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Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes
Summary Objective To determine the glucose‐lowering mechanism of action and the effects of a quick‐release bromocriptine‐QR, a D2‐dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D). Study design and methods Fifteen poorly controlled T2D treated with metformin plu...
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| Published in: | Endocrinology, diabetes & metabolism diabetes & metabolism, 2018-10, Vol.1 (4), p.e00034-n/a |
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| creator | Alatrach, Mariam Agyin, Christina Adams, John Chilton, Robert Triplitt, Curtis DeFronzo, Ralph A. Cersosimo, Eugenio |
| description | Summary
Objective
To determine the glucose‐lowering mechanism of action and the effects of a quick‐release bromocriptine‐QR, a D2‐dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D).
Study design and methods
Fifteen poorly controlled T2D treated with metformin plus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) were studied after 4 months of Cycloset, 3.2 mg/d. Subjects received a 5‐hour double‐tracer (iv 3‐3H‐glucose and oral 14C‐glucose) mixed meal test (MMT) to quantitate rates of endogenous glucose production (EGP), oral glucose appearance (RaO) and disappearance (Rd) pre‐ and post‐Cycloset. Vascular assessments included 2‐day continuous BP monitoring, reactive hyperaemia index (RHI) and arterial stiffness (AS).
Results
HbA1c decreased from 8.3 ± 0.3% to 7.7 ± 0.2% (P |
| doi_str_mv | 10.1002/edm2.34 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6354804</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2187033087</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3634-a7c9dd2f93358825deb5c99374e0ee5b6aaaeb62a9b51830f6ee3a3940c56403</originalsourceid><addsrcrecordid>eNp1kdFqFDEYhYMottTiG0jAC4WyNZNMssmNUGpdhRW96H3IJP9sU7KTMcnssnd9BJ_RJ2mWraUKXuVAvv_8JzkIvW7IeUMI_QBuTc9Z-wwdU6bkTFEmnz_RR-g051tCSKOUEoS-REeMyIZzQY_R3SJMNmbAIW4h-WGFzeDwxmQ7BZPwmGIBW_wGMPR9VRnHHtudDXWmYOMcOFwiXix__L771eAEFsYSEzarOPhccT_g0RQPQ9VbX25w2Y2AKXbedFAgv0IvehMynD6cJ-j689X15ZfZ8vvi6-XFcmaZYO3MzK1yjvaKMS4l5Q46bpVi8xYIAO-EMQY6QY3qeCMZ6QUAM0y1xHLREnaCPh5sx6lbg7M1TzJBj8mvTdrpaLz--2bwN3oVN1ow3krSVoP3DwYp_pwgF7322UIIZoA4ZU0bOSesfuy8om__QW_jlIb6Ok2pEFJxRnil3h0om2LOCfrHMA3R-171vlfN9qvfPM3-yP1psQJnB2DrA-z-56OvPn2j1e4elzeuOg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2266895305</pqid></control><display><type>article</type><title>Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes</title><source>PMC (PubMed Central)</source><source>Wiley_OA刊</source><source>Publicly Available Content (ProQuest)</source><creator>Alatrach, Mariam ; Agyin, Christina ; Adams, John ; Chilton, Robert ; Triplitt, Curtis ; DeFronzo, Ralph A. ; Cersosimo, Eugenio</creator><creatorcontrib>Alatrach, Mariam ; Agyin, Christina ; Adams, John ; Chilton, Robert ; Triplitt, Curtis ; DeFronzo, Ralph A. ; Cersosimo, Eugenio</creatorcontrib><description>Summary
Objective
To determine the glucose‐lowering mechanism of action and the effects of a quick‐release bromocriptine‐QR, a D2‐dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D).
Study design and methods
Fifteen poorly controlled T2D treated with metformin plus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) were studied after 4 months of Cycloset, 3.2 mg/d. Subjects received a 5‐hour double‐tracer (iv 3‐3H‐glucose and oral 14C‐glucose) mixed meal test (MMT) to quantitate rates of endogenous glucose production (EGP), oral glucose appearance (RaO) and disappearance (Rd) pre‐ and post‐Cycloset. Vascular assessments included 2‐day continuous BP monitoring, reactive hyperaemia index (RHI) and arterial stiffness (AS).
