Positive impact of insulin treatment on clinical trend in cystic fibrosis patients: a retrospective study

Andrea Giugno; Salvatore Leonardi; Donatella Lo Presti; Tiziana Timpanaro; Giuseppe Fabio Parisi; Maria Papale; Novella Rotolo; Sara Manti; Manuela Caruso-Nicoletti

doi:10.23750/abm.v93i5.12896

Positive impact of insulin treatment on clinical trend in cystic fibrosis patients: a retrospective study

Authors

Andrea Giugno Centro di Endocrinologia e Diabetologia Pediatrica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy https://orcid.org/0000-0002-9213-1862
Salvatore Leonardi UOC Broncopneumologia Pediatrica e Fibrosi Cistica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy https://orcid.org/0000-0002-6329-2528
Donatella Lo Presti Centro di Endocrinologia e Diabetologia Pediatrica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy
Tiziana Timpanaro Centro di Endocrinologia e Diabetologia Pediatrica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy
Giuseppe Fabio Parisi UOC Broncopneumologia Pediatrica e Fibrosi Cistica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy https://orcid.org/0000-0003-4291-0195
Maria Papale UOC Broncopneumologia Pediatrica e Fibrosi Cistica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy
Novella Rotolo UOC Broncopneumologia Pediatrica e Fibrosi Cistica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy
Sara Manti UOC Broncopneumologia Pediatrica e Fibrosi Cistica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy https://orcid.org/0000-0002-7664-3083
Manuela Caruso-Nicoletti Centro di Endocrinologia e Diabetologia Pediatrica, Università di Catania; AOU Policlinico-San Marco, Catania, Italy https://orcid.org/0000-0002-6819-605X

DOI: https://doi.org/10.23750/abm.v93i5.12896

Keywords:

Cystic Fibrosis, Diabetes, Insulin therapy, CFRD, respiratory function, BMI

Abstract

Background

Cystic fibrosis related diabetes is a complication of cystic fibrosis (CF). Aim of our study was to evaluate the effects of insulin therapy in overt diabetics or pre-diabetics CF patients on BMI and respiratory function.

Methods

We selected a sample of 17 insulin treated patients (Group T) and a sample of 17 CF control patients with normal glucose metabolism (Group C). Group T was also subdivided into overt diabetic patients and pre-diabetic patients (IGT, INDET). For treated patients an observation period was established from the first insulin administration to 12 months. For control patients, a comparable year of observation was chosen. Data regarding BMI, FVC, FEV1 and PEF were collected at time 0, and at time 12. The number of hospital admissions for infectious episodes during the year of observation and during the preceding year were recorded for Group T patients.

Results

The results showed a significant increase in BMI in treated patients compared to control, specially for overt diabetics. The study of spirometric parameters showed a significant improvement of PEF, the main effort-dependent respiratory index, specially for over diabetics, suggesting a hypothetical positive impact of the insulin anabolic action on the magnitude of expiratory effort. In contrast, the study of infectious episodes revealed a significant reduction of hospital admissions in pre diabetic treated patients.

Conclusion

Overall, our study focuses on the importance of glycemic monitoring during the early stages of CF disease and on the advantage of insulin treatment in the early stages of glucose alteration .

References

Spoonhower KA, Davis PB., Epidemiology of Cystic Fibrosis, Clin Chest Med 2016 Mar;37(1):1-8. DOI: 10.1016/j.ccm.2015.10.002.

Fitz Simmons SC. The changing epidemiology of cystic fibrosis. J Pediatr. 1993 Jan;122(1):1-9. DOI: 10.1016/s0022-3476(05)83478-x.

Lanng S, Hansen A, Thorsteinsson B, Nerup J, Koch C. Glucose tolerance in patients with cystic fibrosis: five-year prospective study. BMJ. 1995 Sep 9;311(7006):655-9. DOI: 10.1136/bmj.311.7006.655.

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 Sep;32(9):1626-31. DOI: 10.2337/dc09-0586.

O'Sullivan BP, Freedman SD.Cystic fibrosis. Lancet. 2009 May 30;373(9678):1891-904. DOI: 10.1016/S0140-6736(09)60327-5.

Iannucci A, Mukai K, Johnson D, Burke B. Endocrine pancreas in cystic fibrosis: an immunohistochemical study. HumPathol. 1984 Mar;15(3):278-84. DOI: 10.1016/s0046-8177(84)80191-4.

Schwarzenberg SJ, Thomas W, Olsen TW et al. Microvascular complications in cystic fibrosis-related diabetes. Diabetes Care. 2007 May;30(5):1056-61. DOI: 10.2337/dc06-1576..

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 Sep;162(3 Pt 1):891-5. DOI: 10.1164/ajrccm.162.3.9904075.

