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.
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.
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.
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.
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The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
- AUCINS/GLU :
Cystic fibrosis-related diabetes
CF transmembrane conductance regulator
Forced expiratory volume in 1 s
- GAUC :
Total AUC for glucose
- Gmax :
Peak OGTT glucose
- IAUC :
Total AUC for insulin
Impaired glucose tolerance
- Imax :
Peak OGTT insulin
Insulin sensitivity index
Montreal Cystic Fibrosis Cohort
Normal glucose tolerance
Panagopoulou P, Fotoulaki M, Nikolaou A, Nousia-Arvanitakis S (2014) Prevalence of malnutrition and obesity among cystic fibrosis patients. Pediatr Int 56(1):89–94. https://doi.org/10.1111/ped.12214
Fibrose Kystique Canada (2018) Rapport de données annuel 2017 du Registre canadien sur la fibrose kystique. Available from http://www.fibrosekystique.ca/about-us/rapport-annuel. Accessed 16 Jan 2020 [document in French]
Corey M, McLaughlin FJ, Williams M, Levison H (1988) A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol 41(6):583–591. https://doi.org/10.1016/0895-4356(88)90063-7
Clancy JP (2018) Rapid therapeutic advances in CFTR modulator science. Pediatr Pulmonol 53(S3):S4–S11. https://doi.org/10.1002/ppul.24157
Bell SC, Mall MA, Gutierrez H et al (2020) The future of cystic fibrosis care: a global perspective. Lancet Respir Med 8(1):65–124. https://doi.org/10.1016/S2213-2600(19)30337-6
Boudreau V, Coriati A, Hammana I et al (2016) Variation of glucose tolerance in adult patients with cystic fibrosis: what is the potential contribution of insulin sensitivity? J Cyst Fibros 15(6):839–845. https://doi.org/10.1016/j.jcf.2016.04.004
Costa M, Potvin S, Berthiaume Y et al (2005) Diabetes: a major co-morbidity of cystic fibrosis. Diabetes Metab 31(3 Pt 1):221–232. https://doi.org/10.1016/s1262-3636(07)70189-1
Moran A, Pekow P, Grover P et al (2009) Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis related diabetes therapy trial. Diabetes Care 32(10):1783–1788. https://doi.org/10.2337/dc09-0585
Rafii M, Chapman K, Stewart C et al (2005) Changes in response to insulin and the effects of varying glucose tolerance on whole-body protein metabolism in patients with cystic fibrosis. Am J Clin Nutr 81(2):421–426. https://doi.org/10.1093/ajcn.81.2.421
Stephenson AL, Mannik LA, Walsh S et al (2013) Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: a population-based cohort study. Am J Clin Nutr 97(4):872–877. https://doi.org/10.3945/ajcn.112.051409
Bonhoure A, Boudreau V, Litvin M et al (2020) Overweight, obesity and significant weight gain in adult patients with cystic fibrosis association with lung function and cardiometabolic risk factors. Clin Nutr 39(9):2910–2916
Brennan AL, Gyi KM, Wood DM et al (2007) Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis. J Cyst Fibros 6(2):101–109. https://doi.org/10.1016/j.jcf.2006.03.009
Ntimbane T, Krishnamoorthy P, Huot C et al (2008) Oxidative stress and cystic fibrosis-related diabetes: a pilot study in children. J Cyst Fibros 7(5):373–384. https://doi.org/10.1016/j.jcf.2008.01.004
Lanng S, Thorsteinsson B, Nerup J, Koch C (1994) Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections. Acta Paediatr 83(8):849–853. https://doi.org/10.1111/j.1651-2227.1994.tb13156.x
Godbout A, Hammana I, Potvin S et al (2008) No relationship between mean plasma glucose and glycated haemoglobin in patients with cystic fibrosis-related diabetes. Diabetes Metab 34(6 Pt 1):568–573. https://doi.org/10.1016/j.diabet.2008.05.010
Moran A, Brunzell C, Cohen RC et al (2010) Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care 33(12):2697–2708. https://doi.org/10.2337/dc10-1768
Walshaw M (2009) Routine OGTT screening for CFRD - no thanks. J R Soc Med 102(Suppl 1):40–44
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15(7):539–553. https://doi.org/10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
Sylvain C, Lamothe L, Berthiaume Y, Rabasa-Lhoret R (2016) How patients’ representations of cystic fibrosis-related diabetes inform their health behaviours. Psychol Health 31(10):1129–1144. https://doi.org/10.1080/08870446.2016.1183008
