Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function
Abstract Objective We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevat...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2021-04, Vol.106 (4), p.e1793-e1802 |
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| creator | Piona, Claudia Volpi, Sonia Zusi, Chiara Mozzillo, Enza Tosco, Antonella Franzese, Adriana Raia, Valeria Boselli, Maria Linda Trombetta, Maddalena Cipolli, Marco Bonadonna, Riccardo C Maffeis, Claudio |
| description | Abstract
Objective
We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevation of mid-level oral glucose tolerance test (OGTT) glucose values (>140 and |
| doi_str_mv | 10.1210/clinem/dgaa932 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2470900438</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A702425612</galeid><oup_id>10.1210/clinem/dgaa932</oup_id><sourcerecordid>A702425612</sourcerecordid><originalsourceid>FETCH-LOGICAL-c464t-e35f02f9b978896100a19c79b96048220e2123e73d6fbd67c8840a11f613a5bb3</originalsourceid><addsrcrecordid>eNqFkcFrHCEUxqU0NJu01x6L0EtzmEQdZxyPm002DQRSaAK9ieM8F8OMbtU57H9fl922UAL1HXxPfu_jww-hj5RcUkbJlRmdh-lq2Ggta_YGLajkTSWoFG_RghBGKynYj1N0ltILIZTzpn6HTutyaCfEAoW7cTYhAX4KI0TtDeDvWW8gYefxapeyM3jt-hiSS3gZAd8P4LOzDgbc77DGz979nAF_0zlD9DhYfAMWTE779hqyrlYwjng9e5Nd8O_RidVjgg_H-xw9r2-fVl-rh8e7-9XyoTK85bmCurGEWdlL0XWypYRoKo0oc0t4xxgBRlkNoh5a2w-tMF3HC0JtS2vd9H19jr4cdLcxFH8pq8klU5xoD2FOinFBJCG87gr6-R_0JczRF3eKyaYIEiboX2qjR1DO25CjNntRtRSEcVZIVqjLV6hSA0zOBA_WlffXFkz54hTBqm10k447RYnaJ6wOCatjwmXh09Ht3E8w_MF_R1qAiwMQ5u3_xH4BlN2uMA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2956130271</pqid></control><display><type>article</type><title>Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Piona, Claudia ; Volpi, Sonia ; Zusi, Chiara ; Mozzillo, Enza ; Tosco, Antonella ; Franzese, Adriana ; Raia, Valeria ; Boselli, Maria Linda ; Trombetta, Maddalena ; Cipolli, Marco ; Bonadonna, Riccardo C ; Maffeis, Claudio</creator><creatorcontrib>Piona, Claudia ; Volpi, Sonia ; Zusi, Chiara ; Mozzillo, Enza ; Tosco, Antonella ; Franzese, Adriana ; Raia, Valeria ; Boselli, Maria Linda ; Trombetta, Maddalena ; Cipolli, Marco ; Bonadonna, Riccardo C ; Maffeis, Claudio</creatorcontrib><description>Abstract
Objective
We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevation of mid-level oral glucose tolerance test (OGTT) glucose values (>140 and <200 mg/dL), referred to as AGT140.
Methods
A total of 232 CF patients aged 10 to 25 years underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modeling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between glucometabolic variables and 5 glucose tolerance stages (normal glucose tolerance [NGT], AGT140, indeterminate glucose tolerance [INDET], impaired glucose tolerance [IGT], cystic fibrosis–related diabetes CFRD]) was assessed with a general linear model.
Results
Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (P < 0.001), with AGT140 patients significantly differing from NGT (all P < 0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all P < 0.01). Insulin clearance was not significantly associated with glucose tolerance stages (P = 0.162). Each stage of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation.