O'Riordan SM, Robinson PD, Donaghue KC, Moran A; ISPAD Clinical Practice Consensus. Management of cystic fibrosis-related diabetes.Pediatr Diabetes. 2008 Jul 28;9(4 Pt 1):338-44. DOI: 10.1111/j.1399-5448.2008.00437.x.

Hameed S1, Jaffé A, Verge CF. Cystic fibrosis related diabetes (CFRD)--the end stage of progressive insulin deficiency. Pediatr Pulmonol. 2011 Aug;46(8):747-60. DOI: 10.1002/ppul.21495.

Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020 -American Diabetes Association-Diabetes Care 2020 Jan; 43(1 Suppl): S14-S31.

Mozzillo E, Raia V, Fattorusso V et al. Glucose derangements in very young children with cystic fibrosis and pancreatic insufficiency. Diabetes Care 2012;35:e78 doi: 10.2337/dc12-0459

Kerem E, Corey M, Kerem BS, Rommens J, Markiewicz D, Levison H,et al..The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med. 1990 Nov 29;323(22):1517-22. DOI: 10.1056/NEJM199011293232203.

Li L, Somerset S. Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy. Dig Liver Dis. 2014 Oct;46(10):865-74. doi: 10.1016/j.dld.2014.06.011. Epub 2014 Jul 19. PMID: 25053610.

Pencharz, P. B., and P. R. Durie. “Pathogenesis of Malnutrition in Cystic Fibrosis, and Its Treatment.” Clinical Nutrition (Edinburgh, Scotland) 19, no. 6 (December 2000): 387–94. doi:10.1054/clnu.1999.0079.

Hirche TO, Knoop C, Hebestreit H, Shimmin D, Solé A, Elborn JS et al. TO; ECORN-CF Study Group. Practical guidelines: lung transplantation in patients with cystic fibrosis. Pulm Med. 2014;2014:621342. DOI: 10.1155/2014/621342. Epub 2014 Mar 30. Erratum in: Pulm Med. 2015;2015:698460.

Snell GI, Bennetts K, Bartolo J, Levvey B, Griffiths A, Williams T, et al. M. Body mass index as a predictor of survival in adults with cystic fibrosis referred for lung transplantation. J Heart Lung Transplant. 1998 Nov;17(11):1097-103.

Lederer DJ, Wilt JS, D'Ovidio F, Bacchetta MD, Shah L, Ravichandran S,et al. . Obesity and underweight are associated with an increased risk of death after lung transplantation. Am J Respir Crit Care Med. 2009 Nov 1;180(9):887-95. DOI: 10.1164/rccm.200903-0425OC.

Moran A, Pekow P, Grover P, Zorn M, Slovis B, Pilewski J et al. ; Cystic Fibrosis Related Diabetes Therapy Study Group. Insulin therapy to improve BMI in cystic fibrosis-related diabetes without fasting hyperglycemia: results of the cystic fibrosis-related diabetes therapy trial. Diabetes Care. 2009 Oct;32(10):1783-8. DOI: 10.2337/dc09-0585.

Pitocco D, Fuso L, Conte EG, Zaccardi F, Condoluci C, Scavone G et al.The diabetic lung--a new target organ?Rev Diabet Stud. 2012 Spring;9(1):23-35. doi: 10.1900/RDS.2012.9.23.

Wood DM, Brennan AL, Philips BJ, Baker EH. Effect of hyperglycemia on glucose concentration of human nasal secretions. Clin Sci (Lond). 2004 May;106(5):527-33. DOI: 10.1042/CS20030333.

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 Apr;6(2):101-9. DOI: 10.1016/j.jcf.2006.03.009.

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 Jan 1;306(1):L43-9. DOI: 10.1152/ajplung.00224.2013. Epub 2013 Oct 4.

Lanng S, Thorsteinsson B, Nerup J, Koch C. Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections. Acta Paediatr. 1994 Aug;83(8):849-53. DOI: 10.1111/j.1651-2227.1994.tb13156.x.

Bizzarri C, Lucidi V, Ciampalini P, Bella S, Russo B, Cappa M.Clinical effects of early treatment with insulin glargine in patients with cystic fibrosis and impaired glucose tolerance. J Endocrinol Invest. 2006 Mar;29(3):RC1-4. DOI: 10.1007/BF03345538.

Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G et al. ; CFRD Guidelines Committee. 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 Dec;33(12):2697-708. DOI: 10.2337/dc10-1768.

Tofé S, Moreno JC, Máiz L, Alonso M, Escobar H, Barrio R. Insulin- secretion abnormalities and clinical deterioration related to im- paired glucose tolerance in cystic fibrosis. Eur J Endocrinol 2005, 152: 241-7.