Cystic Fibrosis-Related Diabetes

Kayani Kayani, Raihan Mohammed, Hasan Mohiaddin, Kayani Kayani, Raihan Mohammed, Hasan Mohiaddin

Abstract

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD), which affects 40-50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR) also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

Keywords: complications; cystic fibrosis; cystic fibrosis transmembrane conductance regulator; diabetes; pathophysiology; treatment.

Figures

Figure 1
Figure 1
Diagram demonstrating the complex pathogenesis associated with cystic fibrosis-related diabetes (CFRD).
Figure 2
Figure 2
Hypothesized model of normal (left) and cystic fibrosis (CF) (right) beta cells. The defect in CFTR in the CF beta cell impairs both chloride efflux and vesicle release, impairing insulin secretion, giving an insulinopenic state.

References

    1. Zvereff VV, Faruki H, Edwards M, Friedman KJ. Cystic fibrosis carrier screening in a North American population. Genet Med (2014) 16(7):539–46.10.1038/gim.2013.188
    1. Cystic Fibrosis Foundation. Helping you Live Today (2017). Available from:
    1. Frew AJ, Holgate ST. Respiratory disease. 7th ed In: Kumar P, Clark M, editors. Kumar & Clark’s Clinical Medicine. Edinburgh: Saunders; (2009). p. 844–6.
    1. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science (1989) 245(4922):1066–73.10.1126/science.2475911
    1. Gregory RJ, Cheng SH, Rich DP, Marshall J, Paul S, Hehir K, et al. Expression and characterization of the cystic fibrosis transmembrane conductance regulator. Nature (1990) 347(6291):382–6.10.1038/347382a0
    1. Briel M, Greger R, Kunzelmann K. Cl- transport by CFTR contributes to the inhibition of epithelial Na+ channels in Xenopus ooyctes coexpressing CFTR and ENaC. J Physiol (1998) 508(3):825–36.10.1111/j.1469-7793.1998.825bp.x
    1. Schwiebert EM, Benos DJ, Egan ME, Stutts MJ, Guggino WB. CFTR is a conductance regulator as well as a chloride channel. Physiol Rev (1999) 79(1 Suppl):S145–66.10.1152/physrev.1999.79.1.S145
    1. Lee MG, Choi JY, Luo X, Strickland E, Thomas PJ, Muallem S. Cystic fibrosis transmembrane conductance regulator regulates luminal Cl-/HCO3/- exchange in mouse submandibular and pancreatic ducts. J Biol Chem (1999) 274(21):14670–7.10.1074/jbc.274.21.14670
    1. Quinton PM. Cystic fibrosis: impaired bicarbonate secretion and mucoviscidosis. Lancet (2008) 372(9636):415–7.10.1016/S0140-6736(08)61162-9
    1. Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S. Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis. Nature (2001) 410(6824):94–7.10.1038/35065099
    1. Rommens JM. Cystic Fibrosis Mutation Database (2011). Available from:
    1. Wang Y, Wrennall JA, Cai Z, Li H, Sheppard DN. Understanding how cystic fibrosis mutations disrupt CFTR function: from single molecules to animal models. Int J Biochem Cell Biol (2014) 52:47–57.10.1016/j.biocel.2014.04.001
    1. Cystic Fibrosis Foundation. Cystic Fibrosis Foundation Patient Registry Annual Data Report (2013). p. 1–15. Available from:
    1. National Guideline Alliance (UK). Cystic Fibrosis: Diagnosis and Management. London: National Institute for Health and Care Excellence (UK) (2017).
