Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects
Aim Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity‐induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obes...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2014-03, Vol.16 (3), p.268-272 |
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| creator | Garg, R. Kneen, L. Williams, G. H. Adler, G. K. |
| description | Aim
Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity‐induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo‐controlled, double‐blind, randomized, parallel‐group study (NCT01406015).
Methods
Thirty‐two non‐diabetic, obese subjects [body mass index (BMI) 30 to 45 kg/m2] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation (FMD) of brachial artery and renal plasma perfusion by clearance of para‐aminohippurate (PAH).
Results
There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p |
| doi_str_mv | 10.1111/dom.12224 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3946356</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3059436308</sourcerecordid><originalsourceid>FETCH-LOGICAL-c6084-a91704e23c8d65299a0e07753b45e5aa03f6d3185d85e27a760939c58fbba28c3</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhSNERUthwR9AkdjAIq3fjw0SastQUagQICQ2luPctB4Se7ATaP99zUw7AiTwxpbvd4997qmqJxgd4LIOuzgeYEIIu1ftYSZogykR99dn0iiNyG71MOclQohRJR9Uu4Rhwpmie9XqpO_BTXXs69EHSHaILqbJu-i7OoGD1RRTbcNkL2LwuYCh9iHPgw-lnMuNDQ4K0NUQujhdwuDtUPdzcJNfs3VsIUOd53ZZHsqPqp3eDhke3-771efXJ5-O3jRn54vTo1dnjRNIscZqLBEDQp3qBCdaWwRISk5bxoFbi2gvOooV7xQHIq0USFPtuOrb1hLl6H71cqO7mtsROgdhKubMKvnRpmsTrTd_VoK_NBfxh6G6TJCLIvD8ViDF7zPkyYw-OxgGGyDO2WBFZRmzFqigz_5Cl3FOodgzFHHNqKBI_Y_CTDPMFFesUC82lEsx5wT99ssYmV9pm5K2Wadd2Ke_e9ySd_EW4HAD_PQDXP9byRyfv7uTbDYdJVm42nbY9M0ISSU3X94vjHyLFl8_fDw2jN4Anx_EGA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1494148584</pqid></control><display><type>article</type><title>Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects</title><source>MEDLINE</source><source>Wiley Online Library</source><creator>Garg, R. ; Kneen, L. ; Williams, G. H. ; Adler, G. K.</creator><creatorcontrib>Garg, R. ; Kneen, L. ; Williams, G. H. ; Adler, G. K.</creatorcontrib><description>Aim
Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity‐induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo‐controlled, double‐blind, randomized, parallel‐group study (NCT01406015).
Methods
Thirty‐two non‐diabetic, obese subjects [body mass index (BMI) 30 to 45 kg/m2] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation (FMD) of brachial artery and renal plasma perfusion by clearance of para‐aminohippurate (PAH).
Results
There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p < 0.02, post‐treatment vs. baseline) and urine aldosterone (11.0 ± 7 vs. 4.8 ± 2.4 µg/g creatinine; p < 0.01) and decreases in systolic blood pressure (116 ± 11 vs. 123 ± 10 mmHg; p < 0.001). There were no changes in these variables in the placebo group. Neither spironolactone nor placebo treatment had a significant effect on ISI or other indices of glucose metabolism [insulin resistance by homeostatic model assessment (HOMA), area under the curve for insulin, area under the curve for glucose], brachial artery reactivity or the renal plasma perfusion values. Changes in these variables were similar in two groups.
