Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance
Context: Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. Objective: The objective of the study was to investigate whether insulin sensitivity and insulin’s effects on the...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2008-09, Vol.93 (9), p.3365-3372 |
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| creator | Ketel, Iris J. G. Stehouwer, Coen D. A. Serné, Erik H. Korsen, Ted J. M. Hompes, Peter G. A. Smulders, Yvo M. de Jongh, Renate T. Homburg, Roy Lambalk, Cornelis B. |
| description | Context: Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity.
Objective: The objective of the study was to investigate whether insulin sensitivity and insulin’s effects on the microcirculation are impaired in normal-weight and obese women with PCOS.
Design and Population: Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia.
Main Outcome Measures: Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity).
Results: Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups.
Conclusion: PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases. |
| doi_str_mv | 10.1210/jc.2008-0626 |
| format | Article |
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Objective: The objective of the study was to investigate whether insulin sensitivity and insulin’s effects on the microcirculation are impaired in normal-weight and obese women with PCOS.
Design and Population: Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia.
Main Outcome Measures: Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity).
Results: Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups.
Conclusion: PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2008-0626</identifier><identifier>PMID: 18593766</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Biological and medical sciences ; Blood Pressure - drug effects ; Blood Vessels - drug effects ; Blood Vessels - physiology ; Body Weight - physiology ; Endocrinopathies ; Endothelium, Vascular - drug effects ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Insulin - administration & dosage ; Insulin - pharmacology ; Insulin Resistance - physiology ; Medical sciences ; Nitroprusside - pharmacology ; Obesity - complications ; Obesity - metabolism ; Obesity - physiopathology ; Polycystic Ovary Syndrome - complications ; Polycystic Ovary Syndrome - metabolism ; Polycystic Ovary Syndrome - physiopathology ; Skin - blood supply ; Skin - drug effects ; Vasodilation - drug effects ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2008-09, Vol.93 (9), p.3365-3372</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-8e58f52e6891ef396ff1ca26ece07e9180d046bad7e641a11499e794afb93a4b3</citedby><cites>FETCH-LOGICAL-c401t-8e58f52e6891ef396ff1ca26ece07e9180d046bad7e641a11499e794afb93a4b3</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=20628700$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18593766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ketel, Iris J. G.</creatorcontrib><creatorcontrib>Stehouwer, Coen D. A.</creatorcontrib><creatorcontrib>Serné, Erik H.</creatorcontrib><creatorcontrib>Korsen, Ted J. M.</creatorcontrib><creatorcontrib>Hompes, Peter G. A.</creatorcontrib><creatorcontrib>Smulders, Yvo M.</creatorcontrib><creatorcontrib>de Jongh, Renate T.</creatorcontrib><creatorcontrib>Homburg, Roy</creatorcontrib><creatorcontrib>Lambalk, Cornelis B.</creatorcontrib><title>Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity.
Objective: The objective of the study was to investigate whether insulin sensitivity and insulin’s effects on the microcirculation are impaired in normal-weight and obese women with PCOS.
Design and Population: Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia.
Main Outcome Measures: Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity).
Results: Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups.
Conclusion: PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Blood Vessels - drug effects</subject><subject>Blood Vessels - physiology</subject><subject>Body Weight - physiology</subject><subject>Endocrinopathies</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - pharmacology</subject><subject>Insulin Resistance - physiology</subject><subject>Medical sciences</subject><subject>Nitroprusside - pharmacology</subject><subject>Obesity - complications</subject><subject>Obesity - metabolism</subject><subject>Obesity - physiopathology</subject><subject>Polycystic Ovary Syndrome - complications</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Polycystic Ovary Syndrome - physiopathology</subject><subject>Skin - blood supply</subject><subject>Skin - drug effects</subject><subject>Vasodilation - drug effects</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkD2P1DAQhi0E4paDjhq5gYoctuPYcXms-DjpjkV86Ogsx5mwXiX2YjuHQs0Px6tdQUMxmmIevTPzIPSUkgvKKHm1sxeMkLYigol7aEUVbypJlbyPVoQwWinJvp2hRyntCKGcN_VDdEbbRtVSiBX6vekgAX49Z_whHCpOZqxuwX3fZnwbJvD4p8tb_DGMi11SdhZv7kxc8OfF97HM8WUEvN6aaGyG6H5Bj7sF30A2XRgLbXyPb5yN4c4kO48m4iuf5tF5_AmSS9l4C4_Rg8GMCZ6c-jn6-vbNl_X76nrz7mp9eV1ZTmiuWmjaoWEgWkVhqJUYBmoNE2CBSFC0JT3hojO9BMGpoZQrBVJxM3SqNryrz9GLY-4-hh8zpKwnlyyMo_EQ5qSFahiphSzgyyNY7k4pwqD30U3lbU2JPljXO6sP1vXBesGfnXLnboL-H3zSXIDnJ6BIMOMQy9cu_eVYSWklIYWrjxz4PtjoPOwjpKR3YY6-mPn_-j8atZ0-</recordid><startdate>20080901</startdate><enddate>20080901</enddate><creator>Ketel, Iris J. G.