β-cell Function and Insulin Sensitivity in Patients With Cystic Fibrosis
NCT ID: NCT04379726
Last Updated: 2020-05-07
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
150 participants
Study Classification
OBSERVATIONAL
Study Start Date
2020-07-01
Study Completion Date
2023-09-01
Brief Summary
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Cystic fibrosis is a genetic disorder caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to pulmonary infections, sinus disease, pancreatic insufficiency, hepatobiliary disease and male infertility, with respiratory failure being the primary cause of death. Cystic Fibrosis Related Diabetes (CFRD) in one of the most common complication of cystic fibrosis (CF) and it's associated with a worse respiratory and nutritional state, with a negative impact on life expectancy. It differs from type 1 diabetes and type 2 diabetes for particular characteristics making this disease a separated clinical entity.
To date, there is a lack of evidence on many aspects concerning this disease:
* the pathophysiology of the disease: decreased insulin secretion has historically been seen has the major trigger for CFRD, but data about this mechanism are scarce and conflicting. Moreover, the role of insulin-resistance seems to be not consistent, but pulmonary exacerbations are very common and, in this setting, insulin sensitivity can worsen significantly.
* the relationship between its development and particular genetic settings: certain CFTR genotypes are known to be most related to the risk of diabetes, and only few susceptibility genes for type 2 diabetes have been evaluated as potential predisposing factors for CFRD.
* the relationship between the therapeutic optimization and its impact on metabolic status and lung function: CFRD is known to be associated with worse clinical outcomes, reflected in more frequent clinical exacerbations, greater reduction in lung function, poorer nutritional status and decreased survival. It has also been demonstrated that insulin therapy can improve pulmonary function, increase body weight and reduce lung exacerbations. However, no study on the clinical impact of the optimization of insulin therapy on pulmonary outcomes and life expectancy are available in this population.
* finally, no data about potential predisposing pre-transplant risk factors for development of post-transplant DM are available
For this reason, the investigators have structured a study with the aim to:
* characterize the pathophysiological process leading to CFRD, with assessment of the relative contribution of the insulin resistance and the β-cellular secretion impairment
* define the prevalence of CFRD in relation to the mutations of the CFTR gene and to the presence of candidate genes for the development of type 2 diabetes
* perform a proteomic analysis to identify potential proteomic biomarkers among CFRD patients
* evaluate the body composition, muscle performance and respiratory outcomes in patients on insulin therapy, before and after therapeutic optimization, in a follow-up period of 24 months.
* identify eventual predisposing factors for the development of post-transplant diabetes in subjects without pre-transplant CFRD.
To date, there is a lack of evidence on many aspects concerning this disease:
* the pathophysiology of the disease: decreased insulin secretion has historically been seen has the major trigger for CFRD, but data about this mechanism are scarce and conflicting. Moreover, the role of insulin-resistance seems to be not consistent, but pulmonary exacerbations are very common and, in this setting, insulin sensitivity can worsen significantly.
* the relationship between its development and particular genetic settings: certain CFTR genotypes are known to be most related to the risk of diabetes, and only few susceptibility genes for type 2 diabetes have been evaluated as potential predisposing factors for CFRD.
* the relationship between the therapeutic optimization and its impact on metabolic status and lung function: CFRD is known to be associated with worse clinical outcomes, reflected in more frequent clinical exacerbations, greater reduction in lung function, poorer nutritional status and decreased survival. It has also been demonstrated that insulin therapy can improve pulmonary function, increase body weight and reduce lung exacerbations. However, no study on the clinical impact of the optimization of insulin therapy on pulmonary outcomes and life expectancy are available in this population.
* finally, no data about potential predisposing pre-transplant risk factors for development of post-transplant DM are available
For this reason, the investigators have structured a study with the aim to:
* characterize the pathophysiological process leading to CFRD, with assessment of the relative contribution of the insulin resistance and the β-cellular secretion impairment
* define the prevalence of CFRD in relation to the mutations of the CFTR gene and to the presence of candidate genes for the development of type 2 diabetes
* perform a proteomic analysis to identify potential proteomic biomarkers among CFRD patients
* evaluate the body composition, muscle performance and respiratory outcomes in patients on insulin therapy, before and after therapeutic optimization, in a follow-up period of 24 months.
* identify eventual predisposing factors for the development of post-transplant diabetes in subjects without pre-transplant CFRD.