Conclusions
In CF patients, each of the 5 glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest that AGT140 should be recognized as a distinct glucose tolerance stage and that reconsideration of the grade of glucometabolic deterioration across glucose tolerance stages in CF is warranted.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgaa932</identifier><identifier>PMID: 33331877</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Analysis ; Beta cells ; Cystic fibrosis ; Dextrose ; Diabetes mellitus ; Glucose ; Glucose metabolism ; Glucose tolerance ; Glucose tolerance tests ; Insulin ; Insulin secretion ; Mathematical models ; Pancreatic beta cells ; Physiological aspects</subject><ispartof>The journal of clinical endocrinology and metabolism, 2021-04, Vol.106 (4), p.e1793-e1802</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-e35f02f9b978896100a19c79b96048220e2123e73d6fbd67c8840a11f613a5bb3</citedby><cites>FETCH-LOGICAL-c464t-e35f02f9b978896100a19c79b96048220e2123e73d6fbd67c8840a11f613a5bb3</cites><orcidid>0000-0002-3563-4404</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33331877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piona, Claudia</creatorcontrib><creatorcontrib>Volpi, Sonia</creatorcontrib><creatorcontrib>Zusi, Chiara</creatorcontrib><creatorcontrib>Mozzillo, Enza</creatorcontrib><creatorcontrib>Tosco, Antonella</creatorcontrib><creatorcontrib>Franzese, Adriana</creatorcontrib><creatorcontrib>Raia, Valeria</creatorcontrib><creatorcontrib>Boselli, Maria Linda</creatorcontrib><creatorcontrib>Trombetta, Maddalena</creatorcontrib><creatorcontrib>Cipolli, Marco</creatorcontrib><creatorcontrib>Bonadonna, Riccardo C</creatorcontrib><creatorcontrib>Maffeis, Claudio</creatorcontrib><title>Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Objective
We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevation of mid-level oral glucose tolerance test (OGTT) glucose values (>140 and <200 mg/dL), referred to as AGT140.
Methods
A total of 232 CF patients aged 10 to 25 years underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modeling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between glucometabolic variables and 5 glucose tolerance stages (normal glucose tolerance [NGT], AGT140, indeterminate glucose tolerance [INDET], impaired glucose tolerance [IGT], cystic fibrosis–related diabetes CFRD]) was assessed with a general linear model.
Results
Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (P < 0.001), with AGT140 patients significantly differing from NGT (all P < 0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all P < 0.01). Insulin clearance was not significantly associated with glucose tolerance stages (P = 0.162). Each stage of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation.
Conclusions
In CF patients, each of the 5 glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest that AGT140 should be recognized as a distinct glucose tolerance stage and that reconsideration of the grade of glucometabolic deterioration across glucose tolerance stages in CF is warranted.</description><subject>Analysis</subject><subject>Beta cells</subject><subject>Cystic fibrosis</subject><subject>Dextrose</subject><subject>Diabetes mellitus</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>Glucose tolerance</subject><subject>Glucose tolerance tests</subject><subject>Insulin</subject><subject>Insulin secretion</subject><subject>Mathematical models</subject><subject>Pancreatic beta cells</subject><subject>Physiological aspects</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkcFrHCEUxqU0NJu01x6L0EtzmEQdZxyPm002DQRSaAK9ieM8F8OMbtU57H9fl922UAL1HXxPfu_jww-hj5RcUkbJlRmdh-lq2Ggta_YGLajkTSWoFG_RghBGKynYj1N0ltILIZTzpn6HTutyaCfEAoW7cTYhAX4KI0TtDeDvWW8gYefxapeyM3jt-hiSS3gZAd8P4LOzDgbc77DGz979nAF_0zlD9DhYfAMWTE779hqyrlYwjng9e5Nd8O_RidVjgg_H-xw9r2-fVl-rh8e7-9XyoTK85bmCurGEWdlL0XWypYRoKo0oc0t4xxgBRlkNoh5a2w-tMF3HC0JtS2vd9H19jr4cdLcxFH8pq8klU5xoD2FOinFBJCG87gr6-R_0JczRF3eKyaYIEiboX2qjR1DO25CjNntRtRSEcVZIVqjLV6hSA0zOBA_WlffXFkz54hTBqm10k447RYnaJ6wOCatjwmXh09Ht3E8w_MF_R1qAiwMQ5u3_xH4BlN2uMA</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Piona, Claudia</creator><creator>Volpi, Sonia</creator><creator>Zusi, Chiara</creator><creator>Mozzillo, Enza</creator><creator>Tosco, Antonella</creator><creator>Franzese, Adriana</creator><creator>Raia, Valeria</creator><creator>Boselli, Maria