ANDREA FOPPIANI, FABIANA CICIRIELLO, FEDERICO ALGHISI, VINCENZINA LUCIDI, FEDERICA SILEO, MARIA CRISTINA LUCANTO, FABIOLA CORTI, CARLA COLOMBO, ALBERTO BATTEZZATI
{"title":"1552-P：具有残余 CFTR 功能的突变与囊性纤维化患者更好的葡萄糖耐受性和胰岛素分泌有关","authors":"ANDREA FOPPIANI, FABIANA CICIRIELLO, FEDERICO ALGHISI, VINCENZINA LUCIDI, FEDERICA SILEO, MARIA CRISTINA LUCANTO, FABIOLA CORTI, CARLA COLOMBO, ALBERTO BATTEZZATI","doi":"10.2337/db24-1552-p","DOIUrl":null,"url":null,"abstract":"People with Cystic Fibrosis (pwCF) exhibit a defect of insulin secretion[1], potentially leading to Cystic Fibrosis Related Diabetes. Little information exists about the molecular mechanism that links the defect of insulin secretion to the CF-causing variants of the CFTR gene[2,3]. We sought to describe the relationship between the CFTR function and β-cell function in pwCF. We studied 341 patients (193 (57%) females, 271 (79%) pancreatic insufficient, median (IQR) age 19 (15, 24) years) with the oral glucose tolerance test (OGTT), sampling glucose, insulin, and C-peptide before and every 30 minutes over the 2 hour OGTT, modeling β-cell function expressed by the β-cell glucose sensitivity[4]. Each patient was characterized by either having at least one allele with a residual function mutation (group 1, 85 (25%)), or a minimal function mutation on both alleles (group 2, 255 (75%) ). After adjusting for sex, pancreatic insufficiency (PI), and age, patients in group 1 displayed better glucose tolerance at all OGTT timepoint (all p=<0.05), and better β-cell glucose sensitivity (22 pmol×min⁻¹×m⁻²×mM⁻¹; 95% CI 9.6, 34; p=<0.001).Within the whole sample, 162 patients (82 (51%) females, 136 (84%) of group 2, 139 (86%) pancreatic insufficient, median (IQR) age 20 (15, 25) years) carried variants on both alleles that had been tested for chloride conductance in the Fischer Rat Thyroid cell line (http://cftr2.org). The mean chloride conductance of the most functional allele was positively related to β-cell glucose sensitivity (0.96; 95% CI 0.13, 1.8; p=0.025), with no PI interaction (interaction term -0.63; 95% CI -3.7, 2.4; p=0.7), and adjusting for differences in sex and age. In conclusion, we have shown that CFTR function is quantitatively related to β-cell function in pwCF. Even though exocrine PI is associated with worse β-cell function, the association of CFTR residual function and β-cell glucose sensitivity is not necessarily mediated by exocrine PI. Disclosure A. Foppiani: None. F. Ciciriello: None. F. Alghisi: None. V. Lucidi: None. F. Sileo: None. M. Lucanto: None. F. Corti: None. C. Colombo: None. A. Battezzati: None. Funding Cystic Fibrosis Research Foundation FFC#16/2005, FFC#21/2013, FFC#20/2016, and FFC#24/2019","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"1552-P: Mutations with Residual CFTR Function Are Associated to Better Glucose Tolerance and Insulin Secretion in Patients with Cystic Fibrosis\",\"authors\":\"ANDREA FOPPIANI, FABIANA CICIRIELLO, FEDERICO ALGHISI, VINCENZINA LUCIDI, FEDERICA SILEO, MARIA CRISTINA LUCANTO, FABIOLA CORTI, CARLA COLOMBO, ALBERTO BATTEZZATI\",\"doi\":\"10.2337/db24-1552-p\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"People with Cystic Fibrosis (pwCF) exhibit a defect of insulin secretion[1], potentially leading to Cystic Fibrosis Related Diabetes. Little information exists about the molecular mechanism that links the defect of insulin secretion to the CF-causing variants of the CFTR gene[2,3]. We sought to describe the relationship between the CFTR function and β-cell function in pwCF. We studied 341 patients (193 (57%) females, 271 (79%) pancreatic insufficient, median (IQR) age 19 (15, 24) years) with the oral glucose tolerance test (OGTT), sampling glucose, insulin, and C-peptide before and every 30 minutes over the 2 hour OGTT, modeling β-cell function expressed by the β-cell glucose sensitivity[4]. Each patient was characterized by either having at least one allele with a residual function mutation (group 1, 85 (25%)), or a minimal function mutation on both alleles (group 2, 255 (75%) ). After adjusting for sex, pancreatic insufficiency (PI), and age, patients in group 1 displayed better glucose tolerance at all OGTT timepoint (all p=<0.05), and better β-cell glucose sensitivity (22 pmol×min⁻¹×m⁻²×mM⁻¹; 95% CI 9.6, 34; p=<0.001).Within the whole sample, 162 patients (82 (51%) females, 136 (84%) of group 2, 139 (86%) pancreatic insufficient, median (IQR) age 20 (15, 25) years) carried variants on both alleles that had been tested for chloride conductance in the Fischer Rat Thyroid cell line (http://cftr2.org). The mean chloride conductance of the most functional allele was positively related to β-cell glucose sensitivity (0.96; 95% CI 0.13, 1.8; p=0.025), with no PI interaction (interaction term -0.63; 95% CI -3.7, 2.4; p=0.7), and adjusting for differences in sex and age. In conclusion, we have shown that CFTR function is quantitatively related to β-cell function in pwCF. Even though exocrine PI is associated with worse β-cell function, the association of CFTR residual function and β-cell glucose sensitivity is not necessarily mediated by exocrine PI. Disclosure A. Foppiani: None. F. Ciciriello: None. F. Alghisi: None. V. Lucidi: None. F. Sileo: None. M. Lucanto: None. F. Corti: None. C. Colombo: None. A. Battezzati: None. 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1552-P: Mutations with Residual CFTR Function Are Associated to Better Glucose Tolerance and Insulin Secretion in Patients with Cystic Fibrosis
People with Cystic Fibrosis (pwCF) exhibit a defect of insulin secretion[1], potentially leading to Cystic Fibrosis Related Diabetes. Little information exists about the molecular mechanism that links the defect of insulin secretion to the CF-causing variants of the CFTR gene[2,3]. We sought to describe the relationship between the CFTR function and β-cell function in pwCF. We studied 341 patients (193 (57%) females, 271 (79%) pancreatic insufficient, median (IQR) age 19 (15, 24) years) with the oral glucose tolerance test (OGTT), sampling glucose, insulin, and C-peptide before and every 30 minutes over the 2 hour OGTT, modeling β-cell function expressed by the β-cell glucose sensitivity[4]. Each patient was characterized by either having at least one allele with a residual function mutation (group 1, 85 (25%)), or a minimal function mutation on both alleles (group 2, 255 (75%) ). After adjusting for sex, pancreatic insufficiency (PI), and age, patients in group 1 displayed better glucose tolerance at all OGTT timepoint (all p=<0.05), and better β-cell glucose sensitivity (22 pmol×min⁻¹×m⁻²×mM⁻¹; 95% CI 9.6, 34; p=<0.001).Within the whole sample, 162 patients (82 (51%) females, 136 (84%) of group 2, 139 (86%) pancreatic insufficient, median (IQR) age 20 (15, 25) years) carried variants on both alleles that had been tested for chloride conductance in the Fischer Rat Thyroid cell line (http://cftr2.org). The mean chloride conductance of the most functional allele was positively related to β-cell glucose sensitivity (0.96; 95% CI 0.13, 1.8; p=0.025), with no PI interaction (interaction term -0.63; 95% CI -3.7, 2.4; p=0.7), and adjusting for differences in sex and age. In conclusion, we have shown that CFTR function is quantitatively related to β-cell function in pwCF. Even though exocrine PI is associated with worse β-cell function, the association of CFTR residual function and β-cell glucose sensitivity is not necessarily mediated by exocrine PI. Disclosure A. Foppiani: None. F. Ciciriello: None. F. Alghisi: None. V. Lucidi: None. F. Sileo: None. M. Lucanto: None. F. Corti: None. C. Colombo: None. A. Battezzati: None. Funding Cystic Fibrosis Research Foundation FFC#16/2005, FFC#21/2013, FFC#20/2016, and FFC#24/2019
期刊介绍：
Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes.
However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
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