Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome
Aim This study investigated the effect of long‐term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. Methods In this double‐blind randomized placebo‐controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2014-06, Vol.16 (6), p.545-552 |
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| creator | Aye, M. M. Kilpatrick, E. S. Afolabi, P. Wootton, S. A. Rigby, A. S. Coady, A. M. Sandeman, D. D. Atkin, S. L. |
| description | Aim
This study investigated the effect of long‐term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS.
Methods
In this double‐blind randomized placebo‐controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention.
Results
By 12 weeks, niacin/laropiprant lowered low‐density lipoprotein cholesterol (LDL‐c) (13%) and increased HDL‐c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA‐IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP.
Conclusions
In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β‐cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS. |
| doi_str_mv | 10.1111/dom.12255 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1519259986</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3059407050</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4195-e93053be8d82e452ca5e0fa757319f21cb2d071f16dc262e2f25fdb7ee9a52843</originalsourceid><addsrcrecordid>eNp9kcFuFSEUhidGY2t14QsYEje6mF5gYGZYmqu2mta60OiOcOFQaRmYwox1XsZnld7bdmGihIQT8p2PE_6qek7wISlrZeJwSCjl_EG1T1jb1KSh7cNtTeteYLpXPcn5AmPMmr57XO1RxjDBvdivfn-OeRqTCsYpj8Ba0FNG0SIfw3k9QRpQcEq7sPIqxdHdoBOaM6AY0LmfdSxl6Ubejc6gASa1id7lYXtZGK2ScfGnynouBpRcvkQuoFFNDkJ56tpNP9AY_aKXPDmNCpoWlJdgUhzgafXIKp_h2e15UH19_-7L-rg-OTv6sH5zUmtGBK9BNJg3G-hNT4FxqhUHbFXHu4YIS4neUIM7YklrNG0pUEu5NZsOQChOe9YcVK923jHFqxnyJAeXNXivAsQ5S8KJoFyIvi3oy7_QizinUKaTZQjBcIc5_h9VXH3HyhaFer2jdIo5J7ByTG4oHyAJljfRyhKt3EZb2Be3xnkzgLkn77IswGoHXDsPy79N8u3Z6Z2y3nW4PMGv-w6VLmXbNR2X3z4dyTVrv7en_Fh-bP4AXHa-zw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1518748749</pqid></control><display><type>article</type><title>Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Aye, M. M. ; Kilpatrick, E. S. ; Afolabi, P. ; Wootton, S. A. ; Rigby, A. S. ; Coady, A. M. ; Sandeman, D. D. ; Atkin, S. L.</creator><creatorcontrib>Aye, M. M. ; Kilpatrick, E. S. ; Afolabi, P. ; Wootton, S. A. ; Rigby, A. S. ; Coady, A. M. ; Sandeman, D. D. ; Atkin, S. L.</creatorcontrib><description>Aim
This study investigated the effect of long‐term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS.
Methods
In this double‐blind randomized placebo‐controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention.
Results
By 12 weeks, niacin/laropiprant lowered low‐density lipoprotein cholesterol (LDL‐c) (13%) and increased HDL‐c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA‐IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP.
Conclusions
In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β‐cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.12255</identifier><identifier>PMID: 24401089</identifier><identifier>CODEN: DOMEF6</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Beta cells ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Cardiovascular diseases ; Cardiovascular Diseases - metabolism ; Cholesterol ; Cholesterol, HDL - blood ; Cholesterol, LDL - blood ; Double-Blind Method ; Drug Therapy, Combination ; endothelial dysfunction ; Fasting ; Female ; Glucose ; Glucose metabolism ; High density lipoprotein ; Humans ; Hypertriglyceridemia - drug therapy ; Hypertriglyceridemia - metabolism ; Hypolipidemic Agents - administration & dosage ; Indoles - administration & dosage ; Insulin resistance ; Lipid metabolism ; Lipid Metabolism - drug effects ; Low density lipoprotein ; Niacin - administration & dosage ; niacin/laropiprant ; Nicotinic acid ; Placebos ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - drug therapy ; Polycystic Ovary Syndrome - metabolism ; Postprandial Period - drug effects ; Postprandial Period - physiology ; Risk Reduction Behavior ; Treatment Outcome ; Triglycerides ; Triglycerides - blood ; Vitamin B ; Young Adult</subject><ispartof>Diabetes, obesity & metabolism, 2014-06, Vol.16 (6), p.545-552</ispartof><rights>2014 John Wiley & Sons Ltd</rights><rights>2014 John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4195-e93053be8d82e452ca5e0fa757319f21cb2d071f16dc262e2f25fdb7ee9a52843</citedby><cites>FETCH-LOGICAL-c4195-e93053be8d82e452ca5e0fa757319f21cb2d071f16dc262e2f25fdb7ee9a52843</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.12255$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdom.12255$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24401089$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aye, M. M.</creatorcontrib><creatorcontrib>Kilpatrick, E. S.</creatorcontrib><creatorcontrib>Afolabi, P.</creatorcontrib><creatorcontrib>Wootton, S. A.</creatorcontrib><creatorcontrib>Rigby, A. S.</creatorcontrib><creatorcontrib>Coady, A. M.</creatorcontrib><creatorcontrib>Sandeman, D. D.</creatorcontrib><creatorcontrib>Atkin, S. L.</creatorcontrib><title>Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aim
This study investigated the effect of long‐term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS.
