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Lookup NU author(s): Professor James ShawORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Aims/hypothesis: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. Methods: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. Results: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). Conclusions/interpretation: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance. Graphical Abstract: (Figure presented.)
Author(s): Nielsen BU, Mathiesen IHM, Krogh-Madsen R, Katzenstein TL, Pressler T, Shaw JAM, Rickels MR, Almdal TP, Faurholt-Jepsen D, Stefanovski D
Publication type: Article
Publication status: Published
Journal: Diabetologia
Year: 2024
Volume: 67
Pages: 2188-2198
Print publication date: 01/10/2024
Online publication date: 02/08/2024
Acceptance date: 23/05/2024
Date deposited: 03/09/2025
ISSN (print): 0012-186X
ISSN (electronic): 1432-0428
Publisher: Springer Science and Business Media Deutschland GmbH
URL: https://doi.org/10.1007/s00125-024-06220-6
DOI: 10.1007/s00125-024-06220-6
Data Access Statement: The datasets generated during and/or analysed during the current study are not publicly available due to reasons of sensitivity and data protection regulations but are available from the corresponding author upon reasonable request. Data are located in controlled access data storage in REDCap at Region Hovedstaden, Denmark.
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