Prevention of type 2 diabetes through prediabetes remission without weight loss
Clinical practice guidelines recommend defined weight loss goals for the prevention of type 2 diabetes (T2D) in those individuals with increased risk, such as prediabetes. However, achieving prediabetes remission, that is, reaching normal glucose regulation according to American Diabetes Association criteria, is more efficient in preventing T2D than solely reaching weight loss goals. Here we present a post hoc analysis of the large, multicenter, randomized, controlled Prediabetes Lifestyle Intervention Study (PLIS), demonstrating that prediabetes remission is achievable without weight loss or even weight gain, and that it also protects against incident T2D. The underlying mechanisms include improved insulin sensitivity, β-cell function and increments in β-cell-GLP-1 sensitivity. Weight gain was similar in those achieving prediabetes remission (responders) compared with nonresponders; however, adipose tissue was differentially redistributed in responders and nonresponders when compared against each other-while nonresponders increased visceral adipose tissue mass, responders increased adipose tissue in subcutaneous depots. The findings were reproduced in the US Diabetes Prevention Program. These data uncover essential pathways for prediabetes remission without weight loss and emphasize the need to include glycemic targets in current clinical practice guidelines to improve T2D prevention.
Authors
- Norbert Stefan (ORCID: https://orcid.org/0000-0002-2186-9595)
- Martin Hrabě de Angelis (ORCID: https://orcid.org/0000-0002-7898-2353)
- Stefan R. Bornstein (ORCID: https://orcid.org/0000-0002-5211-2536)
- Martin Heni (ORCID: https://orcid.org/0000-0002-8462-3832)
- Jochen Seißler (ORCID: https://orcid.org/0000-0002-7404-2364)
- Elsa Vazquez Arreola (ORCID: https://orcid.org/0000-0003-1960-1159)
- Andreas L. Birkenfeld (ORCID: https://orcid.org/0000-0003-1407-9023)
- Knut Mai (ORCID: https://orcid.org/0000-0003-0126-3155)
- Jürgen Machann (ORCID: https://orcid.org/0000-0002-4458-5886)
- Róbert Wágner (ORCID: https://orcid.org/0000-0002-6120-0191)
- Andreas Peter (ORCID: https://orcid.org/0000-0001-5732-2287)
- Marlene Ganslmeier
- Michael Roden (ORCID: https://orcid.org/0000-0001-8200-6382)
- Jennifer Maurer (ORCID: https://orcid.org/0000-0002-4539-3173)
- Nikolaos Perakakis (ORCID: https://orcid.org/0000-0002-2319-6603)
- Fritz Schick (ORCID: https://orcid.org/0000-0002-4231-3406)
- Cristina Coman (ORCID: https://orcid.org/0000-0002-3771-2410)
- Cora Weigert (ORCID: https://orcid.org/0000-0003-0358-776X)
- Annette Schürmann (ORCID: https://orcid.org/0000-0002-4113-4377)
- Michele Solimena (ORCID: https://orcid.org/0000-0002-3653-8107)
- Julia Szendrödi
- Robert Ahrends (ORCID: https://orcid.org/0000-0003-0232-3375)
- Nicolai J. Wewer Albrechtsen (ORCID: https://orcid.org/0000-0003-4230-5753)
- Robert L. Hanson (ORCID: https://orcid.org/0000-0002-4252-7068)
- Leontine Sandforth
- Felicia Gerst
- Michael Stümvoll (ORCID: https://orcid.org/0000-0001-6225-8240)
- Stefan Kopf (ORCID: https://orcid.org/0000-0002-6455-3769)
- Stefan Kabisch (ORCID: https://orcid.org/0000-0003-1792-1757)
- Peter E. H. Schwarz (ORCID: https://orcid.org/0000-0001-6317-7880)
- Rainer Lehmann (ORCID: https://orcid.org/0000-0003-1218-6810)
- Andreas Fritsche (ORCID: https://orcid.org/0000-0002-4987-1961)
- Hubert Preißl (ORCID: https://orcid.org/0000-0002-8859-4661)
- Reiner Jumpertz von Schwartzenberg (ORCID: https://orcid.org/0000-0002-5544-099X)
- Sarah Katzenstein
- Hans Hauner (ORCID: https://orcid.org/0000-0002-1682-5088)
- Arvid Sandforth (ORCID: https://orcid.org/0009-0009-5374-1260)
- Andreas F. H. Pfeiffer (ORCID: https://orcid.org/0000-0002-6887-0016)
- Matthias Blüher (ORCID: https://orcid.org/0000-0003-0208-2065)
- Estela Lorza‐Gil
- Hans‐Ulrich Häring (ORCID: https://orcid.org/0000-0003-4655-9937)
- Jens Juul Holst (ORCID: https://orcid.org/0000-0001-6853-3805)
- Yurong Cheng
Institutions
- University of Copenhagen (DK)
- University of Vienna (AT)
- King's College London (GB)
- Heidelberg University (DE)
- Novo Nordisk Foundation (DK)
- Frederiksberg Hospital (DK)
- University Hospital Heidelberg (DE)
- Copenhagen University Hospital (DK)
- Helmholtz Zentrum München (DE)
- Humboldt-Universität zu Berlin (DE)
- Düsseldorf University Hospital (DE)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- University Hospital Schleswig-Holstein (DE)
- University Children's Hospital Tübingen (DE)
- University Hospital Leipzig (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- University Hospital Ulm (DE)
- German Center for Diabetes Research (DE)
- German Institute of Human Nutrition (DE)
- Paul Langerhans Institute Dresden (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- Technische Universität Dresden (DE)
- University of Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
- Leipzig University (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-09-29
- DOI
- https://doi.org/10.1038/s41591-025-03944-9
- Citations
- 15
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 17.46