Coriati A, Belson L, Ziai S et al (2014) Impact of sex on insulin secretion in cystic fibrosis. J Clin Endocrinol Metab 99(5):1767–1773. https://doi.org/10.1210/jc.2013-2756
Stumvoll M, Mitrakou A, Pimenta W et al (2000) Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23(3):295–301. https://doi.org/10.2337/diacare.23.3.295
Prentice BJ, Chelliah A, Ooi CY et al (2019) Peak OGTT glucose is associated with lower lung function in young children with cystic fibrosis. J Cyst Fibros 19(2):305–309
Brodsky J, Dougherty S, Makani R, Rubenstein RC, Kelly A (2011) Elevation of 1-hour plasma glucose during oral glucose tolerance testing is associated with worse pulmonary function in cystic fibrosis. Diabetes Care 34(2):292–295. https://doi.org/10.2337/dc10-1604
Hameed S, Morton JR, Jaffe A et al (2010) Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain. Diabetes Care 33(2):221–226. https://doi.org/10.2337/dc09-1492
Boudreau V, Reynaud Q, Bonhoure A, Durieu I, Rabasa-Lhoret R (2019) Validation of a stepwise approach using glycated hemoglobin levels to reduce the number of required oral glucose tolerance tests to screen for cystic fibrosis–related diabetes in adults. Can J Diabetes 43(3):161–162. https://doi.org/10.1016/j.jcjd.2018.11.005
Sheikh S, Gudipaty L, De Leon DD et al (2017) Reduced beta-cell secretory capacity in pancreatic-insufficient, but not pancreatic-sufficient, cystic fibrosis despite normal glucose tolerance. Diabetes 66(1):134–144
Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ (2005) Epidemiology of cystic fibrosis-related diabetes. J Pediatr 146(5):681–687. https://doi.org/10.1016/j.jpeds.2004.12.039
Boudreau V, Reynaud Q, Dubois CL et al (2016) Screening for cystic fibrosis-related diabetes: matching pathophysiology and addressing current challenges. Can J Diabetes 40(5):466–470. https://doi.org/10.1016/j.jcjd.2016.08.221
Lanng S, Thorsteinsson B, Nerup J, Koch C (1992) Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. Eur J Pediatr 151(9):684–687. https://doi.org/10.1007/BF01957574
Bismuth E, Laborde K, Taupin P et al (2008) Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis. J Pediatr 152(4):540–545, 5 e1. https://doi.org/10.1016/j.jpeds.2007.09.025
Cano Megias M, Guisado Vasco P, Gonzalez Albarran O, Lamas Ferreiro A, Maiz Carro L (2015) Association of the relative change in weight and body mass index with lung function in teenagers and adults with cystic fibrosis: Influence of gender and diabetes. Endocrinol Nutr 62(9):422–429. https://doi.org/10.1016/j.endonu.2015.06.009
Colomba J, Boudreau V, Lehoux-Dubois C et al (2019) The main mechanism associated with progression of glucose intolerance in older patients with cystic fibrosis is insulin resistance and not reduced insulin secretion capacity. J Cyst Fibros 18(4):551–556. https://doi.org/10.1016/j.jcf.2019.01.009
Kern AS, Prestridge AL (2013) Improving screening for cystic fibrosis-related diabetes at a pediatric cystic fibrosis program. Pediatrics 132(2):e512–e518. https://doi.org/10.1542/peds.2012-4029
Dobson L, Sheldon CD, Hattersley AT (2004) Conventional measures underestimate glycaemia in cystic fibrosis patients. Diabet Med 21(7):691–696. https://doi.org/10.1111/j.1464-5491.2004.01219.x
Hameed S, Jaffe A, Verge CF (2015) Advances in the detection and management of cystic fibrosis related diabetes. Curr Opin Pediatr 27(4):525–533. https://doi.org/10.1097/MOP.0000000000000251
Coriati A, Elisha B, Virassamynaik S et al (2013) Diagnosis of cystic fibrosis-related glucose abnormalities: can we shorten the standard oral glucose tolerance test? Appl Physiol Nutr Metab 38(12):1254–1259. https://doi.org/10.1139/apnm-2013-0022
Quon BS, Sykes J, Stanojevic S et al (2018) Clinical characteristics of cystic fibrosis patients prior to lung transplantation: an international comparison between Canada and the United States. Clin Transpl 32(3):e13188. https://doi.org/10.1111/ctr.13188
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.
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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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
- Blood glucose variables
- Cystic fibrosis
- Lung function
- Oral glucose tolerance test