Methods
In this double‐blind randomized placebo‐controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention.
Results
By 12 weeks, niacin/laropiprant lowered low‐density lipoprotein cholesterol (LDL‐c) (13%) and increased HDL‐c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA‐IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP.
Conclusions
In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β‐cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.</description><subject>Adult</subject><subject>Beta cells</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - metabolism</subject><subject>Cholesterol</subject><subject>Cholesterol, HDL - blood</subject><subject>Cholesterol, LDL - blood</subject><subject>Double-Blind Method</subject><subject>Drug Therapy, Combination</subject><subject>endothelial dysfunction</subject><subject>Fasting</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose metabolism</subject><subject>High density lipoprotein</subject><subject>Humans</subject><subject>Hypertriglyceridemia - drug therapy</subject><subject>Hypertriglyceridemia - metabolism</subject><subject>Hypolipidemic Agents - administration & dosage</subject><subject>Indoles - administration & dosage</subject><subject>Insulin resistance</subject><subject>Lipid metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Low density lipoprotein</subject><subject>Niacin - administration & dosage</subject><subject>niacin/laropiprant</subject><subject>Nicotinic acid</subject><subject>Placebos</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - drug therapy</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Postprandial Period - drug effects</subject><subject>Postprandial Period - physiology</subject><subject>Risk Reduction Behavior</subject><subject>Treatment Outcome</subject><subject>Triglycerides</subject><subject>Triglycerides - blood</subject><subject>Vitamin B</subject><subject>Young Adult</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>eNp9kcFuFSEUhidGY2t14QsYEje6mF5gYGZYmqu2mta60OiOcOFQaRmYwox1XsZnld7bdmGihIQT8p2PE_6qek7wISlrZeJwSCjl_EG1T1jb1KSh7cNtTeteYLpXPcn5AmPMmr57XO1RxjDBvdivfn-OeRqTCsYpj8Ba0FNG0SIfw3k9QRpQcEq7sPIqxdHdoBOaM6AY0LmfdSxl6Ubejc6gASa1id7lYXtZGK2ScfGnynouBpRcvkQuoFFNDkJ56tpNP9AY_aKXPDmNCpoWlJdgUhzgafXIKp_h2e15UH19_-7L-rg-OTv6sH5zUmtGBK9BNJg3G-hNT4FxqhUHbFXHu4YIS4neUIM7YklrNG0pUEu5NZsOQChOe9YcVK923jHFqxnyJAeXNXivAsQ5S8KJoFyIvi3oy7_QizinUKaTZQjBcIc5_h9VXH3HyhaFer2jdIo5J7ByTG4oHyAJljfRyhKt3EZb2Be3xnkzgLkn77IswGoHXDsPy79N8u3Z6Z2y3nW4PMGv-w6VLmXbNR2X3z4dyTVrv7en_Fh-bP4AXHa-zw</recordid><startdate>201406</startdate><enddate>201406</enddate><creator>Aye, M. M.</creator><creator>Kilpatrick, E. S.</creator><creator>Afolabi, P.</creator><creator>Wootton, S. A.</creator><creator>Rigby, A. S.</creator><creator>Coady, A. M.</creator><creator>Sandeman, D. D.</creator><creator>Atkin, S. L.</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>7X8</scope></search><sort><creationdate>201406</creationdate><title>Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome</title><author>Aye, M. M. ; Kilpatrick, E. S. ; Afolabi, P. ; Wootton, S. A. ; Rigby, A. S. ; Coady, A. M. ; Sandeman, D. D. ; Atkin, S. L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4195-e93053be8d82e452ca5e0fa757319f21cb2d071f16dc262e2f25fdb7ee9a52843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Beta cells</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - metabolism</topic><topic>Cholesterol</topic><topic>Cholesterol, HDL - blood</topic><topic>Cholesterol, LDL - blood</topic><topic>Double-Blind Method</topic><topic>Drug Therapy, Combination</topic><topic>endothelial dysfunction</topic><topic>Fasting</topic><topic>Female</topic><topic>Glucose</topic><topic>Glucose metabolism</topic><topic>High density lipoprotein</topic><topic>Humans</topic><topic>Hypertriglyceridemia - drug therapy</topic><topic>Hypertriglyceridemia - metabolism</topic><topic>Hypolipidemic Agents - administration & dosage</topic><topic>Indoles - administration & dosage</topic><topic>Insulin resistance</topic><topic>Lipid metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Low density lipoprotein</topic><topic>Niacin - administration & dosage</topic><topic>niacin/laropiprant</topic><topic>Nicotinic acid</topic><topic>Placebos</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - drug therapy</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Postprandial Period - drug effects</topic><topic>Postprandial Period - physiology</topic><topic>Risk Reduction Behavior</topic><topic>Treatment Outcome</topic><topic>Triglycerides</topic><topic>Triglycerides - blood</topic><topic>Vitamin B</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aye, M. M.