    1. Stephenson AL, Sykes J, Stanojevic S, Quon BS, Marshall BC, Petren K, et al. Survival comparison of patients with cystic fibrosis in Canada and the United States: a population-based cohort study. Ann Intern Med (2017) 166:537–46.10.7326/M16-0858
    1. Moran A, Dunitz J, Nathan B, Saeed A, Holme B, Thomas W. Cystic fibrosis-related diabetes: current trends in prevalence, incidence, and mortality. Diabetes Care (2009) 32(9):1626–31.10.2337/dc09-0586
    1. Finkelstein SM, Wielinski CL, Elliott GR, Warwick WJ, Barbosa J, Wu SC, et al. Diabetes mellitus associated with cystic fibrosis. J Pediatr (1988) 112(3):373–7.10.1016/S0022-3476(88)80315-9
    1. Milla CE, Billings J, Moran A. Diabetes is associated with dramatically decreased survival in female but not male subjects with cystic fibrosis. Diabetes Care (2005) 28(9):2141–4.10.2337/diacare.28.9.2141
    1. Sims E, Green M, Mehta A. Decreased lung function in female but not male subjects with established cystic fibrosis-related diabetes. Diabetes Care (2005) 28(7):1581–7.10.2337/diacare.28.7.1581
    1. Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ, et al. Epidemiology of cystic fibrosis-related diabetes. J Pediatr (2005) 146(5):681–7.10.1016/j.jpeds.2004.12.039
    1. Konrad K, Scheuing N, Badenhoop K, Borkenstein MH, Gohlke B, Söchfl C, et al. Cystic fibrosis-related diabetes compared with type 1 and type 2 diabetes in adults. Diabetes Metab Res Rev (2013) 29(7):568–75.10.1002/dmrr.2429
    1. Gottlieb PA, Yu L, Babu S, Wenzlau J, Bellin M, Frohnert BI, et al. No relation between cystic fibrosis-related diabetes and type 1 diabetes autoimmunity. Diabetes Care (2012) 35(8):2012.10.2337/dc11-2327
    1. Minicucci L, Cotellessa M, Pittaluga L, Minuto N, d’Annunzio G, Avanzini MA, et al. Beta-cell autoantibodies and diabetes mellitus family history in cystic fibrosis. J Pediatr Endocrinol Metab (2005) 18(8):755–60.10.1515/JPEM.2005.18.8.755
    1. Best L. Glucose-induced electrical activity in rat pancreatic beta-cells: dependence on intracellular chloride concentration. J Physiol (2005) 568(Pt 1):137–44.10.1113/jphysiol.2005.093740
    1. Boom A, Lybaert P, Pollet J-F, Jacobs P, Jijakli H, Golstein PE, et al. Expression and localization of cystic fibrosis transmembrane conductance regulator in the rat endocrine pancreas. Endocrine (2007) 32(2):197–205.10.1007/s12020-007-9026-x
    1. Lanng S, Thorsteinsson B, Røder ME, Orskov C, Holst JJ, Nerup J, et al. Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance. Acta Endocrinol (1993) 128(3):207–14.10.1530/acta.0.1280207
    1. Huang WQ, Guo JH, Zhang XH, Yu MK, Chung YW, Ruan YC, et al. Glucose-sensitive CFTR suppresses glucagon secretion by potentiating KATP channels in pancreatic islet α cells. Endocrinology (2017) 158(10):3188–99.10.1210/en.2017-00282
    1. Guo JH, Chen H, Ruan YC, Zhang XL, Zhang XH, Fok KL, et al. Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR. Nat Commun (2014) 5:1–10.10.1038/ncomms5420
    1. Ntimbane T, Mailhot G, Spahis S, Rabasa-Lhoret R, Kleme M-L, Melloul D, et al. CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response. Am J Physiol Endocrinol Metab (2016) 310(3):E200–12.10.1152/ajpendo.00333.2015
    1. Yang S-N, Berggren P-O. Beta-cell CaV channel regulation in physiology and pathophysiology. Am J Physiol Endocrinol Metab (2005) 288(1):E16–28.10.1152/ajpendo.00042.2004
