Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.


  • Manuela Battaglia
  • Simi Ahmed
  • Mark S. Anderson
  • Mark A. Atkinson
  • Dorothy Becker
  • Polly J. Bingley
  • Emanuele Bosi
  • Todd M. Brusko
  • Linda A. DiMeglio
  • Carmella Evans-Molina
  • Stephen E. Gitelman
  • Carla J. Greenbaum
  • Peter A. Gottlieb
  • Kevan C. Herold
  • Martin J. Hessner
  • Mikael Knip
  • Laura Jacobsen
  • Jeffrey P. Krischer
  • S. Alice Long
  • Eoin F. McKinney
  • Noel G. Morgan
  • Richard A. Oram
  • Tomi Pastinen
  • Michael C. Peters
  • Alessandra Petrelli
  • Xiaoning Qian
  • Maria J. Redondo
  • Bart O. Roep
  • Desmond Schatz
  • David Skibinski
  • Mark Peakman
Enheter & grupper
Externa organisationer
  • University of California, San Francisco
  • University of Bristol
  • Vita-Salute San Raffaele University
  • Indiana University
  • Yale University
  • Medical College of Wisconsin
  • Helsinki University Children's Hospital
  • University of South Florida
  • Skåne University Hospital
  • University of Cambridge
  • University of Exeter
  • Children's Mercy Hospitals and Clinics, Kansas City
  • Texas A and M University
  • Baylor College of Medicine
  • City of Hope National Medical Center
  • Leiden University Medical Centre
  • King's College London
  • King's Health Partners
  • San Raffaele Hospital
  • Juvenile Diabetes Research Foundation
  • University of Florida
  • Children's Hospital of Pittsburgh of UPMC
  • Benaroya Research Institute
  • University of Colorado
  • University of Helsinki
  • Addenbrooke's Hospital
  • Royal Devon & Exeter Hospital
  • Texas Children’s Hospital
  • San Raffaele Scientific Institute

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
Sidor (från-till)5-12
Antal sidor8
TidskriftDiabetes Care
Utgåva nummer1
StatusPublished - 2020
Peer review utfördJa