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Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance

IntroductionPrevious studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympath...

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Published in:BMJ open diabetes research & care 2024-12, Vol.12 (6), p.e004542
Main Authors: Dimova, Rumyana, Chakarova, Nevena, Serdarova, Mina, Marinova, Cvetelina, Popov, Dimitar, Del Prato, Stefano, Tankova, Tsvetalina
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container_start_page e004542
container_title BMJ open diabetes research & care
container_volume 12
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Chakarova, Nevena
Serdarova, Mina
Marinova, Cvetelina
Popov, Dimitar
Del Prato, Stefano
Tankova, Tsvetalina
description IntroductionPrevious studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.Research design and methodsTwenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m2) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m2) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP >233 dB/m.ResultsA CAP >233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A “cut-off” value of 15,620 uIU/mL-1*180 min-1 provided a 75% sensitivity and 75% specificity for CAP >233 dB/m.ConclusionsOur results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.
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We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.Research design and methodsTwenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m2) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m2) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP &gt;233 dB/m.ResultsA CAP &gt;233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A “cut-off” value of 15,620 uIU/mL-1*180 min-1 provided a 75% sensitivity and 75% specificity for CAP &gt;233 dB/m.ConclusionsOur results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.</description><identifier>ISSN: 2052-4897</identifier><identifier>EISSN: 2052-4897</identifier><identifier>DOI: 10.1136/bmjdrc-2024-004542</identifier><identifier>PMID: 39706674</identifier><language>eng</language><publisher>England: American Diabetes Association</publisher><subject>Adult ; Autonomic Function ; Autonomic Nervous System - physiopathology ; Biomarkers - analysis ; Blood Glucose - analysis ; Body Mass Index ; Cardiovascular and Metabolic Risk ; Clinical medicine ; Diabetes ; Female ; Follow-Up Studies ; Glucose ; Glucose Intolerance - physiopathology ; Glucose Tolerance Test ; Humans ; Hyperinsulinemia ; Impaired Glucose Tolerance ; Insulin - metabolism ; Insulin resistance ; Insulin Resistance - physiology ; Insulin Secretion ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - physiology ; Liver diseases ; Male ; Metabolism ; Middle Aged ; Nervous system ; Non-alcoholic Fatty Liver Disease - physiopathology ; Original Research ; Pathogenesis ; Peptides ; Prognosis ; Respiration ; Software ; Statistical analysis ; Variance analysis</subject><ispartof>BMJ open diabetes research &amp; care, 2024-12, Vol.12 (6), p.e004542</ispartof><rights>Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.</rights><rights>2024 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-b3322-7d7639df78f53fb4965331169e5cbf449cdc97a970b305aa2f36a500ba0009343</cites><orcidid>0000-0003-2838-4344 ; 0000-0002-5388-0270</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3147734508/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3147734508?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25751,27922,27923,37010,37011,44588,53789,53791,55348,74896,77430,77456</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39706674$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dimova, Rumyana</creatorcontrib><creatorcontrib>Chakarova, Nevena</creatorcontrib><creatorcontrib>Serdarova, Mina</creatorcontrib><creatorcontrib>Marinova, Cvetelina</creatorcontrib><creatorcontrib>Popov, Dimitar</creatorcontrib><creatorcontrib>Del Prato, Stefano</creatorcontrib><creatorcontrib>Tankova, Tsvetalina</creatorcontrib><title>Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance</title><title>BMJ open diabetes research &amp; care</title><addtitle>BMJ Open Diab Res Care</addtitle><addtitle>BMJ Open Diabetes Res Care</addtitle><description>IntroductionPrevious studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.Research design and methodsTwenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m2) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m2) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP &gt;233 dB/m.ResultsA CAP &gt;233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A “cut-off” value of 15,620 uIU/mL-1*180 min-1 provided a 75% sensitivity and 75% specificity for CAP &gt;233 dB/m.ConclusionsOur results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.