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Detailed Description
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The study aims are:
* Task 1: pathophysiological characterization of CFRD with assessment of the relative contribution of the insulin resistance and the β-cellular secretion impairment through the use of a Minimum Model applied to OGTT for the evaluation of insulin sensitivity and secretion
* Task 2:
2a) determination of the prevalence of CFRD in relation to the mutations of the CFTR gene (presence of mutations with residual function of the CFTR protein) 2b) determination of the prevalence of CFRD in relation to the presence of candidate genes for the devel-opment of type 2 diabetes (NOTCH2, BCL11A, THADA, IGFBP-2, PPARG, ADAMTS9, CDKAL1, VEFGA, JAZF1, CDKN2A / 2B, HHEX, CDC123 / CAMK1D, TCF7L2, KCNJ11, DCD, TSPAN8 / LGR5, FTO, WFS1, SLC30A8 and INS).
2c) determination of variations in the proteomic analysis of CFRD patients compared to CF without DM and a control group of healthy individuals.
* Task 3: evaluation of the effect of the therapeutic optimization of glycometabolic control on body composition and respiratory outcomes in patients on insulin therapy, in a follow-up period of 24 months.
* Task 4: identification of predisposing factors for the development of post-transplant diabetes in subjects without CFRD.
METHODS:
All CF patients currently followed at the Unit of Pulmonology of our Center (250 subjects) will be considered eligible for the study.
Total duration of the study: 156 weeks (3 years).
The enrolled patients will be divided into two groups:
GROUP 1: subjects with a negative history for CFRD or with a CFRD diagnosis that does not require insulin therapy GROUP 2: subjects suffering from CFRD in insulin therapy
Protocol 1: Group 1; metabolic and anthropometric evaluation and assessment of insulin sensitivity / secretion.
Protocol 2: Group 1 and Group 2; genetic evaluation / proteomic evaluation Protocol 3: Group 2; pre- and post-intervention metabolic, anthropometric and nutritional assessment.
Protocol 4: Group 1 patients without CFRD undergoing lung transplantation (10); genetic, metabolic, an-thropometric and pre-and post-transplant assessment of insulin sensitivity / secretion.
Patients will undergo a:
1. METABOLIC EVALUATION: a venous sampling will be performed for blood glucose, HbA1c, total cholesterol, HDL, triglycerides, blood count, albumin, total proteins, pseudocholinesterase, AST, ALT, GGT, ALP, 25OHvitD
2. GENETIC EVALUATION: the investigators will evaluate the specific genetic mutation of the CFTR gene and the presence of gene variants related to the development of DM2 (NOTCH2, BCL11A, THADA, IGFBP-2, PPARG, ADAMTS9, CDKAL1, VEFGA, JAZF1, CDKN2A / 2B, HHEX, CDC123 / CAMK1D, TCF7L2, KCNJ11, DCD, TSPAN8 / LGR5, FTO, WFS1, SLC30A8 and INS)
3. PROTEOMIC EVALUATION: the investigators will perform a Mass Spectrometry to identify variations in the protein pattern expression in CFRD patients if compared to CF patients without DM and healthy control individuals. The list of analyzed protein is available in supplemental data 2.
4. ANTROPOMETRIC EVALUATION. the anthropometric evaluation will be performed with objective exami-nation (Body Mass Index - BMI, waist circumference - CV and hip circumference - CF) , DEXA total body and bioimpedentiometry
5. DYNAMIC EVALUATION OF INSULIN SENSITIVITY AND β CELL SECRETION. Patients will undergo a 5-hours OGTT with serial blood samples and with the application of a Mathematical Model adapted ad hoc (Appendix 1 for a detailed description of the model), in order to quantify the contribution of insulin resistance and β-cell secretion to the development of CFRD
6. PULMONARY EVALUATION. According to clinical practice, patients will be subjected to respiratory function tests with the calculation of FEV1 (absolute and percentage), exacerbation rate, rate of severe exacerbation (need of hospitalization), patient-reported outcomes (PROs) obtained from the sCF-quality of life questionnaire, which will be provided to patients in paper form.
