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Article History

Received: 12 August 2025

Accepted: 6 November 2025

First Online: 29 January 2026

Acknowledgements

: We wholeheartedly thank all the volunteers for participating in this study. We would also like to thank E. Abbink, A. Rasing-Hoogveld, E. Lensen, M. Eybergen, E. Sanders, E. Otters-van Bodegom, K. Theijssen, S. Ahoud and C. Slaa (all Department Clinical Research Unit, Radboud University Medical Center, Nijmegen, the Netherlands) for their assistance during the adrenaline administration, and F. Vrieling (Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands, and Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands), J. van Heck, M. Dumont and L. van Emst (all Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands) for their assistance in the lab. In addition, we would like to thank S. Teerenstra (Department of Statistics, Radboud University Medical Center, Nijmegen, the Netherlands) for his statistical assistance.

: Data supporting the findings of this study are available from the corresponding author upon reasonable request.

: This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement no. 777460. RIM is supported by a Dutch Diabetes Research Foundation Senior Fellowship, grant no. 2023.82.011. The study sponsor/funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.

: BEdG is a member of the Editorial Board of Diabetologia . The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: IFM, MSH, RS, CJT, BEdG and RIM designed the study, with the clinical and laboratory protocols designed by IFM and MSH, respectively. IFM and MSH performed the experiments and collected the data. IFM and MSH analysed and interpreted the data and drafted the manuscript. RS, CJT, BEdG and RIM critically reviewed the manuscript and provided substantial supervision. All authors discussed the results and implications and provided feedback on the manuscript at all stages. All the authors have approved the final version of the manuscript for publication. IFM, MSH and RIM are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.