</description><subject>Adult</subject><subject>Autonomic Function</subject><subject>Autonomic Nervous System - physiopathology</subject><subject>Biomarkers - analysis</subject><subject>Blood Glucose - analysis</subject><subject>Body Mass Index</subject><subject>Cardiovascular and Metabolic Risk</subject><subject>Clinical medicine</subject><subject>Diabetes</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Glucose</subject><subject>Glucose Intolerance - physiopathology</subject><subject>Glucose Tolerance Test</subject><subject>Humans</subject><subject>Hyperinsulinemia</subject><subject>Impaired Glucose Tolerance</subject><subject>Insulin - metabolism</subject><subject>Insulin resistance</subject><subject>Insulin Resistance - physiology</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Insulin-Secreting Cells - physiology</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Nervous system</subject><subject>Non-alcoholic Fatty Liver Disease - physiopathology</subject><subject>Original Research</subject><subject>Pathogenesis</subject><subject>Peptides</subject><subject>Prognosis</subject><subject>Respiration</subject><subject>Software</subject><subject>Statistical analysis</subject><subject>Variance analysis</subject><issn>2052-4897</issn><issn>2052-4897</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk9v1DAQxSMEolXpF-CALHHh0BTHf-L4hNpCodIiLnC2xo69ZJXYi-1U2m-P05TScuBky_Pm55mnV1WvG3zeNLR9r6ddH01NMGE1xowz8qw6JpiTmnVSPH90P6pOU9phjEtbQzv-sjqiUuC2Fey42l_aDLWx43iG9JyRDxnBnIMP02CQt_E2zAmlQ8p2OkNu9iYPwaMhoWhHyLZHOaCvF9ebj2jwyEIcDyhl2NqEgkPbcTYh2VLKYbQRvLGvqhcOxmRP78-T6sf1p-9XX-rNt883VxebWlNKSC160VLZO9E5Tp1msuWUNk0rLTfaMSZNb6SAsoemmAMQR1vgGGsoi0rK6El1s3L7ADu1j8ME8aACDOruIcStgpgHM1rVQWu6xnWOyI51WkotjHAgpGGaAe8K68PK2s96sr2xPkcYn0CfVvzwU23DrSoDF5fJQnh3T4jh12xTVtOQFtfB22Kwog0TUlAscZG-_Ue6C3P0xas7laCM4wVIVpWJIaVo3cM0DVZLQNQaELUERK0BKU1vHu_x0PInDkVwvgpK899v_0P8Day_xgI</recordid><startdate>20241220</startdate><enddate>20241220</enddate><creator>Dimova, Rumyana</creator><creator>Chakarova, Nevena</creator><creator>Serdarova, Mina</creator><creator>Marinova, Cvetelina</creator><creator>Popov, Dimitar</creator><creator>Del Prato, Stefano</creator><creator>Tankova, Tsvetalina</creator><general>American Diabetes Association</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2838-4344</orcidid><orcidid>https://orcid.org/0000-0002-5388-0270</orcidid></search><sort><creationdate>20241220</creationdate><title>Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance</title><author>Dimova, Rumyana ; Chakarova, Nevena ; Serdarova, Mina ; Marinova, Cvetelina ; Popov, Dimitar ; Del Prato, Stefano ; Tankova, Tsvetalina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b3322-7d7639df78f53fb4965331169e5cbf449cdc97a970b305aa2f36a500ba0009343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Autonomic Function</topic><topic>Autonomic Nervous System - physiopathology</topic><topic>Biomarkers - analysis</topic><topic>Blood Glucose - analysis</topic><topic>Body Mass Index</topic><topic>Cardiovascular and Metabolic Risk</topic><topic>Clinical medicine</topic><topic>Diabetes</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Glucose</topic><topic>Glucose Intolerance - physiopathology</topic><topic>Glucose Tolerance Test</topic><topic>Humans</topic><topic>Hyperinsulinemia</topic><topic>Impaired Glucose Tolerance</topic><topic>Insulin - metabolism</topic><topic>Insulin resistance</topic><topic>Insulin Resistance - physiology</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Insulin-Secreting Cells - physiology</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Nervous system</topic><topic>Non-alcoholic Fatty Liver Disease - physiopathology</topic><topic>Original Research</topic><topic>Pathogenesis</topic><topic>Peptides</topic><topic>Prognosis</topic><topic>Respiration</topic><topic>Software</topic><topic>Statistical analysis</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dimova, Rumyana</creatorcontrib><creatorcontrib>Chakarova, Nevena</creatorcontrib><creatorcontrib>Serdarova, Mina</creatorcontrib><creatorcontrib>Marinova, Cvetelina</creatorcontrib><creatorcontrib>Popov, Dimitar</creatorcontrib><creatorcontrib>Del Prato, Stefano</creatorcontrib><creatorcontrib>Tankova, Tsvetalina</creatorcontrib><collection>British Medical Journal Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; 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care</jtitle><stitle>BMJ Open Diab Res Care</stitle><addtitle>BMJ Open Diabetes Res Care</addtitle><date>2024-12-20</date><risdate>2024</risdate><volume>12</volume><issue>6</issue><spage>e004542</spage><pages>e004542-</pages><issn>2052-4897</issn><eissn>2052-4897</eissn><abstract>IntroductionPrevious studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.Research design and methodsTwenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m2) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m2) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP &gt;233 dB/m.ResultsA CAP &gt;233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A “cut-off” value of 15,620 uIU/mL-1*180 min-1 provided a 75% sensitivity and 75% specificity for CAP &gt;233 dB/m.ConclusionsOur results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.</abstract><cop>England</cop><pub>American Diabetes Association</pub><pmid>39706674</pmid><doi>10.1136/bmjdrc-2024-004542</doi><orcidid>https://orcid.org/0000-0003-2838-4344</orcidid><orcidid>https://orcid.org/0000-0002-5388-0270</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adult
Autonomic Function
Autonomic Nervous System - physiopathology
Biomarkers - analysis
Blood Glucose - analysis
Body Mass Index
Cardiovascular and Metabolic Risk
Clinical medicine
Diabetes
Female
Follow-Up Studies
Glucose
Glucose Intolerance - physiopathology
Glucose Tolerance Test
Humans
Hyperinsulinemia
Impaired Glucose Tolerance
Insulin - metabolism
Insulin resistance
Insulin Resistance - physiology
Insulin Secretion
Insulin-Secreting Cells - metabolism
Insulin-Secreting Cells - physiology
Liver diseases
Male
Metabolism
Middle Aged
Nervous system
Non-alcoholic Fatty Liver Disease - physiopathology
Original Research
Pathogenesis
Peptides
Prognosis
Respiration
Software
Statistical analysis
Variance analysis
title Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance
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