SAMPLE SIZE AND STATISTICAL ANALYSIS:
Referring to the primary objective of the project, the observational nature of the study and the absence of evidence about the topic make a precise evaluation of the power of the study a difficult issue. However, considering the number of patients available and followed by our Center (n = 136), it has been calculated that the present study will have the power of 80% and an alpha level equal to 5% to show a significant reduction of at least 25% in the 1st phase secretion in the group of diabetics if compared to the non-diabetic group (assuming a mean value in non-diabetics of 1500 (aggiungere udm) and a SD of 500 (udm) (Pass v. 11 NCSS software, LCC, Kaysville, Utah, USA).
A series of descriptive analyzes will be performed: the continuous variables will be presented as averages and standard deviations or median with interquartile ranges, depending on the distribution. Frequency distributions will be presented as numbers and percentages. Data will also be presented graphically with histograms and "Box-and-Whisker" plots in order to evaluate potential anomalous values, allowing a further data-check phase in order to have reliable data for subsequent analyzes. Differences between the groups will be analyzed using parametric tests (t-test or ANOVA) without repeated tests or repeated tests, depending on the task of the project. If the normality of the distributions were violated (normal test based on the Shapiro-Wilk statistics), non-parametric technical correspondents will be used. Categorical data will be compared using contingency tables through the Chi-square test or Fisher's exact test, where appropriate. All tests will be two-tailed and p-values less than 5% will be considered statistically significant.
A series of descriptive analyzes will be performed: the continuous variables will be presented as averages and standard or median deviations with interquartile ranges, depending on the distribution. Frequency distributions will be presented as numbers and percentages. The data will also be presented graphically through histograms and "Box-and-Whisker" plots in order to evaluate potential anomalous values that will allow a further data-check phase in order to have valid data for subsequent analyzes. The differences between the groups will be analyzed using parametric techniques (t-test or ANOVA) without repeated tests or with repeated tests, depending on the task of the project. If the normality of the distributions was violated (normality test based on the Shapiro-Wilk statistics), corresponding non-parametric techniques will be used. Categorical data will be compared using contingency tables through the Chi-square test or Fisher's exact test, where appropriate. All tests will be two-tailed and a p-values less than 5% will be considered statistically significant.
* Task 1: pathophysiological characterization of CFRD with assessment of the relative contribution of the insulin resistance and the β-cellular secretion impairment through the use of a Minimum Model applied to OGTT for the evaluation of insulin sensitivity and secretion
* Task 2:
2a) determination of the prevalence of CFRD in relation to the mutations of the CFTR gene (presence of mutations with residual function of the CFTR protein) 2b) determination of the prevalence of CFRD in relation to the presence of candidate genes for the devel-opment of type 2 diabetes (NOTCH2, BCL11A, THADA, IGFBP-2, PPARG, ADAMTS9, CDKAL1, VEFGA, JAZF1, CDKN2A / 2B, HHEX, CDC123 / CAMK1D, TCF7L2, KCNJ11, DCD, TSPAN8 / LGR5, FTO, WFS1, SLC30A8 and INS).
2c) determination of variations in the proteomic analysis of CFRD patients compared to CF without DM and a control group of healthy individuals.
* Task 3: evaluation of the effect of the therapeutic optimization of glycometabolic control on body composition and respiratory outcomes in patients on insulin therapy, in a follow-up period of 24 months.
* Task 4: identification of predisposing factors for the development of post-transplant diabetes in subjects without CFRD.
METHODS:
All CF patients currently followed at the Unit of Pulmonology of our Center (250 subjects) will be considered eligible for the study.
Total duration of the study: 156 weeks (3 years).
The enrolled patients will be divided into two groups:
GROUP 1: subjects with a negative history for CFRD or with a CFRD diagnosis that does not require insulin therapy GROUP 2: subjects suffering from CFRD in insulin therapy
Protocol 1: Group 1; metabolic and anthropometric evaluation and assessment of insulin sensitivity / secretion.
Protocol 2: Group 1 and Group 2; genetic evaluation / proteomic evaluation Protocol 3: Group 2; pre- and post-intervention metabolic, anthropometric and nutritional assessment.
Protocol 4: Group 1 patients without CFRD undergoing lung transplantation (10); genetic, metabolic, an-thropometric and pre-and post-transplant assessment of insulin sensitivity / secretion.
