Abstract
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.
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 3330-3340 |
| Seitenumfang | 11 |
| Fachzeitschrift | Nature Medicine |
| Jahrgang | 31 |
| Ausgabenummer | 10 |
| Frühes Online-Datum | 2025 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - Okt. 2025 |
Fördermittel
Additionally, this work was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The DPP was conducted by the DPP Research Group and supported by the NIDDK, the General Clinical Research Center Program, the National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women’s Health, the Office of Research on Minority Health, the Centers for Disease Control and Prevention and the ADA. Mass spectrometry work was supported by funds of ‘Bundesministerium für Bildung, Wissenschaft und Forschung’ (BMBFW) within the project DigiOmics4Austria ( https://bit.ly/44A30s1 , to R.A.). The authors gratefully acknowledge the support provided by the Mass Spectrometry Centre at the Faculty of Chemistry, University of Vienna. The data (and biospecimens) from the DPP were supplied by the NIDDK Central Repository. This manuscript was not prepared under the auspices of the DPP and does not represent analyses or conclusions of the DPP Research Group, the NIDDK Central Repository or the NIH. The funders had no role in the design, implementation, analysis or writing up of the manuscript. S.K. receives grants from the German Diabetes Association, Wilhelm Doerenkamp Foundation and California Walnut Commission, and lecture fees from Sanofi, Boehringer Ingelheim, Berlin Chemie, Lilly Deutschland and Juzo Akademie. R.W. receives lecture fees from Eli Lilly, Novo Nordisk and Sanofi, and participates in a Data Safety Monitoring Board and Advisory Board for Eli Lilly. N.P. receives lecture fees from Novo Nordisk and Gesellschaft für Wissenschaftstransfer Dresden, advisory board fees from Bayer Vital and holds patent WO2021/092265A1 for diagnosis and treatment of nonalcoholic fatty liver disease and liver fibrosis. J.J.H. is consulting with Novo Nordisk. N.J.W.A. has received research support and speaker fees from Mercodia, Novo Nordisk, Merck/MSD and Boehringer Ingelheim. All other authors declare no competing interests. PLIS and this post hoc analysis were supported by the German Center for Diabetes Research, which is funded by the German Federal Ministry for Education and Research and the German states where its partner institutions are located (01GI0925). R.J.v.S. was supported by the Helmholtz Young Investigators Groups funding programme (Project ID: VH-NG-1619) and the Cluster of Excellence EXC 2124 (project 03.007). The study was additionally funded by a grant from the German Research Foundation (DFG; GRK2816 to A.L.B.). Part of the work was supported by the European Foundation for the Study of Diabetes Future Leader Award (NNF21SA0072746 to N.J.W.A.), Independent Research Fund Denmark (1052-00003B, 10.46540/4308-00056B and 10.46540/4285-00131B to N.J.W.A.) and Novo Nordic Foundation (NNF23OC0084970, NNF19OC0055001 and NNF24OC0088402 to N.J.W.A.). K.M. was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation (DFG))—CRG/TRR 412. A.S. and L.S. are supported by the DFG Clinician Scientist Program ‘MINT-CS’ of the Medical Faculty of the University of Tübingen.
UN SDGs
Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung
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SDG 3 – Gesundheit und Wohlergehen
ÖFOS 2012
- 301305 Medizinische Chemie
- 301303 Medizinische Biochemie
- 301114 Zellbiologie
- 106005 Bioinformatik
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