    1. Jing X, Li D, Olofsson C. CaV2. 3 calcium channels control second-phase insulin release. J Clin Invest (2005) 115(1):146–54.10.1172/JCI200522518.146
    1. Sun X, Yi Y, Xie W, Liang B, Winter MC, He N, et al. CFTR influences beta cell function and insulin secretion through non-cell autonomous exocrine-derived factors. Endocrinology (2017) 158(10):3325–38.10.1210/en.2017-00187
    1. Yi Y, Sun X, Gibson-Corley K, Xie W, Liang B, He N, et al. A transient metabolic recovery from early life glucose intolerance in cystic fibrosis ferrets occurs during pancreatic remodeling. Endocrinology (2016) 157(5):1852–65.10.1210/en.2015-1935
    1. Galli F, Battistoni A, Gambari R, Pompella A, Bragonzi A, Pilolli F, et al. Oxidative stress and antioxidant therapy in cystic fibrosis. Biochim Biophys Acta (2012) 1822(5):690–713.10.1016/j.bbadis.2011.12.012
    1. Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease. Am J Dis Child (1938) 56(2):344.10.1001/archpedi.1938.01980140114013
    1. Wilschanski M, Novak I. The cystic fibrosis of exocrine pancreas. Cold Spring Harbor Perspect Med (2013) 3(5):a009746.10.1101/cshperspect.a009746
    1. Ahmed N, Corey M, Forstner G, Zielenski J, Tsui L-C, Ellis L, et al. Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas. Gut (2003) 52(8):1159–64.10.1136/gut.52.8.1159
    1. Geffner ME, Lippe BM, Kaplan SA, Itami RM, Gillard BK, Levin SR, et al. Carbohydrate tolerance in cystic fibrosis is closely linked to pancreatic exocrine function. Pediatr Res (1984) 18(11):1107–11.10.1203/00006450-198411000-00011
    1. Lanng S, Thorsteinsson B, Erichsen G, Nerup J, Koch C. Glucose tolerance in cystic fibrosis. Arch Dis Child (1991) 66:612–6.10.1136/adc.66.5.612
    1. Kopelman H, Corey M, Gaskin K, Durie P, Weizman Z, Forstner G. Impaired chloride secretion, as well as bicarbonate secretion, underlies the fluid secretory defect in the cystic fibrosis pancreas. Gastroenterology (1988) 95(2):349–55.10.1016/0016-5085(88)90490-8
    1. Kopelman H, Durie P, Gaskin K, Weizman Z, Forstner G. Pancreatic fluid secretion and protein hyperconcentration in cystic fibrosis. N Engl J Med (1985) 312(6):329–34.10.1056/NEJM198502073120601
    1. Tucker J, Spock A, Spicer S, Shelburne J, Bradford W. Inspissation of pancreatic zymogen material in cystic fibrosis. Ultrastruct Pathol (2003) 27(5):323–35.10.1080/716100784
    1. Brennan AL, Beynon J. Clinical updates in cystic fibrosis-related diabetes. Semin Respir Crit Care Med (2015) 1(212):236–50.
    1. Barrio R. Management of endocrine disease: cystic fibrosis-related diabetes: novel pathogenic insights opening new therapeutic avenues. Eur J Endocrinol (2015) 172(4):R131–41.10.1530/EJE-14-0644
    1. Meyerholz DK, Stoltz DA, Pezzulo AA, Welsh MJ. Pathology of gastrointestinal organs in a porcine model of cystic fibrosis. Am J Pathol (2010) 176(3):1377–89.10.2353/ajpath.2010.090849
    1. Moheet A, Moran A. CF-related diabetes: containing the metabolic miscreant of cystic fibrosis. Pediatr Pulmonol (2017) 52(S48):S37–43.10.1002/ppul.23762
    1. Imrie JR, Fagan DG, Sturgess JM. Quantitative evaluation of the development of the exocrine pancreas in cystic fibrosis and control infants. Am J Pathol (1979) 95(3):697–708.