Patients will undergo a:
1. METABOLIC EVALUATION: a venous sampling will be performed for blood glucose, HbA1c, total cholesterol, HDL, triglycerides, blood count, albumin, total proteins, pseudocholinesterase, AST, ALT, GGT, ALP, 25OHvitD
2. GENETIC EVALUATION: the investigators will evaluate the specific genetic mutation of the CFTR gene and the presence of gene variants related to the development of DM2 (NOTCH2, BCL11A, THADA, IGFBP-2, PPARG, ADAMTS9, CDKAL1, VEFGA, JAZF1, CDKN2A / 2B, HHEX, CDC123 / CAMK1D, TCF7L2, KCNJ11, DCD, TSPAN8 / LGR5, FTO, WFS1, SLC30A8 and INS)
3. PROTEOMIC EVALUATION: the investigators will perform a Mass Spectrometry to identify variations in the protein pattern expression in CFRD patients if compared to CF patients without DM and healthy control individuals. The list of analyzed protein is available in supplemental data 2.
4. ANTROPOMETRIC EVALUATION. the anthropometric evaluation will be performed with objective exami-nation (Body Mass Index - BMI, waist circumference - CV and hip circumference - CF) , DEXA total body and bioimpedentiometry
5. DYNAMIC EVALUATION OF INSULIN SENSITIVITY AND β CELL SECRETION. Patients will undergo a 5-hours OGTT with serial blood samples and with the application of a Mathematical Model adapted ad hoc (Appendix 1 for a detailed description of the model), in order to quantify the contribution of insulin resistance and β-cell secretion to the development of CFRD
6. PULMONARY EVALUATION. According to clinical practice, patients will be subjected to respiratory function tests with the calculation of FEV1 (absolute and percentage), exacerbation rate, rate of severe exacerbation (need of hospitalization), patient-reported outcomes (PROs) obtained from the sCF-quality of life questionnaire, which will be provided to patients in paper form.
SAMPLE SIZE AND STATISTICAL ANALYSIS:
Referring to the primary objective of the project, the observational nature of the study and the absence of evidence about the topic make a precise evaluation of the power of the study a difficult issue. However, considering the number of patients available and followed by our Center (n = 136), it has been calculated that the present study will have the power of 80% and an alpha level equal to 5% to show a significant reduction of at least 25% in the 1st phase secretion in the group of diabetics if compared to the non-diabetic group (assuming a mean value in non-diabetics of 1500 (aggiungere udm) and a SD of 500 (udm) (Pass v. 11 NCSS software, LCC, Kaysville, Utah, USA).
A series of descriptive analyzes will be performed: the continuous variables will be presented as averages and standard deviations or median with interquartile ranges, depending on the distribution. Frequency distributions will be presented as numbers and percentages. Data will also be presented graphically with histograms and "Box-and-Whisker" plots in order to evaluate potential anomalous values, allowing a further data-check phase in order to have reliable data for subsequent analyzes. Differences between the groups will be analyzed using parametric tests (t-test or ANOVA) without repeated tests or repeated tests, depending on the task of the project. If the normality of the distributions were violated (normal test based on the Shapiro-Wilk statistics), non-parametric technical correspondents will be used. Categorical data will be compared using contingency tables through the Chi-square test or Fisher's exact test, where appropriate. All tests will be two-tailed and p-values less than 5% will be considered statistically significant.
A series of descriptive analyzes will be performed: the continuous variables will be presented as averages and standard or median deviations with interquartile ranges, depending on the distribution. Frequency distributions will be presented as numbers and percentages. The data will also be presented graphically through histograms and "Box-and-Whisker" plots in order to evaluate potential anomalous values that will allow a further data-check phase in order to have valid data for subsequent analyzes. The differences between the groups will be analyzed using parametric techniques (t-test or ANOVA) without repeated tests or with repeated tests, depending on the task of the project. If the normality of the distributions was violated (normality test based on the Shapiro-Wilk statistics), corresponding non-parametric techniques will be used. Categorical data will be compared using contingency tables through the Chi-square test or Fisher's exact test, where appropriate. All tests will be two-tailed and a p-values less than 5% will be considered statistically significant.
