A new classification approach for the preclinical staging of type 1 diabetes has been developed by the Juvenile Diabetes Research Foundation (JDRF) and the American Diabetes Association (ADA).
The model, based on the concept that there is a progressive process leading up to symptomatic type 1 diabetes, "will aid the development of therapies and the design of clinical trials to prevent symptomatic disease and promote precision medicine," according to a joint JDRF/ADA statement published in the October issue of Diabetes Care.
While JDRF and ADA are not advising clinical use of the model for screening at this time, "the staging approach will provide a framework to help inform benefit/risk evaluation in the regulatory, reimbursement, and clinical-care settings," JDRF chief scientific officer Richard A Insel, MD, and colleagues write in the paper.
The three stages are:
Stage 1: Autoimmunity/normoglycemia/presymptomatic type 1 diabetes.Individuals in this stage have two or more type 1 diabetes–associated islet autoantibodies but are still normoglycemic. In one study of children who reached this stage, the risks for developing symptomatic disease were 44% at 5 years and 70% at 10 years, with a lifetime risk of nearly 100%.
Stage 2: Autoimmunity/dysglycemia/presymptomatic type 1 diabetes.These individuals have two or more islet autoantibodies and have lost enough beta cells to become glucose intolerant. The 5-year risk for frank type 1 diabetes at this stage is approximately 75% at 5 years and nearly 100% thereafter.
Stage 3: Symptomatic type 1 diabetes. The individual demonstrates typical clinical symptoms and signs of diabetes, including polyuria, polydipsia, weight loss, fatigue, and diabetic ketoacidosis (DKA).
In natural-history studies, short-term benefits from the use of such staging have included reductions in DKA and hospitalization at symptomatic-disease onset and improved glycemic control with a greater chance of experiencing a "honeymoon" period in which the requirement for exogenous insulin is temporarily blunted.
Dr Insel and colleagues write, "Risk screening and staging as outlined here are not recommended at this time for clinical practice in the absence of cost-effective screening, staging, and effective interventions that delay progression to symptomatic type 1 diabetes."
However, they add, "This classification system, which will be continuously refined with the development of novel stage-specific biomarkers, provides a new taxonomy of type 1 diabetes and a framework for clinical trial design, benefit/risk decisions around interventions, and, ultimately, the practice of precision medicine to prevent symptomatic type 1 diabetes."
The staging approach has been endorsed by The American Association of Clinical Endocrinologists, the Endocrine Society, the International Society for Pediatric and Adolescent Diabetes, and the Leona M and Harry B Helmsley Charitable Trust.
Diabetes Care. 38:1964-1974. Abstract
Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association
- Richard A. Insel1⇑,
- Jessica L. Dunne1,
- Mark A. Atkinson2,
- Jane L. Chiang3,
- Dana Dabelea4,
- Peter A. Gottlieb5,
- Carla J. Greenbaum6,
- Kevan C. Herold7,
- Jeffrey P. Krischer8,
- Åke Lernmark9,
- Robert E. Ratner3,
- Marian J. Rewers5,
- Desmond A. Schatz2,
- Jay S. Skyler10,
- Jay M. Sosenko10 and
- Anette-G. Ziegler11
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.
The full paper
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