β-Cell Function and Glucose Tolerance in Persons With Multiple Islet Autoantibodies Randomized to a Gluten-free Diet.

Purpose: A randomized clinical trial was conducted to evaluate the impact of a gluten-free diet (GFD) on β-cell function and glucose tolerance in persons with multiple islet autoantibodies.

Methods: Individuals (n = 59; median age 11 years) with multiple islet autoantibodies were recruited to a randomized clinical trial between April 2016 and April 2021. The participants were randomized to a GFD (n = 30; female n = 14) or a normal diet (ND) (n = 29; female n = 16).

Insights into Knowledge and Attitudes About Autoantibody Screening from People Affected by Type 1 Diabetes: A Brief Report.

Introduction: Screening for islet-specific autoantibodies can identify individuals at risk for type 1 diabetes (T1D). Despite calls for increased nationwide autoantibody screening efforts, it is unclear how many individuals have participated in screening among people who may benefit from it. Moreover, knowledge and perceptions of autoantibody screening in real-world samples are not well understood.

Data-Driven Phenotyping of Presymptomatic Type 1 Diabetes Using Longitudinal Autoantibody Profiles.

Objective: To characterize distinct islet autoantibody profiles preceding stage 3 type 1 diabetes.

Research Design And Methods: The T1DI (Type 1 Diabetes Intelligence) study combined data from 1,845 genetically susceptible prospectively observed children who were positive for at least one islet autoantibody: insulin autoantibody (IAA), GAD antibody (GADA), or islet antigen 2 antibody (IA-2A). Using a novel similarity algorithm that considers an individual's temporal autoantibody profile, age at autoantibody appearance, and variation in the positivity of autoantibody types, we performed an unsupervised hierarchical clustering analysis.

Refining the Definition of Stage 1 Type 1 Diabetes: An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity.

Objective: To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA).

Research Design And Methods: Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S.

CGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study.

Objective: Continuous glucose monitoring (CGM) parameters may identify individuals at risk for progression to overt type 1 diabetes. We aimed to determine whether CGM metrics provide additional insights into progression to clinical stage 3 type 1 diabetes.

Research Design And Methods: One hundred five relatives of individuals in type 1 diabetes probands (median age 16.

Consortium-based approach to receiving an EMA qualification opinion on the use of islet autoantibodies as enrichment biomarkers in type 1 diabetes clinical studies.

The development of medical products that can delay or prevent progression to stage 3 type 1 diabetes faces many challenges. Of note, optimising patient selection for type 1 diabetes prevention clinical trials is hindered by significant patient heterogeneity and a lack of characterisation of the time-varying probability of progression to stage 3 type 1 diabetes in individuals positive for two or more islet autoantibodies. To meet these needs, the Critical Path Institute's Type 1 Diabetes Consortium was launched in 2017 as a pre-competitive public-private partnership between stakeholders from the pharmaceutical industry, patient advocacy groups, philanthropic organisations, clinical researchers, the National Institutes of Health and the Food and Drug Administration.

The Women's Leadership Gap in Diabetes: A Call for Equity and Excellence.

Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field.We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients.

Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories.

Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study.

Adult-Onset Type 1 Diabetes: Current Understanding and Challenges.

Recent epidemiological data have shown that more than half of all new cases of type 1 diabetes occur in adults. Key genetic, immune, and metabolic differences exist between adult- and childhood-onset type 1 diabetes, many of which are not well understood. A substantial risk of misclassification of diabetes type can result.

Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes: Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S.

Objective: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes.

Research Design And Methods: For prospective cohorts in Finland, Germany, Sweden, and the U.S.

The Women's Leadership Gap in Diabetes: A Call for Equity and Excellence.

Objective: Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field.

Research Design And Methods: We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients.

Neoepitopes in Type 1 Diabetes: Etiological Insights, Biomarkers and Therapeutic Targets.

The mechanisms underlying type 1 diabetes (T1D) pathogenesis remain largely unknown. While autoantibodies to pancreatic beta-cell antigens are often the first biological response and thereby a useful biomarker for identifying individuals in early stages of T1D, their role in T1D pathogenesis is not well understood. Recognition of these antigenic targets by autoreactive T-cells plays a pathological role in T1D development.

Predicting Type 1 Diabetes Onset using Novel Survival Analysis with Biomarker Ontology.

Type 1 diabetes (T1D) is a chronic autoimmune disease that affects about 1 in 300 children and up to 1 in 100 adults during their life-time. Improvements in early prediction of T1D onset may help prevent diagnosis for diabetic ketoacidosis, a serious complication often associated with a missed or delayed T1D diagnosis. In addition to genetic factors, progression to T1D is strongly associated with immunologic factors that can be measured during clinical visits.

Modeling Disease Progression Trajectories from Longitudinal Observational Data.

Analyzing disease progression patterns can provide useful insights into the disease processes of many chronic conditions. These analyses may help inform recruitment for prevention trials or the development and personalization of treatments for those affected. We learn disease progression patterns using Hidden Markov Models (HMM) and distill them into distinct trajectories using visualization methods.

A Triple Threat? The Role of Diet, Nutrition, and the Microbiota in T1D Pathogenesis.

In recent years the role of the intestinal microbiota in health and disease has come to the forefront of medical research. Alterations in the intestinal microbiota and several of its features have been linked to numerous diseases, including type 1 diabetes (T1D). To date, studies in animal models of T1D, as well as studies in human subjects, have linked several intestinal microbiota alterations with T1D pathogenesis.

Parent and Pediatrician Preferences for Type 1 Diabetes Screening in the U.S.

Objective: The purpose of this study was to use a discrete-choice experiment methodology to understand the relative importance of the attributes of screening tests for type 1 diabetes among parents and pediatricians in the U.S.

Research Design And Methods: Online surveys presented hypothetical screening test profiles from which respondents chose their preferred test profile.

Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes.

In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven.

JDRF's vision and strategy for prevention of type 1 diabetes.

The increasing incidence and lower threshold of developing type 1 diabetes (T1D) increases the urgency of its prevention. Insights from past and current natural history studies have provided the framework for a compelling strategy for primary and secondary prevention. Primary prevention of T1D should target the general childhood population with vaccines (viral or tolerogenic) or by altering microbiota-induced immunoregulation.

American Diabetes Association and JDRF Research Symposium: Diabetes and the Microbiome.

From 27-29 October 2014, more than 100 people gathered in Chicago, IL, to participate in a research symposium titled "Diabetes and the Microbiome," jointly sponsored by the American Diabetes Association and JDRF. The conference brought together international scholars and trainees from multiple disciplines, including microbiology, bioinformatics, endocrinology, metabolism, and immunology, to share the current understanding of host-microbe interactions and their influences on diabetes and metabolism. Notably, this gathering was the first to assemble specialists with distinct expertise in type 1 diabetes, type 2 diabetes, immunology, and microbiology with the goal of discussing and defining potential pathophysiologies linking the microbiome and diabetes.

Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association.

Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.