    1. Soave D, Miller MR, Keenan K, Li W, Gong J, Ip W, et al. Evidence for a causal relationship between early exocrine pancreatic disease and cystic fibrosis-related diabetes: a Mendelian randomization study. Diabetes (2014) 63(6):2114–9.10.2337/db13-1464
    1. Löhr M, Goertchen P, Nizze H, Gould NS, Gould VE, Oberholzer M, et al. Cystic fibrosis associated islet changes may provide a basis for diabetes – an immunocytochemical and morphometrical study. Virchows Archiv A Pathol Anatomy Histopathol (1989) 414(2):179–85.10.1007/BF00718598
    1. Horowitz M, Edelbroek MA, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia (1993) 36(9):857–62.10.1007/BF00400362
    1. Symonds EL, Omari TI, Webster JM, Davidson GP, Butler RN. Relation between pancreatic lipase activity and gastric emptying rate in children with cystic fibrosis. J Pediatr (2003) 143(6):772–5.10.1067/S0022-3476(03)00581-X
    1. Guarner L, Rodríguez R, Guarner F, Malagelada JR. Fate of oral enzymes in pancreatic insufficiency. Gut (1993) 34(5):708–12.10.1136/gut.34.5.708
    1. Kuo P, Stevens JE, Russo A, Maddox A, Wishart JM, Jones KL, et al. Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis – effects of pancreatic enzyme supplementation. J Clin Endocrinol Metab (2011) 96(5):851–5.10.1210/jc.2010-2460
    1. Hillman M, Eriksson L, Mared L, Helgesson K, Landin-Olsson M. Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. J Cyst Fibros (2012) 11(2):144–9.10.1016/j.jcf.2011.11.001
    1. Rolon MA, Benali K, Munck A, Navarro J, Clement A, Tubiana-Rufi N, et al. Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and effects of insulin therapy. Acta Paediatr (2001) 90(8):860–7.10.1080/08035250152509555
    1. Lanng S, Thorsteinsson B, Nerup J, Koch C. Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. Eur J Pediatr (1992) 15:684–7.
    1. Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med (2000) 162(3 Pt 1):891–5.10.1164/ajrccm.162.3.9904075
    1. Alicandro G, Battezzati PM, Battezzati A, Speziali C, Claut L, Motta V, et al. Insulin secretion, nutritional status and respiratory function in cystic fibrosis patients with normal glucose tolerance. Clin Nutr (2012) 31(1):118–23.10.1016/j.clnu.2011.09.007
    1. Konstan MW, Hilliard KA, Norvell TM, Berger M. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am J Respir Crit Care Med (1994) 150(2):448–54.10.1164/ajrccm.150.2.8049828
    1. Bruce MC, Poncz L, Klinger JD, Stern RC, Tomashefski JF, Jr, Dearborn DG. Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis. Am Rev Respir Dis (1985) 132(3):529–35.
    1. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med (1995) 151(4):1075–82.10.1164/ajrccm.151.4.7697234
    1. Birrer P, Mcelvaney NG, Rüdeberg A, Wirz Sommer C, Liechti-Gallati S, Kraemer R, et al. Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Am J Respir Crit Care Med (1994) 150(1):207–13.10.1164/ajrccm.150.1.7912987
    1. Hardin DS, LeBlanc A, Lukenbaugh S, Para L, Seilheimer DK. Proteolysis associated with insulin resistance in cystic fibrosis. Pediatrics (1998) 101(3 Pt 1):433–7.10.1542/peds.101.3.433
    1. Stephenson AL, Mannik LA, Walsh S, Brotherwood M, Robert R, Darling PB, et al. 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 (2013) 97(4):872–7.10.3945/ajcn.112.051409
    1. Lange P, Groth S, Kastrup J, Mortensen J, Appleyard M, Nyboe J, et al. Diabetes mellitus, plasma glucose and lung function in a cross-sectional population study. Eur Respir J (1989) 2(1):14–9.
    1. Sandler M, Bunn AE, Stewart RI. Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus. Am Rev Respir Dis (1987) 135(1):223–9.
