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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...

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Main Authors: Sandforth, Arvid (Author) , Arreola, Elsa Vazquez (Author) , Hanson, Robert L. (Author) , Wewer Albrechtsen, Nicolai J. (Author) , Holst, Jens Juul (Author) , Ahrends, Robert (Author) , Coman, Cristina (Author) , Gerst, Felicia (Author) , Lorza-Gil, Estela (Author) , Cheng, Yurong (Author) , Sandforth, Leontine (Author) , Katzenstein, Sarah (Author) , Ganslmeier, Marlene (Author) , Seissler, Jochen (Author) , Hauner, Hans (Author) , Perakakis, Nikolaos (Author) , Wagner, Robert (Author) , Machann, Jürgen (Author) , Schick, Fritz (Author) , Peter, Andreas (Author) , Lehmann, Rainer (Author) , Weigert, Cora (Author) , Maurer, Jennifer (Author) , Preissl, Hubert (Author) , Heni, Martin (Author) , Szendrödi, Julia (Author) , Kopf, Stefan (Author) , Solimena, Michele (Author) , Schwarz, Peter (Author) , Blüher, Matthias (Author) , Häring, Hans-Ulrich (Author) , Hrabé de Angelis, Martin (Author) , Schürmann, Annette (Author) , Kabisch, Stefan (Author) , Mai, Knut (Author) , Pfeiffer, Andreas F. H. (Author) , Bornstein, Stefan (Author) , Stumvoll, Michael (Author) , Roden, Michael (Author) , Stefan, Norbert (Author) , Fritsche, Andreas (Author) , Birkenfeld, Andreas L. (Author) , Jumpertz von Schwartzenberg, Reiner (Author)
Format: Article (Journal)
Language:English
Published: October 2025
In: Nature medicine
Year: 2025, Volume: 31, Issue: 10, Pages: 3330-3340, [11-35]
ISSN:1546-170X
DOI:10.1038/s41591-025-03944-9
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-025-03944-9
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41591-025-03944-9
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Author Notes:Arvid Sandforth, Elsa Vazquez Arreola, Robert L. Hanson, Nicolai J. Wewer Albrechtsen, Jens Juul Holst, Robert Ahrends, Cristina Coman, Felicia Gerst, Estela Lorza-Gil, Yurong Cheng, Leontine Sandforth, Sarah Katzenstein, Marlene Ganslmeier, Jochen Seissler, Hans Hauner, Nikolaos Perakakis, Robert Wagner, Jürgen Machann, Fritz Schick, Andreas Peter, Rainer Lehmann, Cora Weigert, Jennifer Maurer, Hubert Preissl, Martin Heni, Julia Szendrödi, Stefan Kopf, Michele Solimena, Peter Schwarz, Matthias Blüher, Hans-Ulrich Häring, Martin Hrabé de Angelis, Annette Schürmann, Stefan Kabisch, Knut Mai, Andreas F. H. Pfeiffer, Stefan Bornstein, Michael Stumvoll, Michael Roden, Norbert Stefan, Andreas Fritsche, Andreas L. Birkenfeld & Reiner Jumpertz von Schwartzenberg
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Summary: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.
Item Description:Online veröffentlicht am 29. September 2025
Gesehen am 17.04.2026
Physical Description:Online Resource
ISSN:1546-170X
DOI:10.1038/s41591-025-03944-9

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