Conclusions
We conclude that 6 weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.12224</identifier><identifier>PMID: 24125483</identifier><identifier>CODEN: DOMEF6</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aldosterone ; Aldosterone - metabolism ; Blood pressure ; Blood Pressure - drug effects ; Body Mass Index ; Body Weight ; Brachial Artery ; Cardiovascular diseases ; Comorbidity ; Creatinine ; Diabetes mellitus ; Double-Blind Method ; endothelial function ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiopathology ; Female ; Glucose metabolism ; Humans ; Insulin Resistance ; Male ; Middle Aged ; mineralocorticoid receptor ; Mineralocorticoid Receptor Antagonists - therapeutic use ; Mineralocorticoid receptors ; Obesity ; Obesity - drug therapy ; Obesity - physiopathology ; Perfusion ; Placebos ; Spironolactone - therapeutic use ; Treatment Outcome ; Vasodilation ; Vasodilation - drug effects</subject><ispartof>Diabetes, obesity & metabolism, 2014-03, Vol.16 (3), p.268-272</ispartof><rights>2013 John Wiley & Sons Ltd</rights><rights>2013 John Wiley & Sons Ltd.</rights><rights>2014 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6084-a91704e23c8d65299a0e07753b45e5aa03f6d3185d85e27a760939c58fbba28c3</citedby><cites>FETCH-LOGICAL-c6084-a91704e23c8d65299a0e07753b45e5aa03f6d3185d85e27a760939c58fbba28c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdom.12224$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.12224$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24125483$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garg, R.</creatorcontrib><creatorcontrib>Kneen, L.</creatorcontrib><creatorcontrib>Williams, G. H.</creatorcontrib><creatorcontrib>Adler, G. K.</creatorcontrib><title>Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity‐induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo‐controlled, double‐blind, randomized, parallel‐group study (NCT01406015).
Methods
Thirty‐two non‐diabetic, obese subjects [body mass index (BMI) 30 to 45 kg/m2] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation (FMD) of brachial artery and renal plasma perfusion by clearance of para‐aminohippurate (PAH).
Results
There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p < 0.02, post‐treatment vs. baseline) and urine aldosterone (11.0 ± 7 vs. 4.8 ± 2.4 µg/g creatinine; p < 0.01) and decreases in systolic blood pressure (116 ± 11 vs. 123 ± 10 mmHg; p < 0.001). There were no changes in these variables in the placebo group. Neither spironolactone nor placebo treatment had a significant effect on ISI or other indices of glucose metabolism [insulin resistance by homeostatic model assessment (HOMA), area under the curve for insulin, area under the curve for glucose], brachial artery reactivity or the renal plasma perfusion values. Changes in these variables were similar in two groups.
Conclusions
We conclude that 6 weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aldosterone</subject><subject>Aldosterone - metabolism</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Body Mass Index</subject><subject>Body Weight</subject><subject>Brachial Artery</subject><subject>Cardiovascular diseases</subject><subject>Comorbidity</subject><subject>Creatinine</subject><subject>Diabetes mellitus</subject><subject>Double-Blind Method</subject><subject>endothelial function</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Female</subject><subject>Glucose metabolism</subject><subject>Humans</subject><subject>Insulin Resistance</subject><subject>Male</subject><subject>Middle Aged</subject><subject>mineralocorticoid receptor</subject><subject>Mineralocorticoid Receptor Antagonists - therapeutic use</subject><subject>Mineralocorticoid receptors</subject><subject>Obesity</subject><subject>Obesity - drug therapy</subject><subject>Obesity - physiopathology</subject><subject>Perfusion</subject><subject>Placebos</subject><subject>Spironolactone - therapeutic use</subject><subject>Treatment Outcome</subject><subject>Vasodilation</subject><subject>Vasodilation - drug effects</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtv1DAUhSNERUthwR9AkdjAIq3fjw0SastQUagQICQ2luPctB4Se7ATaP99zUw7AiTwxpbvd4997qmqJxgd4LIOuzgeYEIIu1ftYSZogykR99dn0iiNyG71MOclQohRJR9Uu4Rhwpmie9XqpO_BTXXs69EHSHaILqbJu-i7OoGD1RRTbcNkL2LwuYCh9iHPgw-lnMuNDQ4K0NUQujhdwuDtUPdzcJNfs3VsIUOd53ZZHsqPqp3eDhke3-771efXJ5-O3jRn54vTo1dnjRNIscZqLBEDQp3qBCdaWwRISk5bxoFbi2gvOooV7xQHIq0USFPtuOrb1hLl6H71cqO7mtsROgdhKubMKvnRpmsTrTd_VoK_NBfxh6G6TJCLIvD8ViDF7zPkyYw-OxgGGyDO2WBFZRmzFqigz_5Cl3FOodgzFHHNqKBI_Y_CTDPMFFesUC82lEsx5wT99ssYmV9pm5K2Wadd2Ke_e9ySd_EW4HAD_PQDXP9byRyfv7uTbDYdJVm42nbY9M0ISSU3X94vjHyLFl8_fDw2jN4Anx_EGA</recordid><startdate>201403</startdate><enddate>201403</enddate><creator>Garg, R.</creator><creator>Kneen, L.</creator><creator>Williams, G. H.</creator><creator>Adler, G. K.