Conditions
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Cystic Fibrosis-related Diabetes
Study Design
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Observational Model Type
CASE_CONTROL
Study Time Perspective
PROSPECTIVE
Study Groups
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patients with CFRD
Patients with diagnosis of CFRD, after OGTT
therapeutic optimization
Intervention Type
BEHAVIORAL
patients with diagnosis of CFRD will undergo the gold standard treatment for the disease (insulin therapy)
patients without CFRD
Patients without diagnosis of CFRD, after OGTT
No interventions assigned to this group
Interventions
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therapeutic optimization
patients with diagnosis of CFRD will undergo the gold standard treatment for the disease (insulin therapy)
Intervention Type
BEHAVIORAL
Eligibility Criteria
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Inclusion Criteria
* written informed
* diagnosis of cystic fibrosis
* diagnosis of cystic fibrosis
Exclusion Criteria
* celiac disease
* pregnancy
* diagnosis of T1DM
* pregnancy
* diagnosis of T1DM
Minimum Eligible Age
18 Years
Maximum Eligible Age
45 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
OTHER
Sponsor Role
lead
Responsible Party
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Emanuela Orsi
Head of Diabetology
Responsibility Role
PRINCIPAL_INVESTIGATOR
Central Contacts
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References
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MacKenzie T, Gifford AH, Sabadosa KA, Quinton HB, Knapp EA, Goss CH, Marshall BC. Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry. Ann Intern Med. 2014 Aug 19;161(4):233-41. doi: 10.7326/M13-0636.
Reference Type
RESULT
Yoon JC. Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis-Related Diabetes. J Endocr Soc. 2017 Oct 30;1(11):1386-1400. doi: 10.1210/js.2017-00362. eCollection 2017 Nov 1.
Reference Type
RESULT
Haardt M, Benharouga M, Lechardeur D, Kartner N, Lukacs GL. C-terminal truncations destabilize the cystic fibrosis transmembrane conductance regulator without impairing its biogenesis. A novel class of mutation. J Biol Chem. 1999 Jul 30;274(31):21873-7. doi: 10.1074/jbc.274.31.21873.
Reference Type
RESULT
Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. 2005 May 12;352(19):1992-2001. doi: 10.1056/NEJMra043184. No abstract available.
Reference Type
RESULT
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. Epub 2009 Jun 19.
Reference Type
RESULT
Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ. Epidemiology of cystic fibrosis-related diabetes. J Pediatr. 2005 May;146(5):681-7. doi: 10.1016/j.jpeds.2004.12.039.
Reference Type
RESULT
Blackman SM, Tangpricha V. Endocrine Disorders in Cystic Fibrosis. Pediatr Clin North Am. 2016 Aug;63(4):699-708. doi: 10.1016/j.pcl.2016.04.009.
Reference Type
RESULT
Blackman SM, Commander CW, Watson C, Arcara KM, Strug LJ, Stonebraker JR, Wright FA, Rommens JM, Sun L, Pace RG, Norris SA, Durie PR, Drumm ML, Knowles MR, Cutting GR. Genetic modifiers of cystic fibrosis-related diabetes. Diabetes. 2013 Oct;62(10):3627-35. doi: 10.2337/db13-0510. Epub 2013 May 13.
Reference Type
RESULT
Lewis C, Blackman SM, Nelson A, Oberdorfer E, Wells D, Dunitz J, Thomas W, Moran A. Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex. Am J Respir Crit Care Med. 2015 Jan 15;191(2):194-200. doi: 10.1164/rccm.201403-0576OC.
Reference Type
RESULT
Adler AI, Shine BS, Chamnan P, Haworth CS, Bilton D. Genetic determinants and epidemiology of cystic fibrosis-related diabetes: results from a British cohort of children and adults. Diabetes Care. 2008 Sep;31(9):1789-94. doi: 10.2337/dc08-0466. Epub 2008 Jun 5.
Reference Type
RESULT
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.
Reference Type
RESULT
Schaedel C, de Monestrol I, Hjelte L, Johannesson M, Kornfalt R, Lindblad A, Strandvik B, Wahlgren L, Holmberg L. Predictors of deterioration of lung function in cystic fibrosis. Pediatr Pulmonol. 2002 Jun;33(6):483-91. doi: 10.1002/ppul.10100.
Reference Type
RESULT
Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, Robinson KA, Sabadosa KA, Stecenko A, Slovis B; 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. No abstract available.
Reference Type
RESULT
Smyth AR, Bell SC, Bojcin S, Bryon M, Duff A, Flume P, Kashirskaya N, Munck A, Ratjen F, Schwarzenberg SJ, Sermet-Gaudelus I, Southern KW, Taccetti G, Ullrich G, Wolfe S; European Cystic Fibrosis Society. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros. 2014 May;13 Suppl 1:S23-42. doi: 10.1016/j.jcf.2014.03.010.
