAP and EAT trials provide robust evidence on bias-corrected, causal effect introduction.As part European Union-funded iFAAM project, pooled analysis individual...
Abstract Background Perioperative anaphylaxis (PA) in children is an uncommon but potentially life‐threatening complication associated with anesthesia. Early identification and management of PA essential to optimize clinical outcomes. Methods We performed a retrospective study anesthesia records from pediatric patients centers the United Kingdom, France, States over period 10 years. Time sequence signs physiological variables during were collected, along results allergy testing. Results...
Abstract Background Essentially all individuals with multiple autoantibodies will develop clinical type 1 diabetes. Multiple (AABs) and normal glucose tolerance define stage diabetes; abnormal defines 2. However, the rate of progression within these stages is heterogeneous, necessitating personalized risk calculators to improve implementation. Methods We developed 3 models using TrialNet's Pathway Prevention data accommodate reality that not variables are clinically available. The small...
Abstract Context There is an unmet need for biomarkers of pancreatic beta-cell death to improve early diagnosis type 1 diabetes, enroll subjects into clinical trials, and assess treatment response. To address this need, several groups developed assays measuring insulin deoxyribonucleic acid (DNA) with unmethylated CpG sites in cell-free DNA. Unmethylated DNA should be derived predominantly from beta-cells indicate ongoing death. Objective the performance three assays. Design Participants...
Exhausted CD8 T cells (T
Abstract The use of a standardized outcome metric enhances clinical trial interpretation and cross-trial comparison. If disease course is predictable, comparing modeled predictions with data affords the precision confidence needed to accelerate medicine. We demonstrate this approach in type 1 diabetes (T1D) trials aiming preserve endogenous insulin secretion measured by C-peptide. C-peptide predictable given an individual’s age baseline value; quantitative response (QR) adjusts for these...
The presence of islet autoimmunity identifies individuals likely to progress clinical type 1 diabetes (T1D). In research studies, autoantibody screening followed by regular metabolic monitoring every 6 months reduces incidence diabetic ketoacidosis (DKA) at diagnosis.
Comprehensive data on early prognostic indicators in patients with mild COVID-19 remains sparse. In this single center case series, we characterized the initial clinical presentation 180 and defined earliest predictors of subsequent deterioration need for hospitalization. Three broad patient phenotypes four symptom clusters were characterized, differentiated by varying risk adverse outcomes. Among 14 symptoms assessed, subjective shortness breath (SOB) most strongly associated outcomes (odds...
Abstract The use of a standardized outcome metric enhances clinical trial interpretation and cross-trial comparison. If disease course is predictable, comparing modeled predictions with data affords the precision confidence needed to accelerate medicine. We demonstrate this approach in type 1 diabetes (T1D) trials aiming preserve endogenous insulin secretion measured by C-peptide. C-peptide predictable given an individual’s age baseline value; quantitative response (QR) adjusts for these...
Abstract Exhausted CD8 T cells (TEX) are associated with worse outcome in cancer and better autoimmunity. However, factors contributing to reduced TEX the context of autoimmunity not well understood. Here, we identify co-expression TIGIT KLRG1 as a broad identifier human TEX: TIGIT+KLRG1+ memory share EOMES signature genes healthy controls (HC), T1D Rheumatoid Arthritis (RA) subjects, increased age chronic viral-specific cells, hyporesponsive (reduced proliferation cytokine production)...