    1. Sandler M, Bunn AE, Stewart RI. Pulmonary function in young insulin-dependent diabetic subjects. Chest (1986) 90(5):670–5.10.1378/chest.90.5.670
    1. Primhak RA, Whincup G, Tsanakas JN, Milner RDG. Reduced vital capacity in insulin-dependent diabetes. Diabetes (1987) 36(3):324–6.10.2337/diabetes.36.3.324
    1. Ofulue AF, Kida K, Thurlbeck WM. Experimental diabetes and the lung. I. Changes in growth, morphometry, and biochemistry. Am Rev Respir Dis (1988) 137(1):162–6.10.1164/ajrccm/137.1.162
    1. Vracko R, Thorning D, Huang TW. Basal lamina of alveolar epithelium and capillaries: quantitative changes with aging and in diabetes mellitus. Am Rev Respir Dis (1979) 120:973–83.
    1. Ofulue AF, Thurlbeck WM. Experimental diabetes and the lung. II. In vivo connective tissue metabolism. Am Rev Respir Dis (1988) 138(2):284–9.10.1164/ajrccm/138.2.284
    1. Cavan DA, Parkes A, O’Donnell MJ, Freeman W, Cayton RM. Lung function and diabetes. Respir Med (1991) 85(3):257–8.10.1080/13518040701205365
    1. Widger J, Ranganathan S, Robinson PJ. Progression of structural lung disease on CT scans in children with cystic fibrosis related diabetes. J Cyst Fibros (2013) 12(3):216–21.10.1016/j.jcf.2012.09.005
    1. Schwarzenberg SJ, Thomas W, Olsen TW, Grover T, Walk D, Milla C, et al. Microvascular complications in cystic fibrosis-related diabetes. Diabetes Care (2007) 30(5):1056–61.10.2337/dc06-1576
    1. Wanke T, Formanek D, Auinger M, Popp W, Zwick H, Irsigler K. Inspiratory muscle performance and pulmonary function changes in insulin-dependent diabetes mellitus. Am Rev Respir Dis (1991) 143(1):97–100.10.1164/ajrccm/143.1.97
    1. Lazarus R, Sparrow D, Weiss ST. Handgrip strength and insulin levels: cross-sectional and prospective associations in the Normative Aging Study. Metabolism (1997) 46(11):1266–9.10.1016/S0026-0495(97)90228-6
    1. Wood DM, Brennan AL, Philips BJ, Baker EH. Effect of hyperglycaemia on glucose concentration of human nasal secretions. Clin Sci (2004) 106(5):527–33.10.1042/CS20030333
    1. Brennan AL, Gyi KM, Wood DM, Johnson J, Holliman R, Baines DL, et al. Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis. J Cyst Fibros (2007) 6(2):101–9.10.1016/j.jcf.2006.03.009
    1. Philips BJ, Redman J, Brennan A, Wood D, Holliman R, Baines D, et al. Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients. Thorax (2005) 60:761–4.10.1136/thx.2004.035766
    1. Merlo CA, Boyle MP, Diener-West M, Marshall BC, Goss CH, Lechtzin N. Incidence and risk factors for multiple antibiotic-resistant Pseudomonas aeruginosa in cystic fibrosis. Chest (2007) 132(2):562–8.10.1378/chest.06-2888
    1. Garnett JP, Gray MA, Tarran R, Brodlie M, Ward C, Baker EH, et al. Elevated paracellular glucose flux across cystic fibrosis airway epithelial monolayers is an important factor for Pseudomonas aeruginosa growth. PLoS One (2013) 8(10):e76283.10.1371/journal.pone.0076283
    1. Hunt WR, Zughaier SM, Guentert DE, Shenep MA, Koval M, McCarty NA, et al. Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes. Am J Physiol Lung Cell Mol Physiol (2014) 306(1):L43–9.10.1152/ajplung.00224.2013
    1. O’Shea D, O’Connell J. Cystic fibrosis related diabetes. Curr Diab Rep (2014) 14(8):511.10.1007/s11892-014-0511-3
    1. Figueroa V, Milla C, Parks EJ, Schwarzenberg SJ, Moran A. Abnormal lipid concentrations in cystic fibrosis. Am J Clin Nutr (2002) 75(6):1005–11.