Reference Type
RESULT
Lanng S, Thorsteinsson B, Roder ME, Nerup J, Koch C. Insulin sensitivity and insulin clearance in cystic fibrosis patients with normal and diabetic glucose tolerance. Clin Endocrinol (Oxf). 1994 Aug;41(2):217-23. doi: 10.1111/j.1365-2265.1994.tb02533.x.
Reference Type
RESULT
Kelly A, Moran A. Update on cystic fibrosis-related diabetes. J Cyst Fibros. 2013 Jul;12(4):318-31. doi: 10.1016/j.jcf.2013.02.008. Epub 2013 Apr 3.
Reference Type
RESULT
Moran A, Diem P, Klein DJ, Levitt MD, Robertson RP. Pancreatic endocrine function in cystic fibrosis. J Pediatr. 1991 May;118(5):715-23. doi: 10.1016/s0022-3476(05)80032-0.
Reference Type
RESULT
Sheikh S, Gudipaty L, De Leon DD, Hadjiliadis D, Kubrak C, Rosenfeld NK, Nyirjesy SC, Peleckis AJ, Malik S, Stefanovski D, Cuchel M, Rubenstein RC, Kelly A, Rickels MR. Reduced beta-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance. Diabetes. 2017 Jan;66(1):134-144. doi: 10.2337/db16-0394. Epub 2016 Aug 5.
Reference Type
RESULT
Moran A, Doherty L, Wang X, Thomas W. Abnormal glucose metabolism in cystic fibrosis. J Pediatr. 1998 Jul;133(1):10-17. doi: 10.1016/s0022-3476(98)70171-4. No abstract available.
Reference Type
RESULT
Ode KL, Moran A. New insights into cystic fibrosis-related diabetes in children. Lancet Diabetes Endocrinol. 2013 Sep;1(1):52-8. doi: 10.1016/S2213-8587(13)70015-9. Epub 2013 May 23.
Reference Type
RESULT
Koivula FNM, McClenaghan NH, Harper AGS, Kelly C. Islet-intrinsic effects of CFTR mutation. Diabetologia. 2016 Jul;59(7):1350-1355. doi: 10.1007/s00125-016-3936-1. Epub 2016 Mar 31.
Reference Type
RESULT
Guo JH, Chen H, Ruan YC, Zhang XL, Zhang XH, Fok KL, Tsang LL, Yu MK, Huang WQ, Sun X, Chung YW, Jiang X, Sohma Y, Chan HC. Glucose-induced electrical activities and insulin secretion in pancreatic islet beta-cells are modulated by CFTR. Nat Commun. 2014 Jul 15;5:4420. doi: 10.1038/ncomms5420.
Reference Type
RESULT
Ali BR. Is cystic fibrosis-related diabetes an apoptotic consequence of ER stress in pancreatic cells? Med Hypotheses. 2009 Jan;72(1):55-7. doi: 10.1016/j.mehy.2008.07.058. Epub 2008 Oct 11.
Reference Type
RESULT
Hudson VM. Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation. Free Radic Biol Med. 2001 Jun 15;30(12):1440-61. doi: 10.1016/s0891-5849(01)00530-5.
Reference Type
RESULT
Ntimbane T, Comte B, Mailhot G, Berthiaume Y, Poitout V, Prentki M, Rabasa-Lhoret R, Levy E. Cystic fibrosis-related diabetes: from CFTR dysfunction to oxidative stress. Clin Biochem Rev. 2009 Nov;30(4):153-77.
Reference Type
RESULT
Edlund A, Esguerra JL, Wendt A, Flodstrom-Tullberg M, Eliasson L. CFTR and Anoctamin 1 (ANO1) contribute to cAMP amplified exocytosis and insulin secretion in human and murine pancreatic beta-cells. BMC Med. 2014 May 28;12:87. doi: 10.1186/1741-7015-12-87.
Reference Type
RESULT
Edlund A, Pedersen MG, Lindqvist A, Wierup N, Flodstrom-Tullberg M, Eliasson L. CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells. Sci Rep. 2017 Mar 7;7(1):90. doi: 10.1038/s41598-017-00098-8.
