Peak glucose during an oral glucose tolerance test is associated with future diabetes risk in adults with cystic fibrosis

Abstract

Aims/hypothesis

Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2 h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD.

Methods

Cross-sectional analysis at baseline (n = 293) and observational prospective analysis (n = 185; mean follow-up of 7.5 ± 4.2 years) of the Montreal Cystic Fibrosis Cohort were performed. Blood glucose and insulinaemia OGTT variables were studied in relation to lung function (forced expiratory volume in 1 s [FEV1]), BMI and risk of developing CFRD.

Results

At baseline, maximum OGTT glucose (Gmax) was negatively associated with FEV1 (p = 0.003). Other OGTT values, including classical 2 h glucose, were not. A higher Gmax was associated with lower insulin secretory capacity, delayed insulin peak timing and greater pancreatic insufficiency (p < 0.01). Gmax was positively associated with the risk of developing CFRD (p = 0.0029); no individual with a Gmax < 8 mmol/l developed CFRD over the following decade. No OGTT variable correlated to the rate of change in BMI or FEV1.

Conclusions/interpretation

In adults with CF, Gmax is strongly associated with the risk of developing CFRD; Gmax < 8 mmol/l could identify those at very low risk of future CFRD. Gmax is higher in individuals with pancreatic insufficiency and is associated with poorer insulin secretory capacity and pulmonary function.

Graphical abstract

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Fig. 1
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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AUCINS/GLU :

IAUC/GAUC

CF:

Cystic fibrosis

CFRD:

Cystic fibrosis-related diabetes

CFTR:

CF transmembrane conductance regulator

FEV1:

Forced expiratory volume in 1 s

GAUC :

Total AUC for glucose

Gmax :

Peak OGTT glucose

IAUC :

Total AUC for insulin

IGT:

Impaired glucose tolerance

Imax :

Peak OGTT insulin

ISI:

Insulin sensitivity index

MCFC:

Montreal Cystic Fibrosis Cohort

NGT:

Normal glucose tolerance

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Acknowledgements

The authors wish to thank all the nurses at the diabetes and CF clinic (Hôpital Hôtel Dieu de Montreal, Canada) for their technical assistance with the OGTTs: E. Byiringiro; L. Virlan; J. Dorion; A. Gobeil; and A. Latulippe.

Authors’ relationships and activities

The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Funding

This work was supported by the J-A DeSève diabetes research chair and a CF Canada operating grant (no. 3186), both awarded to RRL. AB holds an internal studentship from the Faculty of Medicine of McGill University. VB holds a scholarship from the Fonds de Recherche en santé du QC and from the Canadian Institutes of Health Research. JC holds a scholarship from the Québec cardiometabolic network (CMDO).

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Contributions

AB, KP, KD, MC and RRL contributed to the conception and design. AB, VB, JC, AL, FT and CB contributed to the acquisition of data. AB, KP and JC contributed to the analysis and interpretation of data. AB, KP and RRL drafted the article. AB, KP and RRL had primary responsibility for the integrity of the work as a whole. All authors read, revised critically and gave final approval of the version to be published.

Corresponding author

Correspondence to Rémi Rabasa-Lhoret.

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Bonhoure, A., Potter, K.J., Colomba, J. et al. Peak glucose during an oral glucose tolerance test is associated with future diabetes risk in adults with cystic fibrosis. Diabetologia 64, 1332–1341 (2021). https://doi.org/10.1007/s00125-021-05423-5

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Keywords

  • Adult
  • Blood glucose variables
  • Cystic fibrosis
  • Lung function
  • Oral glucose tolerance test