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7TS</scope><scope>5PM</scope></search><sort><creationdate>201403</creationdate><title>Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects</title><author>Garg, R. ; Kneen, L. ; Williams, G. H. ; Adler, G. K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6084-a91704e23c8d65299a0e07753b45e5aa03f6d3185d85e27a760939c58fbba28c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aldosterone</topic><topic>Aldosterone - metabolism</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Body Mass Index</topic><topic>Body Weight</topic><topic>Brachial Artery</topic><topic>Cardiovascular diseases</topic><topic>Comorbidity</topic><topic>Creatinine</topic><topic>Diabetes mellitus</topic><topic>Double-Blind Method</topic><topic>endothelial function</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Female</topic><topic>Glucose metabolism</topic><topic>Humans</topic><topic>Insulin Resistance</topic><topic>Male</topic><topic>Middle Aged</topic><topic>mineralocorticoid receptor</topic><topic>Mineralocorticoid Receptor Antagonists - therapeutic use</topic><topic>Mineralocorticoid receptors</topic><topic>Obesity</topic><topic>Obesity - drug therapy</topic><topic>Obesity - physiopathology</topic><topic>Perfusion</topic><topic>Placebos</topic><topic>Spironolactone - therapeutic use</topic><topic>Treatment Outcome</topic><topic>Vasodilation</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garg, R.</creatorcontrib><creatorcontrib>Kneen, L.</creatorcontrib><creatorcontrib>Williams, G. H.</creatorcontrib><creatorcontrib>Adler, G. K.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Physical Education Index</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garg, R.</au><au>Kneen, L.</au><au>Williams, G. H.</au><au>Adler, G. K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2014-03</date><risdate>2014</risdate><volume>16</volume><issue>3</issue><spage>268</spage><epage>272</epage><pages>268-272</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><coden>DOMEF6</coden><abstract>Aim
Obese individuals have high aldosterone levels that may contribute to insulin resistance (IR) and endothelial dysfunction leading to obesity‐induced cardiovascular disease. We conducted a study to evaluate the effect of mineralocorticoid receptor antagonism on IR and endothelial function in obese individuals. This was a placebo‐controlled, double‐blind, randomized, parallel‐group study (NCT01406015).
Methods
Thirty‐two non‐diabetic, obese subjects [body mass index (BMI) 30 to 45 kg/m2] with no other medical problems were randomized to 6 weeks of treatment with spironolactone 50 mg daily or placebo. Insulin sensitivity index (ISI) was assessed by Matsuda method, endothelial function by flow mediated vasodilatation (FMD) of brachial artery and renal plasma perfusion by clearance of para‐aminohippurate (PAH).
Results
There was no change in weight, BMI or plasma potassium during the study period. Treatment with spironolactone led to increases in serum aldosterone (7.6 ± 6.6 vs. 3.2 ± 1.3 ng/dl; p < 0.02, post‐treatment vs. baseline) and urine aldosterone (11.0 ± 7 vs. 4.8 ± 2.4 µg/g creatinine; p < 0.01) and decreases in systolic blood pressure (116 ± 11 vs. 123 ± 10 mmHg; p < 0.001). There were no changes in these variables in the placebo group. Neither spironolactone nor placebo treatment had a significant effect on ISI or other indices of glucose metabolism [insulin resistance by homeostatic model assessment (HOMA), area under the curve for insulin, area under the curve for glucose], brachial artery reactivity or the renal plasma perfusion values. Changes in these variables were similar in two groups.
Conclusions
We conclude that 6 weeks of treatment with spironolactone does not change insulin sensitivity or endothelial function in normotensive obese individuals with no other comorbidities.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>24125483</pmid><doi>10.1111/dom.12224</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aldosterone Aldosterone - metabolism Blood pressure Blood Pressure - drug effects Body Mass Index Body Weight Brachial Artery Cardiovascular diseases Comorbidity Creatinine Diabetes mellitus Double-Blind Method endothelial function Endothelium, Vascular - drug effects Endothelium, Vascular - physiopathology Female Glucose metabolism Humans Insulin Resistance Male Middle Aged mineralocorticoid receptor Mineralocorticoid Receptor Antagonists - therapeutic use Mineralocorticoid receptors Obesity Obesity - drug therapy Obesity - physiopathology Perfusion Placebos Spironolactone - therapeutic use Treatment Outcome Vasodilation Vasodilation - drug effects |
| title | Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects |
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