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Sandforth, A. ; Arreola, E.V.* ; Hanson, R.L.* ; Wewer Albrechtsen, N.J.* ; Holst, J.J.* ; Ahrends, R.* ; Coman, C.* ; Gerst, F. ; Lorza-Gil, E. ; Cheng, Y. ; Sandforth, L. ; Katzenstein, S. ; Ganslmeier, M. ; Seissler, J.* ; Hauner, H.* ; Perakakis, N. ; Wagner, R.* ; Machann, J. ; Schick, F. ; Peter, A. ; Lehmann, R. ; Weigert, C. ; Maurer, J. ; Preissl, H. ; Heni, M.* ; Szendrödi, J.* ; Kopf, S.* ; Solimena, M. ; Schwarz, P.* ; Blüher, M. ; Häring, H.-U. ; Hrabě de Angelis, M. ; Schürmann, A.* ; Kabisch, S.* ; Mai, K.* ; Pfeiffer, A.F.H.* ; Bornstein, S.* ; Stumvoll, M. ; Roden, M.* ; Stefan, N. ; Fritsche, A. ; Birkenfeld, A.L. ; Jumpertz von Schwartzenberg, R.

Prevention of type 2 diabetes through prediabetes remission without weight loss.

Nat. Med. 31, 3330-3340 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Glucagon-like Peptide-1; Beta-cell Function; Life-style Intervention; Insulin-resistance; Adipose-tissue; Oral Glucose; Fat Quantification; Lipid Extraction; Clinical-trial; Follow-up
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 31, Issue: 10, Pages: 3330-3340 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Pancreatic Islet Research (IPI)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Institute of Experimental Genetics (IEG)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP Element(s) G-502400-001
G-502600-012
G-502600-001
G-506501-001
G-500600-001
G-506500-001
Grants Helmholtz Association
DOI 10.1038/s41591-025-03944-9
WOS ID 001583171200001
Scopus ID 105017404122
PubMed ID 41023486
Erfassungsdatum 2025-10-22
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