The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.
No Thumbnail Available
Authors
EvansMolina C.
Dor Y.
Lernmark A.
Mathieu C.
Millman J.R.
Mirmira R.G.
Pociot F.
Redondo M.J.
Rich S.S.
Richardson S.J.
Check for full-text access
Issue Date
2025
Type
Article
Language
Keywords
Alternative Title
Abstract
This article summarizes the current understanding of the heterogeneity of type 1 diabetes from a June 2024 international Expert Forum organized by the editors of Diabetes, Diabetes Care, and Diabetologia. The Forum reviewed key factors contributing to the development and progression of type 1 diabetes and outlined specific, high-priority research questions. Knowledge gaps were identified, and, notably, opportunities to harness disease heterogeneity to develop personalized therapies were outlined. Herein, we summarize our discussions and review the heterogeneity of genetic risk and immunologic and metabolic phenotypes that influence and characterize type 1 diabetes progression (presented as a palette of risk factors). We discuss how these age-related factors determine disease aggres-siveness (along gradients) and describe how variable immunogenetic pathways aggregate (into networks) to affect beta-cell and other pancreatic pathologies to cause clinical disease at different ages and with variable severity (described as disease-related thresholds). Heterogeneity of pathogenesis and clinical severity opens avenues to prevention and intervention, including the potential of disease-modifying immunotherapy and islet cell replacement. We conclude with a call for 1) continued research to identify more factors contributing to the disease, both overall and in specific subgroups; 2) investigations focusing on both individuals who surpass metabolic and immune thresholds and develop diabetes and those who remain disease free with the same level of immunogenetic risk; and 3) efforts to identify where the current type 1 diabetes staging system may fall short and determine how it can be improved to capture and leverage heterogeneity in prevention and intervention strategies. Copyright © 2025 by the American Diabetes Association and the European Association for the Study of Diabetes.
Description
Citation
Publisher
License
Journal
Diabetes care
Volume
48
Issue
10