Linda</creator><creator>Trombetta, Maddalena</creator><creator>Cipolli, Marco</creator><creator>Bonadonna, Riccardo C</creator><creator>Maffeis, Claudio</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3563-4404</orcidid></search><sort><creationdate>20210401</creationdate><title>Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function</title><author>Piona, Claudia ; Volpi, Sonia ; Zusi, Chiara ; Mozzillo, Enza ; Tosco, Antonella ; Franzese, Adriana ; Raia, Valeria ; Boselli, Maria Linda ; Trombetta, Maddalena ; Cipolli, Marco ; Bonadonna, Riccardo C ; Maffeis, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-e35f02f9b978896100a19c79b96048220e2123e73d6fbd67c8840a11f613a5bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Analysis</topic><topic>Beta cells</topic><topic>Cystic fibrosis</topic><topic>Dextrose</topic><topic>Diabetes mellitus</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>Glucose tolerance</topic><topic>Glucose tolerance tests</topic><topic>Insulin</topic><topic>Insulin secretion</topic><topic>Mathematical models</topic><topic>Pancreatic beta cells</topic><topic>Physiological aspects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piona, Claudia</creatorcontrib><creatorcontrib>Volpi, Sonia</creatorcontrib><creatorcontrib>Zusi, Chiara</creatorcontrib><creatorcontrib>Mozzillo, Enza</creatorcontrib><creatorcontrib>Tosco, Antonella</creatorcontrib><creatorcontrib>Franzese, Adriana</creatorcontrib><creatorcontrib>Raia, Valeria</creatorcontrib><creatorcontrib>Boselli, Maria Linda</creatorcontrib><creatorcontrib>Trombetta, Maddalena</creatorcontrib><creatorcontrib>Cipolli, Marco</creatorcontrib><creatorcontrib>Bonadonna, Riccardo C</creatorcontrib><creatorcontrib>Maffeis, Claudio</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piona, Claudia</au><au>Volpi, Sonia</au><au>Zusi, Chiara</au><au>Mozzillo, Enza</au><au>Tosco, Antonella</au><au>Franzese, Adriana</au><au>Raia, Valeria</au><au>Boselli, Maria Linda</au><au>Trombetta, Maddalena</au><au>Cipolli, Marco</au><au>Bonadonna, Riccardo C</au><au>Maffeis, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>106</volume><issue>4</issue><spage>e1793</spage><epage>e1802</epage><pages>e1793-e1802</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Objective
We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevation of mid-level oral glucose tolerance test (OGTT) glucose values (>140 and <200 mg/dL), referred to as AGT140.
Methods
A total of 232 CF patients aged 10 to 25 years underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modeling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between glucometabolic variables and 5 glucose tolerance stages (normal glucose tolerance [NGT], AGT140, indeterminate glucose tolerance [INDET], impaired glucose tolerance [IGT], cystic fibrosis–related diabetes CFRD]) was assessed with a general linear model.
Results
Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (P < 0.001), with AGT140 patients significantly differing from NGT (all P < 0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all P < 0.01). Insulin clearance was not significantly associated with glucose tolerance stages (P = 0.162). Each stage of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation.
Conclusions
In CF patients, each of the 5 glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest that AGT140 should be recognized as a distinct glucose tolerance stage and that reconsideration of the grade of glucometabolic deterioration across glucose tolerance stages in CF is warranted.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33331877</pmid><doi>10.1210/clinem/dgaa932</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3563-4404</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 0021-972X 1945-7197 |
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| source | Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Analysis Beta cells Cystic fibrosis Dextrose Diabetes mellitus Glucose Glucose metabolism Glucose tolerance Glucose tolerance tests Insulin Insulin secretion Mathematical models Pancreatic beta cells Physiological aspects |
| title | Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function |
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