Results
HbA1c decreased from 8.3 ± 0.3% to 7.7 ± 0.2% (P < 0.05), fasting plasma glucose did not change (143 ± 4 vs 147 ± 5) and mean plasma glucose during MTT decreased from 223 ± 3 to 210 ± 4 mg/dL (P < 0.05) after Cycloset. Basal EGP (2.2 ± 0.2 vs 2.1 ± 0.2 mg/kg min) was unchanged, but there was greater MMT suppression (1.1 ± 0.1 vs 0.7 ± 0.1, P < 0.05). After Cycloset, RaO declined from 2.0 ± 0.1 to 1.7 ± 0.2 mg/kg min and peripheral oral glucose appearance from 53.1 ± 3.2 to 44.4 ± 3.1 g (P < 0.01). There were no changes in plasma insulin or glucagon concentration. Systolic (134 ± 4 vs 126 ± 6), diastolic (78 ± 3 vs 73 ± 4), mean BP (97 ± 5 vs 90 ± 4) and pulse pressure (54 ± 2 vs 51 ± 2 mm Hg) were reduced; RHI increased from 1.4 ± 0.1 to 1.9 ± 0.3 au and AS decreased modestly (19.8 ± 4.1 to 16.2 ± 3.7 au, P = NS).
Conclusions
Addition of Cycloset to GLP‐1 RA improved vascular indices and postprandial hyperglycaemia in T2DM primarily by lowering oral glucose appearance, suggesting that hepatic glucose uptake was enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with T2DM.
This article provides evidence that the addition of a D2‐dopamine agonist (Cycloset) to a GLP‐1 RA improves vascular indices and attenuates postprandial hyperglycaemia in patients with type 2 diabetes. Cycloset decreases oral glucose appearance, suggesting that hepatic glucose uptake is enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with type 2 diabetes.</description><identifier>ISSN: 2398-9238</identifier><identifier>EISSN: 2398-9238</identifier><identifier>DOI: 10.1002/edm2.34</identifier><identifier>PMID: 30815562</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>bromocriptine ; Cardiovascular disease ; Diabetes ; Dopamine ; GLP-1 receptor agonists ; Glucose ; glucose efficacy ; Hyperglycemia ; Hypertension ; Insulin resistance ; Metabolism ; Original ; vascular protection</subject><ispartof>Endocrinology, diabetes & metabolism, 2018-10, Vol.1 (4), p.e00034-n/a</ispartof><rights>2018 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3634-a7c9dd2f93358825deb5c99374e0ee5b6aaaeb62a9b51830f6ee3a3940c56403</citedby><cites>FETCH-LOGICAL-c3634-a7c9dd2f93358825deb5c99374e0ee5b6aaaeb62a9b51830f6ee3a3940c56403</cites><orcidid>0000-0002-2573-0208 ; 0000-0003-0195-5063 ; 0000-0003-3839-1724</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2266895305/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2266895305?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11562,25753,27924,27925,37012,37013,44590,46052,46476,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30815562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alatrach, Mariam</creatorcontrib><creatorcontrib>Agyin, Christina</creatorcontrib><creatorcontrib>Adams, John</creatorcontrib><creatorcontrib>Chilton, Robert</creatorcontrib><creatorcontrib>Triplitt, Curtis</creatorcontrib><creatorcontrib>DeFronzo, Ralph A.</creatorcontrib><creatorcontrib>Cersosimo, Eugenio</creatorcontrib><title>Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes</title><title>Endocrinology, diabetes & metabolism</title><addtitle>Endocrinol Diabetes Metab</addtitle><description>Summary
Objective
To determine the glucose‐lowering mechanism of action and the effects of a quick‐release bromocriptine‐QR, a D2‐dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D).
Study design and methods
Fifteen poorly controlled T2D treated with metformin plus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) were studied after 4 months of Cycloset, 3.2 mg/d. Subjects received a 5‐hour double‐tracer (iv 3‐3H‐glucose and oral 14C‐glucose) mixed meal test (MMT) to quantitate rates of endogenous glucose production (EGP), oral glucose appearance (RaO) and disappearance (Rd) pre‐ and post‐Cycloset. Vascular assessments included 2‐day continuous BP monitoring, reactive hyperaemia index (RHI) and arterial stiffness (AS).
Results
HbA1c decreased from 8.3 ± 0.3% to 7.7 ± 0.2% (P < 0.05), fasting plasma glucose did not change (143 ± 4 vs 147 ± 5) and mean plasma glucose during MTT decreased from 223 ± 3 to 210 ± 4 mg/dL (P < 0.05) after Cycloset. Basal EGP (2.2 ± 0.2 vs 2.1 ± 0.2 mg/kg min) was unchanged, but there was greater MMT suppression (1.1 ± 0.1 vs 0.7 ± 0.1, P < 0.05). After Cycloset, RaO declined from 2.0 ± 0.1 to 1.7 ± 0.2 mg/kg min and peripheral oral glucose appearance from 53.1 ± 3.2 to 44.4 ± 3.1 g (P < 0.01). There were no changes in plasma insulin or glucagon concentration. Systolic (134 ± 4 vs 126 ± 6), diastolic (78 ± 3 vs 73 ± 4), mean BP (97 ± 5 vs 90 ± 4) and pulse pressure (54 ± 2 vs 51 ± 2 mm Hg) were reduced; RHI increased from 1.4 ± 0.1 to 1.9 ± 0.3 au and AS decreased modestly (19.8 ± 4.1 to 16.2 ± 3.7 au, P = NS).
Conclusions
Addition of Cycloset to GLP‐1 RA improved vascular indices and postprandial hyperglycaemia in T2DM primarily by lowering oral glucose appearance, suggesting that hepatic glucose uptake was enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with T2DM.
This article provides evidence that the addition of a D2‐dopamine agonist (Cycloset) to a GLP‐1 RA improves vascular indices and attenuates postprandial hyperglycaemia in patients with type 2 diabetes. Cycloset decreases oral glucose appearance, suggesting that hepatic glucose uptake is enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with type 2 diabetes.</description><subject>bromocriptine</subject><subject>Cardiovascular disease</subject><subject>Diabetes</subject><subject>Dopamine</subject><subject>GLP-1 receptor agonists</subject><subject>Glucose</subject><subject>glucose efficacy</subject><subject>Hyperglycemia</subject><subject>Hypertension</subject><subject>Insulin resistance</subject><subject>Metabolism</subject><subject>Original</subject><subject>vascular protection</subject><issn>2398-9238</issn><issn>2398-9238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><recordid>eNp1kdFqFDEYhYMottTiG0jAC4WyNZNMssmNUGpdhRW96H3IJP9sU7KTMcnssnd9BJ_RJ2mWraUKXuVAvv_8JzkIvW7IeUMI_QBuTc9Z-wwdU6bkTFEmnz_RR-g051tCSKOUEoS-REeMyIZzQY_R3SJMNmbAIW4h-WGFzeDwxmQ7BZPwmGIBW_wGMPR9VRnHHtudDXWmYOMcOFwiXix__L771eAEFsYSEzarOPhccT_g0RQPQ9VbX25w2Y2AKXbedFAgv0IvehMynD6cJ-j689X15ZfZ8vvi6-XFcmaZYO3MzK1yjvaKMS4l5Q46bpVi8xYIAO-EMQY6QY3qeCMZ6QUAM0y1xHLREnaCPh5sx6lbg7M1TzJBj8mvTdrpaLz--2bwN3oVN1ow3krSVoP3DwYp_pwgF7322UIIZoA4ZU0bOSesfuy8om__QW_jlIb6Ok2pEFJxRnil3h0om2LOCfrHMA3R-171vlfN9qvfPM3-yP1psQJnB2DrA-z-56OvPn2j1e4elzeuOg</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Alatrach, Mariam</creator><creator>Agyin, Christina</creator><creator>Adams, John</creator><creator>Chilton, Robert</creator><creator>Triplitt, Curtis</creator><creator>DeFronzo, Ralph A.</creator><creator>Cersosimo, Eugenio</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2573-0208</orcidid><orcidid>https://orcid.org/0000-0003-0195-5063</orcidid><orcidid>https://orcid.org/0000-0003-3839-1724</orcidid></search><sort><creationdate>201810</creationdate><title>Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes</title><author>Alatrach, Mariam ; Agyin, Christina ; Adams, John ; Chilton, Robert ; Triplitt, Curtis ; DeFronzo, Ralph A. ; Cersosimo, Eugenio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3634-a7c9dd2f93358825deb5c99374e0ee5b6aaaeb62a9b51830f6ee3a3940c56403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>bromocriptine</topic><topic>Cardiovascular disease</topic><topic>Diabetes</topic><topic>Dopamine</topic><topic>GLP-1 receptor agonists</topic><topic>Glucose</topic><topic>glucose efficacy</topic><topic>Hyperglycemia</topic><topic>Hypertension</topic><topic>Insulin resistance</topic><topic>Metabolism</topic><topic>Original</topic><topic>vascular protection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alatrach, Mariam</creatorcontrib><creatorcontrib>Agyin, Christina</creatorcontrib><creatorcontrib>Adams, John</creatorcontrib><creatorcontrib>Chilton, Robert</creatorcontrib><creatorcontrib>Triplitt, Curtis</creatorcontrib><creatorcontrib>DeFronzo, Ralph A.</creatorcontrib><creatorcontrib>Cersosimo, Eugenio</creatorcontrib><collection>Wiley_OA刊</collection><collection>Wiley-Blackwell Free Backfiles(OpenAccess)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology, diabetes & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alatrach, Mariam</au><au>Agyin, Christina</au><au>Adams, John</au><au>Chilton, Robert</au><au>Triplitt, Curtis</au><au>DeFronzo, Ralph A.</au><au>Cersosimo, Eugenio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes</atitle><jtitle>Endocrinology, diabetes & metabolism</jtitle><addtitle>Endocrinol Diabetes Metab</addtitle><date>2018-10</date><risdate>2018</risdate><volume>1</volume><issue>4</issue><spage>e00034</spage><epage>n/a</epage><pages>e00034-n/a</pages><issn>2398-9238</issn><eissn>2398-9238</eissn><abstract>Summary
Objective
To determine the glucose‐lowering mechanism of action and the effects of a quick‐release bromocriptine‐QR, a D2‐dopamine agonist (Cycloset) on vascular function in patients with type 2 diabetes (T2D).
Study design and methods
Fifteen poorly controlled T2D treated with metformin plus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) were studied after 4 months of Cycloset, 3.2 mg/d. Subjects received a 5‐hour double‐tracer (iv 3‐3H‐glucose and oral 14C‐glucose) mixed meal test (MMT) to quantitate rates of endogenous glucose production (EGP), oral glucose appearance (RaO) and disappearance (Rd) pre‐ and post‐Cycloset. Vascular assessments included 2‐day continuous BP monitoring, reactive hyperaemia index (RHI) and arterial stiffness (AS).
Results
HbA1c decreased from 8.3 ± 0.3% to 7.7 ± 0.2% (P < 0.05), fasting plasma glucose did not change (143 ± 4 vs 147 ± 5) and mean plasma glucose during MTT decreased from 223 ± 3 to 210 ± 4 mg/dL (P < 0.05) after Cycloset. Basal EGP (2.2 ± 0.2 vs 2.1 ± 0.2 mg/kg min) was unchanged, but there was greater MMT suppression (1.1 ± 0.1 vs 0.7 ± 0.1, P < 0.05). After Cycloset, RaO declined from 2.0 ± 0.1 to 1.7 ± 0.2 mg/kg min and peripheral oral glucose appearance from 53.1 ± 3.2 to 44.4 ± 3.1 g (P < 0.01). There were no changes in plasma insulin or glucagon concentration. Systolic (134 ± 4 vs 126 ± 6), diastolic (78 ± 3 vs 73 ± 4), mean BP (97 ± 5 vs 90 ± 4) and pulse pressure (54 ± 2 vs 51 ± 2 mm Hg) were reduced; RHI increased from 1.4 ± 0.1 to 1.9 ± 0.3 au and AS decreased modestly (19.8 ± 4.1 to 16.2 ± 3.7 au, P = NS).
Conclusions
Addition of Cycloset to GLP‐1 RA improved vascular indices and postprandial hyperglycaemia in T2DM primarily by lowering oral glucose appearance, suggesting that hepatic glucose uptake was enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with T2DM.
This article provides evidence that the addition of a D2‐dopamine agonist (Cycloset) to a GLP‐1 RA improves vascular indices and attenuates postprandial hyperglycaemia in patients with type 2 diabetes. Cycloset decreases oral glucose appearance, suggesting that hepatic glucose uptake is enhanced. Improved vascular indices may explain the reduction in cardiovascular events observed with Cycloset therapy in patients with type 2 diabetes.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>30815562</pmid><doi>10.1002/edm2.34</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2573-0208</orcidid><orcidid>https://orcid.org/0000-0003-0195-5063</orcidid><orcidid>https://orcid.org/0000-0003-3839-1724</orcidid><oa>free_for_read</oa></addata></record> |
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| source | PMC (PubMed Central); Wiley_OA刊; Publicly Available Content (ProQuest) |
| subjects | bromocriptine Cardiovascular disease Diabetes Dopamine GLP-1 receptor agonists Glucose glucose efficacy Hyperglycemia Hypertension Insulin resistance Metabolism Original vascular protection |
| title | Glucose lowering and vascular protective effects of cycloset added to GLP‐1 receptor agonists in patients with type 2 diabetes |
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