    1. Perrin FMR, Serino W. Ischaemic heart disease – a new issue in cystic fibrosis? J R Soc Med (2010) 103(Suppl):S44–8.10.1258/jrsm.2010.s11010
    1. Onady GM, Farinet CL. An adult cystic fibrosis patient presenting with persistent dyspnea: case report. BMC Pulm Med (2006) 6:9.10.1186/1471-2466-6-9
    1. Andersen HU, Lanng S, Pressler T, Laugesen CS, Mathiesen ER. Cystic fibrosis-related diabetes: the presence of microvascular diabetes complications. Diabetes Care (2006) 29(12):2660–3.10.2337/dc06-0654
    1. van den Berg JMW, Morton AM, Kok SW, Pijl H, Conway SP, Heijerman HGM. Microvascular complications in patients with cystic fibrosis-related diabetes (CFRD). J Cyst Fibros (2008) 7(6):515–9.10.1016/j.jcf.2008.05.008
    1. Yung B, Landers A, Mathalone B, Gyi KM, Hudson ME. Diabetic retinopathy in adult patients with cystic fibrosis-related diabetes. Respir Med (1998) 92(6):871–2.10.1016/S0954-6111(98)90390-0
    1. Nazareth D, Walshaw M. A review of renal disease in cystic fibrosis. J Cyst Fibrosis (2013) 12:309–17.10.1016/j.jcf.2013.03.005
    1. Berg K, Ryom L, Faurholt-Jepsen D, Pressler T, Katzenstein T. Prevalence and characteristics of chronic kidney disease among Danish adults with cystic fibrosis. J Cyst Fibros (2017).10.1016/j.jcf.2017.11.001
    1. Quon B, Mayer-Hamblett N, Aitken M, Smyth A, Goss C. Risk factors for chronic kidney disease in adults with cystic fibrosis. Am J Respir Crit Care Med (2011) 184(10):1147–52.10.1164/rccm.201105-0932oc
    1. Wilcock M, Ruddick A, Gyi K, Hodson M. Renal diseases in adults with cystic fibrosis: a 40 year single centre experience. J Nephrol (2015) 28(5):585–91.10.1007/s40620-015-0179-z
    1. Mueller-Brandes C, Holl RW, Nastoll M, Ballmann M. New criteria for impaired fasting glucose and screening for diabetes in cystic fibrosis. Eur Respir J (2005) 25(4):715–7.10.1183/09031936.05.00068104
    1. Lee KMN, Miller RJH, Rosenberg FM, Kreisman SH. Evaluation of glucose tolerance in cystic fibrosis: comparison of 50-g and 75-g tests. J Cyst Fibros (2007) 6(4):274–6.10.1016/j.jcf.2006.10.008
    1. Godbout A, Hammana I, Potvin S, Mainville D, Rakel A, Berthiaume Y, et al. No relationship between mean plasma glucose and glycated haemoglobin in patients with cystic fibrosis-related diabetes. Diabetes Metab (2008) 34(6):568–73.10.1016/j.diabet.2008.05.010
    1. Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, et al. 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 (2010) 33(12):2697–708.10.2337/dc10-1768
    1. Mainguy C, Bellon G, Delaup V, Ginoux T, Kassai-Koupai B, Mazur S, et al. Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard? J Pediatr Endocrinol Metab (2017) 30(1):27–35.10.1515/jpem-2016-0184
    1. Dobson L, Sheldon CD, Hattersley AT. Conventional measures underestimate glycaemia in cystic fibrosis patients. Diabet Med (2004) 21(7):691–6.10.1111/j.1464-5491.2004.01219.x
    1. Boudreau V, Reynaud Q, Dubois CL, Coriati A, Desjardins K, Durieu I, et al. Screening for cystic fibrosis-related diabetes: matching pathophysiology and addressing current challenges. Can J Diabetes (2016) 40:466–70.10.1016/j.jcjd.2016.08.221
    1. Hameed S, Jaffé A, Verge CF. Advances in the detection and management of cystic fibrosis related diabetes. Curr Opin Pediatr (2015) 27:525–33.10.1097/MOP.0000000000000251