</creatorcontrib><creatorcontrib>Kilpatrick, E. S.</creatorcontrib><creatorcontrib>Afolabi, P.</creatorcontrib><creatorcontrib>Wootton, S. A.</creatorcontrib><creatorcontrib>Rigby, A. S.</creatorcontrib><creatorcontrib>Coady, A. M.</creatorcontrib><creatorcontrib>Sandeman, D. D.</creatorcontrib><creatorcontrib>Atkin, S. L.</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>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aye, M. M.</au><au>Kilpatrick, E. S.</au><au>Afolabi, P.</au><au>Wootton, S. A.</au><au>Rigby, A. S.</au><au>Coady, A. M.</au><au>Sandeman, D. D.</au><au>Atkin, S. L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2014-06</date><risdate>2014</risdate><volume>16</volume><issue>6</issue><spage>545</spage><epage>552</epage><pages>545-552</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><coden>DOMEF6</coden><abstract>Aim
This study investigated the effect of long‐term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS.
Methods
In this double‐blind randomized placebo‐controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo, respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 h before and after intervention.
Results
By 12 weeks, niacin/laropiprant lowered low‐density lipoprotein cholesterol (LDL‐c) (13%) and increased HDL‐c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ± 1.44 vs. 2.49 ± 1.14 mmol/l, p = 0.72). However, following the mixed meal, plasma glucose area under the response curve increased from 13.1 ± 2.9 to 14.0 ± 2.8 mmol/l, p = 0.05, as a consequence of both increased insulin resistance [HOMA‐IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02] and a reduced acute insulin response to glucose [424 (211, 975) vs. 257(122, 418) pmol/mmol, p = 0.04]. Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP.
Conclusions
In PCOS, niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased IR and reduced β‐cell function. This data may help explain why the improvement in fasting lipids has not translated into improved CV risk markers in PCOS.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>24401089</pmid><doi>10.1111/dom.12255</doi><tpages>8</tpages></addata></record> |
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| ispartof | Diabetes, obesity & metabolism, 2014-06, Vol.16 (6), p.545-552 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Beta cells Blood Glucose - drug effects Blood Glucose - metabolism Cardiovascular diseases Cardiovascular Diseases - metabolism Cholesterol Cholesterol, HDL - blood Cholesterol, LDL - blood Double-Blind Method Drug Therapy, Combination endothelial dysfunction Fasting Female Glucose Glucose metabolism High density lipoprotein Humans Hypertriglyceridemia - drug therapy Hypertriglyceridemia - metabolism Hypolipidemic Agents - administration & dosage Indoles - administration & dosage Insulin resistance Lipid metabolism Lipid Metabolism - drug effects Low density lipoprotein Niacin - administration & dosage niacin/laropiprant Nicotinic acid Placebos Polycystic ovary syndrome Polycystic Ovary Syndrome - drug therapy Polycystic Ovary Syndrome - metabolism Postprandial Period - drug effects Postprandial Period - physiology Risk Reduction Behavior Treatment Outcome Triglycerides Triglycerides - blood Vitamin B Young Adult |
| title | Postprandial effects of long-term niacin/laropiprant use on glucose and lipid metabolism and on cardiovascular risk in patients with polycystic ovary syndrome |
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