Reference Type
RESULT
Sun X, Yi Y, Xie W, Liang B, Winter MC, He N, Liu X, Luo M, Yang Y, Ode KL, Uc A, Norris AW, Engelhardt JF. CFTR Influences Beta Cell Function and Insulin Secretion Through Non-Cell Autonomous Exocrine-Derived Factors. Endocrinology. 2017 Oct 1;158(10):3325-3338. doi: 10.1210/en.2017-00187.
Reference Type
RESULT
Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017 Feb;181S:S4-S15.e1. doi: 10.1016/j.jpeds.2016.09.064.
Reference Type
RESULT
Moran A, Pyzdrowski KL, Weinreb J, Kahn BB, Smith SA, Adams KS, Seaquist ER. Insulin sensitivity in cystic fibrosis. Diabetes. 1994 Aug;43(8):1020-6. doi: 10.2337/diab.43.8.1020.
Reference Type
RESULT
Austin A, Kalhan SC, Orenstein D, Nixon P, Arslanian S. Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis. J Clin Endocrinol Metab. 1994 Jul;79(1):80-5. doi: 10.1210/jcem.79.1.8027259.
Reference Type
RESULT
American Diabetes Association. 1. Improving Care and Promoting Health in Populations: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1):S7-S13. doi: 10.2337/dc20-S001.
Reference Type
RESULT
Moran A, Pekow P, Grover P, Zorn M, Slovis B, Pilewski J, Tullis E, Liou TG, Allen H; 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. Epub 2009 Jul 10.
Reference Type
RESULT
Dobson L, Hattersley AT, Tiley S, Elworthy S, Oades PJ, Sheldon CD. Clinical improvement in cystic fibrosis with early insulin treatment. Arch Dis Child. 2002 Nov;87(5):430-1. doi: 10.1136/adc.87.5.430. No abstract available.
Reference Type
RESULT
Mozzillo E, Franzese A, Valerio G, Sepe A, De Simone I, Mazzarella G, Ferri P, Raia V. One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangements. Pediatr Diabetes. 2009 May;10(3):162-7. doi: 10.1111/j.1399-5448.2008.00451.x. Epub 2009 Jan 14.
Reference Type
RESULT
Grancini V, Trombetta M, Lunati ME, Zimbalatti D, Boselli ML, Gatti S, Donato MF, Resi V, D'Ambrosio R, Aghemo A, Pugliese G, Bonadonna RC, Orsi E. Contribution of beta-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease. J Hepatol. 2015 Dec;63(6):1484-90. doi: 10.1016/j.jhep.2015.08.011. Epub 2015 Aug 20.
Reference Type
RESULT
Bonadonna RC, Heise T, Arbet-Engels C, Kapitza C, Avogaro A, Grimsby J, Zhi J, Grippo JF, Balena R. Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab. 2010 Nov;95(11):5028-36. doi: 10.1210/jc.2010-1041. Epub 2010 Aug 25.
Reference Type
RESULT
Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care. 2001 Mar;24(3):539-48. doi: 10.2337/diacare.24.3.539.
Reference Type
RESULT
Cobelli C, Toffolo GM, Dalla Man C, Campioni M, Denti P, Caumo A, Butler P, Rizza R. Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E1-E15. doi: 10.1152/ajpendo.00421.2006. Epub 2007 Mar 6.
Reference Type
RESULT
Mari A, Camastra S, Toschi E, Giancaterini A, Gastaldelli A, Mingrone G, Ferrannini E. A model for glucose control of insulin secretion during 24 h of free living. Diabetes. 2001 Feb;50 Suppl 1:S164-8. doi: 10.2337/diabetes.50.2007.s164.
Reference Type
RESULT
Grancini V, Alicandro G, Porcaro LL, Zazzeron L, Gramegna A, Morlacchi LC, Rossetti V, Gaglio A, Resi V, Dacco V, Blasi F, Orsi E. Effects of insulin therapy optimization with sensor augmented pumps on glycemic control and body composition in people with cystic fibrosis-related diabetes. Front Endocrinol (Lausanne). 2023 Aug 31;14:1228153. doi: 10.3389/fendo.2023.1228153. eCollection 2023.
Reference Type
DERIVED
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http://cftr2.org
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Other Identifiers
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FCMilano
Identifier Type: -
Identifier Source: org_study_id
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