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Publications

Journal Article Ahead of print

PubMed: 42803375 DOI: 10.2337/dci26-0142

Insulin Resistance in the 21st Century: New Takes on an Old Problem-2025 Diabetes, Diabetes Care, and Diabetologia Expert Forum.

Diabetes Care

Authors: Amalia Gastaldelli, Eunhee Choi, Karin Conde-Knape, Olga Göransson, Anna Krook, Sanna Lehtonen, Michael Roden, Patrick Schrauwen, Lauren M Sparks, Martin Heni

Affiliations

  • Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy.
  • Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
  • Valo Health, Boston, MA.
  • Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Department of Pathology, University of Helsinki, Helsinki, Finland.
  • Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland.
  • Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
  • German Center for Diabetes Research, Partner Düsseldorf,Neuherberg, Germany.
  • Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
  • Translational Research Institute, Advent Health, Orlando, FL.
  • Division of Endocrinology and Diabetology, Department of Internal Medicine 1, University Hospital Ulm, Ulm, Germany.
  • Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.

Abstract

Insulin resistance is a hallmark of type 2 diabetes and several other metabolic diseases. However, efforts to improve insulin resistance are hindered by the biological complexity inherent to insulin action, as well as conceptual and methodological limitations to date. In September 2025, the editors of Diabetes, Diabetes Care, and Diabetologia convened an Expert Forum in advance of the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD). Participants reviewed the latest research, clarified key concepts, and recommended future research priorities. Their insights were presented at a symposium during the EASD meeting and are offered in more detail here. The authors challenge the historical view of insulin resistance as a single, uniform pathophysiological condition, describing it instead as a diverse and highly plastic set of adaptive, maladaptive, acute, and chronic responses that manifest differently throughout the body, in numerous biological processes, within and among individuals, and under various physiological and environmental conditions. They describe existing methods of measuring whole-body and tissue-specific insulin resistance and offer a primer on the two main insulin signaling networks. Next, they review current therapeutic options, which offer mostly indirect effects on insulin resistance, and highlight promising strategies to inform the eventual development of true insulin-sensitizing agents. The authors call for continued investigation of the complex factors accounting for variability in insulin resistance, as well as pathway-specific defects, with the ultimate goal of developing targeted and more effective therapies for type 2 diabetes and the broader spectrum of cardiometabolic complications and related comorbidities.

MeSH

Diabetes Mellitus, Insulin Resistance, Insulin, Research, Therapeutics, Diabetes Mellitus, Type 2