Understanding and preventing type 1 diabetes through the unique working model of TrialNet

Abstract

Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.

Cell type–specific immune phenotypes predict loss of insulin secretion in new-onset type 1 diabetes

“…Because our data were limited to the immediate period after diagnosis, we cannot determine whether this pattern holds before diagnosis or into long-standing T1D. Longitudinal studies of insulin secretion are ongoing in TrialNet (42,43); defining the temporal loss of β cell function in T1D, from events prior to seroconversion through and beyond clinical diagnosis, will help to illuminate the triggers and immunological drivers of β cell damage in the early stages of T1D.…”

ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents

“…Because those with multiple antibodies will eventually develop clinical disease, intervention can be considered treatment of early type 1 diabetes, as distinct from prevention. Many consider that intervention at this stage will require combination approaches to multiple targets in the pathogenesis of type 1 diabetes: islet inflammation and autoimmune destruction, β‐cell function, and metabolism. Type 1 Diabetes TrialNet provides an international network of intervention trials to preserve β‐cell function at the different stages . The TrialNet Pathway to Prevention study screens and follows relatives of type 1 diabetes probands.…”

Relative Pancreas Volume Is Reduced in First-Degree Relatives of Patients With Type 1 Diabetes

“…Type 1 diabetes diagnosis was assigned according to American Diabetes Association criteria to patients who were within 1 year of onset (23). The FDR subjects were recruited within the National Institutes of Health (NIH) TrialNet network and were categorized by AAB status (negative, a single AAB, or multiple AABs) (24). Subjects with a history of exocrine insufficiency or pancreatitis were excluded.…”