Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes

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, Markus LundgrenEoin 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

Research output: Contribution to journalReview article

8 Scopus citations


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 andto 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.

Original languageEnglish (US)
Pages (from-to)5-12
Number of pages8
JournalDiabetes care
Issue number1
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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    Battaglia, M., Ahmed, S., Anderson, M. S., Atkinson, M. A., Becker, D., Bingley, P. J., Bosi, E., Brusko, T. M., DiMeglio, L. A., Evans-Molina, C., Gitelman, S. E., Greenbaum, C. J., Gottlieb, P. A., Herold, K. C., Hessner, M. J., Knip, M., Jacobsen, L., Krischer, J. P., Alice Long, S., ... Peakman, M. (2020). Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes care, 43(1), 5-12.