</creator><creator>Stehouwer, Coen D. A.</creator><creator>Serné, Erik H.</creator><creator>Korsen, Ted J. M.</creator><creator>Hompes, Peter G. A.</creator><creator>Smulders, Yvo M.</creator><creator>de Jongh, Renate T.</creator><creator>Homburg, Roy</creator><creator>Lambalk, Cornelis B.</creator><general>Endocrine Society</general><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>7X8</scope></search><sort><creationdate>20080901</creationdate><title>Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance</title><author>Ketel, Iris J. G. ; Stehouwer, Coen D. A. ; Serné, Erik H. ; Korsen, Ted J. M. ; Hompes, Peter G. A. ; Smulders, Yvo M. ; de Jongh, Renate T. ; Homburg, Roy ; Lambalk, Cornelis B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-8e58f52e6891ef396ff1ca26ece07e9180d046bad7e641a11499e794afb93a4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Blood Vessels - drug effects</topic><topic>Blood Vessels - physiology</topic><topic>Body Weight - physiology</topic><topic>Endocrinopathies</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - pharmacology</topic><topic>Insulin Resistance - physiology</topic><topic>Medical sciences</topic><topic>Nitroprusside - pharmacology</topic><topic>Obesity - complications</topic><topic>Obesity - metabolism</topic><topic>Obesity - physiopathology</topic><topic>Polycystic Ovary Syndrome - complications</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Polycystic Ovary Syndrome - physiopathology</topic><topic>Skin - blood supply</topic><topic>Skin - drug effects</topic><topic>Vasodilation - drug effects</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ketel, Iris J. G.</creatorcontrib><creatorcontrib>Stehouwer, Coen D. A.</creatorcontrib><creatorcontrib>Serné, Erik H.</creatorcontrib><creatorcontrib>Korsen, Ted J. M.</creatorcontrib><creatorcontrib>Hompes, Peter G. A.</creatorcontrib><creatorcontrib>Smulders, Yvo M.</creatorcontrib><creatorcontrib>de Jongh, Renate T.</creatorcontrib><creatorcontrib>Homburg, Roy</creatorcontrib><creatorcontrib>Lambalk, Cornelis B.</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ketel, Iris J. G.</au><au>Stehouwer, Coen D. A.</au><au>Serné, Erik H.</au><au>Korsen, Ted J. M.</au><au>Hompes, Peter G. A.</au><au>Smulders, Yvo M.</au><au>de Jongh, Renate T.</au><au>Homburg, Roy</au><au>Lambalk, Cornelis B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2008-09-01</date><risdate>2008</risdate><volume>93</volume><issue>9</issue><spage>3365</spage><epage>3372</epage><pages>3365-3372</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity.
Objective: The objective of the study was to investigate whether insulin sensitivity and insulin’s effects on the microcirculation are impaired in normal-weight and obese women with PCOS.
Design and Population: Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia.
Main Outcome Measures: Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity).
Results: Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups.
Conclusion: PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>18593766</pmid><doi>10.1210/jc.2008-0626</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The journal of clinical endocrinology and metabolism, 2008-09, Vol.93 (9), p.3365-3372 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Biological and medical sciences Blood Pressure - drug effects Blood Vessels - drug effects Blood Vessels - physiology Body Weight - physiology Endocrinopathies Endothelium, Vascular - drug effects Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Humans Insulin - administration & dosage Insulin - pharmacology Insulin Resistance - physiology Medical sciences Nitroprusside - pharmacology Obesity - complications Obesity - metabolism Obesity - physiopathology Polycystic Ovary Syndrome - complications Polycystic Ovary Syndrome - metabolism Polycystic Ovary Syndrome - physiopathology Skin - blood supply Skin - drug effects Vasodilation - drug effects Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology |
| title | Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance |
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