    1. Prentice B, Hameed S, Verge CF, Ooi CY, Jaffe A, Widger J. Diagnosing cystic fibrosis-related diabetes: current methods and challenges. Expert Rev Respir Med (2016) 10(7):799–811.10.1080/17476348.2016.1190646
    1. Bolinder J, Antuna R, Geelhoed-Duijvestijn P, Kröger J, Weitgasser R. Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial. Lancet (2016) 388(10057):2254–63.10.1016/s0140-6736(16)31535-5
    1. Soliman A, DeSanctis V, Yassin M, Elalaily R, Eldarsy N. Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups. Indian J Endocrinol Metab (2014) 18(3):274.10.4103/2230-8210.131130
    1. Martín-Frías M, Máiz L, Carcavilla A, Barrio R. Long-term benefits in lung function and nutritional status of strict metabolic control of cystic fibrosis-related diabetes. Archivos de Bronconeumología (2011) 47(10):531–4.10.1016/j.arbr.2011.06.001
    1. Perano S, Rayner CK, Couper J, Martin J, Horowitz M. Cystic fibrosis related diabetes – a new perspective on the optimal management of postprandial glycemia. J Diabetes Complications (2014) 28(6):904–11.10.1016/j.jdiacomp.2014.06.012
    1. Onady G, Stolfi A. Insulin and oral agents for managing cystic fibrosis-related diabetes. Cochrane Database Syst Rev (2016) 4:CD004730.10.1002/14651858.cd004730.pub4
    1. Tierney S, Webb K, Jones A, Dodd M, McKenna D, Rowe R, et al. Living with cystic fibrosis-related diabetes or type 1 diabetes mellitus: a comparative study exploring health-related quality of life and patients’ reported experiences of hypoglycaemia. Chronic Illn (2008) 4(4):278–88.10.1177/1742395308094240
    1. Hardin DS, Rice J, Rice M, Rosenblatt R. Use of the insulin pump in treat cystic fibrosis related diabetes. J Cystic Fibros (2009) 8(3):174–8.10.1016/j.jcf.2008.12.001
    1. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care (2012) 35(6):1364–79.10.2337/dc12-0413
    1. Doyle M, Egan J. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther (2007) 113(3):546–93.10.1016/j.pharmthera.2006.11.007
    1. Berry AJ. Pancreatic enzyme replacement therapy during pancreatic insufficiency. Nutr Clin Prac (2014) 29(3):312–21.10.1177/0884533614527773
    1. Kerem E, Reisman J, Corey M, Canny GJ, Levison H. Prediction of mortality in patients with cystic fibrosis. N Engl J Med (1992) 326(18):1187–91.10.1056/NEJM199204303261804
    1. Moran A, Phillips J, Milla C. Insulin and glucose excursion following premeal insulin lispro or repaglinide in cystic fibrosis-related diabetes. Diabetes Care (2001) 24(10):1706–10.10.2337/diacare.24.10.1706
    1. Taylor-Cousar J, Munck A, McKone E, van der Ent CK, Moeller A, Simard C, et al. Tezacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med (2017) 377(21):2013–23.10.1056/nejmoa170984
    1. Rowe S, Daines C, Ringshausen F, Kerem E, Wilson J, Tullis E, et al. Tezacaftor–ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med (2017) 377(21):2024–35.10.1056/nejmoa1709847
    1. Cohen D, Raftery J. Paying twice: questions over high cost of cystic fibrosis drug developed with charitable funding. BMJ (2014) 348:g1445.10.1136/bmj.g1445
    1. Devlin N, Parkin D. Does NICE have a cost effectiveness threshold and what other factors influence its decisions? A discrete choice analysis. Health Econ (2004) 13(5):437–52.10.1002/hec.864

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe