Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia
OBJECTIVE:--Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIG...
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| Veröffentlicht in: | Diabetes care 2005-06, Vol.28 (6), p.1419-1424 |
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| creator | Koh, Kwang Kon Han, Seung Hwan Quon, Michael J Yeal Ahn, Jeong Shin, Eak Kyun |
| description | OBJECTIVE:--Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS--We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS:--Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 ± 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 ± 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 ± 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 ± 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS:--Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients. |
| doi_str_mv | 10.2337/diacare.28.6.1419 |
| format | Article |
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We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS--We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS:--Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 ± 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 ± 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 ± 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 ± 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS:--Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.</description><identifier>ISSN: 0149-5992</identifier><identifier>EISSN: 1935-5548</identifier><identifier>DOI: 10.2337/diacare.28.6.1419</identifier><identifier>PMID: 15920062</identifier><identifier>CODEN: DICAD2</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adiponectin ; Biological and medical sciences ; Blood ; Blood Flow Velocity - drug effects ; Body Mass Index ; Brachial Artery - drug effects ; Brachial Artery - physiopathology ; Cardiovascular disease ; Care and treatment ; Case studies ; Coronary heart disease ; Cross-Over Studies ; Diabetes. Impaired glucose tolerance ; Disorders of blood lipids. Hyperlipoproteinemia ; Double-Blind Method ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiopathology ; Female ; Fenofibrate - therapeutic use ; Homeopathy ; Humans ; Hyperemia - drug therapy ; Hyperemia - physiopathology ; Hyperlipidemia ; Hypertriglyceridemia - blood ; Hypertriglyceridemia - drug therapy ; Hypertriglyceridemia - physiopathology ; Hypolipidemic Agents - therapeutic use ; Insulin ; Insulin Resistance ; Intercellular Signaling Peptides and Proteins - blood ; Male ; Materia medica and therapeutics ; Medical sciences ; Metabolic diseases ; Metabolic Syndrome - blood ; Metabolic Syndrome - drug therapy ; Metabolic Syndrome - physiopathology ; Metabolism ; Middle Aged ; Patient Selection ; Placebos ; Risk factors ; Therapeutics ; Therapy</subject><ispartof>Diabetes care, 2005-06, Vol.28 (6), p.1419-1424</ispartof><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 American Diabetes Association</rights><rights>Copyright American Diabetes Association Jun 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-b1915f9436fdb294f3a01617650a06668aba41d51d002b5ae90592fe54d8cebc3</citedby><cites>FETCH-LOGICAL-c504t-b1915f9436fdb294f3a01617650a06668aba41d51d002b5ae90592fe54d8cebc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16830367$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15920062$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koh, Kwang Kon</creatorcontrib><creatorcontrib>Han, Seung Hwan</creatorcontrib><creatorcontrib>Quon, Michael J</creatorcontrib><creatorcontrib>Yeal Ahn, Jeong</creatorcontrib><creatorcontrib>Shin, Eak Kyun</creatorcontrib><title>Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia</title><title>Diabetes care</title><addtitle>Diabetes Care</addtitle><description>OBJECTIVE:--Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS--We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS:--Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 ± 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 ± 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 ± 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 ± 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS:--Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.</description><subject>Adiponectin</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Blood Flow Velocity - drug effects</subject><subject>Body Mass Index</subject><subject>Brachial Artery - drug effects</subject><subject>Brachial Artery - physiopathology</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Case studies</subject><subject>Coronary heart disease</subject><subject>Cross-Over Studies</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Disorders of blood lipids. Hyperlipoproteinemia</subject><subject>Double-Blind Method</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Female</subject><subject>Fenofibrate - therapeutic use</subject><subject>Homeopathy</subject><subject>Humans</subject><subject>Hyperemia - drug therapy</subject><subject>Hyperemia - physiopathology</subject><subject>Hyperlipidemia</subject><subject>Hypertriglyceridemia - blood</subject><subject>Hypertriglyceridemia - drug therapy</subject><subject>Hypertriglyceridemia - physiopathology</subject><subject>Hypolipidemic Agents - therapeutic use</subject><subject>Insulin</subject><subject>Insulin Resistance</subject><subject>Intercellular Signaling Peptides and Proteins - blood</subject><subject>Male</subject><subject>Materia medica and therapeutics</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Metabolic Syndrome - blood</subject><subject>Metabolic Syndrome - drug therapy</subject><subject>Metabolic Syndrome - physiopathology</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Patient Selection</subject><subject>Placebos</subject><subject>Risk factors</subject><subject>Therapeutics</subject><subject>Therapy</subject><issn>0149-5992</issn><issn>1935-5548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkd-KEzEUxgdR3Lr6AN5oELwRpubfTCeXde26CwUXdfFyOJM5abNMk5qkK30KX9kMU9ibEkhC-J3vyzlfUbxldM6FWHzuLWgIOOfNvJ4zydSzYsaUqMqqks3zYkaZVGWlFL8oXsX4QCmVsmleFhesUpzSms-Kf1_QobHawkBWxqBOkXhDrtF5Y7sACUny5Ha3D_4Rycr1Pm1xGOmvx2gOTifrHQHXkx9gI5Jlb_feZRnryBofcYgk3-4gWXRZ-rdNW3IX7A7Ckdwc9xhSsJvhqDHYHncWXhcvDAwR35zOy-L-evXr6qZcf_92e7Vcl7qiMpUdU6wySora9B1X0gigrGaLuqJA67puoAPJ-or1lPKuAlQ0t2ywkn2jsdPisvgw6ebG_hwwpvbBH4LLli3ngkpFFypD5QRtYMDWOuNTAL3JEwsw-HFu-XnJhBD1QvIm8_MzfF5ja_psAZsKdPAxBjTtfppNy2g7RtyeIm5509btGHGueXf6-aHbYf9Ucco0Ax9PAEQNgwngtI1PXN0Imv0z92nitnaz_WuzSTbrMGE86_p-gg34FjYhC97_5JQJyui4U_Ef-4zJgw</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Koh, Kwang Kon</creator><creator>Han, Seung Hwan</creator><creator>Quon, Michael J</creator><creator>Yeal Ahn, Jeong</creator><creator>Shin, Eak Kyun</creator><general>American Diabetes Association</general><scope>FBQ</scope><scope>IQODW</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>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0K</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope></search><sort><creationdate>20050601</creationdate><title>Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia</title><author>Koh, Kwang Kon ; Han, Seung Hwan ; Quon, Michael J ; Yeal Ahn, Jeong ; Shin, Eak Kyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-b1915f9436fdb294f3a01617650a06668aba41d51d002b5ae90592fe54d8cebc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adiponectin</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Blood Flow Velocity - drug effects</topic><topic>Body Mass Index</topic><topic>Brachial Artery - drug effects</topic><topic>Brachial Artery - physiopathology</topic><topic>Cardiovascular disease</topic><topic>Care and treatment</topic><topic>Case studies</topic><topic>Coronary heart disease</topic><topic>Cross-Over Studies</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Disorders of blood lipids. Hyperlipoproteinemia</topic><topic>Double-Blind Method</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Female</topic><topic>Fenofibrate - therapeutic use</topic><topic>Homeopathy</topic><topic>Humans</topic><topic>Hyperemia - drug therapy</topic><topic>Hyperemia - physiopathology</topic><topic>Hyperlipidemia</topic><topic>Hypertriglyceridemia - blood</topic><topic>Hypertriglyceridemia - drug therapy</topic><topic>Hypertriglyceridemia - physiopathology</topic><topic>Hypolipidemic Agents - therapeutic use</topic><topic>Insulin</topic><topic>Insulin Resistance</topic><topic>Intercellular Signaling Peptides and Proteins - blood</topic><topic>Male</topic><topic>Materia medica and therapeutics</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Metabolic Syndrome - blood</topic><topic>Metabolic Syndrome - drug therapy</topic><topic>Metabolic Syndrome - physiopathology</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Patient Selection</topic><topic>Placebos</topic><topic>Risk factors</topic><topic>Therapeutics</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koh, Kwang Kon</creatorcontrib><creatorcontrib>Han, Seung Hwan</creatorcontrib><creatorcontrib>Quon, Michael J</creatorcontrib><creatorcontrib>Yeal Ahn, Jeong</creatorcontrib><creatorcontrib>Shin, Eak Kyun</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</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 & Allied Health Database</collection><collection>Agricultural Science Collection</collection><collection>Health & 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Hypertriglyceridemia</atitle><jtitle>Diabetes care</jtitle><addtitle>Diabetes Care</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>28</volume><issue>6</issue><spage>1419</spage><epage>1424</epage><pages>1419-1424</pages><issn>0149-5992</issn><eissn>1935-5548</eissn><coden>DICAD2</coden><abstract>OBJECTIVE:--Improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS--We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS:--Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 ± 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 ± 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 ± 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 ± 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS:--Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>15920062</pmid><doi>10.2337/diacare.28.6.1419</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetes care, 2005-06, Vol.28 (6), p.1419-1424 |
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| subjects | Adiponectin Biological and medical sciences Blood Blood Flow Velocity - drug effects Body Mass Index Brachial Artery - drug effects Brachial Artery - physiopathology Cardiovascular disease Care and treatment Case studies Coronary heart disease Cross-Over Studies Diabetes. Impaired glucose tolerance Disorders of blood lipids. Hyperlipoproteinemia Double-Blind Method Endocrine pancreas. Apud cells (diseases) Endocrinopathies Endothelium, Vascular - drug effects Endothelium, Vascular - physiopathology Female Fenofibrate - therapeutic use Homeopathy Humans Hyperemia - drug therapy Hyperemia - physiopathology Hyperlipidemia Hypertriglyceridemia - blood Hypertriglyceridemia - drug therapy Hypertriglyceridemia - physiopathology Hypolipidemic Agents - therapeutic use Insulin Insulin Resistance Intercellular Signaling Peptides and Proteins - blood Male Materia medica and therapeutics Medical sciences Metabolic diseases Metabolic Syndrome - blood Metabolic Syndrome - drug therapy Metabolic Syndrome - physiopathology Metabolism Middle Aged Patient Selection Placebos Risk factors Therapeutics Therapy |
| title | Beneficial Effects of Fenofibrate to Improve Endothelial Dysfunction and Raise Adiponectin Levels in Patients With Primary Hypertriglyceridemia |
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