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Wang, Y. ; Sandforth, A. ; Jumpertz von Schwartzenberg, R. ; Ganslmeier, M. ; Cheng, Y. ; Sandforth, L. ; Katzenstein, S. ; Machann, J. ; Schick, F. ; Kantartzis, K. ; Preissl, H. ; Fritsche, A. ; Stefan, N. ; Bergman, M.* ; Birkenfeld, A.L.

Lifestyle intervention is more effective in high 1-hour post-load glucose than in prediabetes for restoring β-cell function, reducing ectopic fat, and preventing type 2 diabetes.

Metabolism, DOI: 10.1016/j.metabol.2025.156430:156430 (2025)
Postprint Research data DOI PMC
Open Access Green
BACKGROUND: High 1-h-post-load plasma glucose (1 h-PG) is an early diabetes risk marker. We hypothesized that isolated high 1 h-PG represents an intermediate state between normal glucose regulation (NGR) and impaired glucose regulation (IGR) and is amendable to greater lifestyle intervention (LI) benefit. METHODS: In the Tübingen Lifestyle Intervention Program, 317 people with either NGR, IGR or isolated high 1 h-PG without IGR underwent LI for 9 months to achieve ≥5 % weight loss. RESULTS: Before LI initiation, insulin sensitivity and β-cell function declined progressively from NGR (n = 106) to high 1 h-PG (n = 96) and to IGR (n = 115). Visceral adipose tissue (VAT) volume and liver fat content increased from NGT to high 1 h-PG and to IGR. LI improved insulin sensitivity and ß-cell function in the high 1 h-PG group to levels observed in NGR together with a marked reduction in hepatic fat content. Compared to the IGR group, T2D risk was reduced by 80 % (37-96 %, p = 0.005) in the high 1 h-PG group during a 12-year follow-up period. The odds of remission to complete normoglycemia were doubled in the high 1 h-PG group compared to the IGR group (2.18 [1.13-4.28], p = 0.021). CONCLUSION: High 1 h-PG indicates an intermediate metabolic state with pathophysiological changes more severe than in NGR but milder than in IGR. In people with high 1 h-PG, LI significantly improved insulin sensitivity and β-cell function and reduced ectopic lipid deposition and the risk of developing T2D compared to IGR. These findings highlight the value of 1 h-PG as a clinically useful biomarker, providing a critical window for early intervention to reverse core metabolic defects driving prediabetes and T2D.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Ectopic Fat ; Hepatic Fat Content ; Insulin Resistance ; Masld ; Prediabetes ; Type 2 Diabetes ; β-cell Function
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 0026-0495
e-ISSN 1532-8600
Journal Metabolism: clinical and experimental
Quellenangaben Volume: , Issue: , Pages: , Article Number: 156430 Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
DOI 10.1016/j.metabol.2025.156430
PubMed ID 41192753
Erfassungsdatum 2025-11-07
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