Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS

Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that...

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Published in:Journal of the American Heart Association 2019-08, Vol.8 (15), p.e012790-e012790
Main Authors: Duran, Edward K, Cook, Nancy R, Bobadilla, Maria, Kim, Eunjung, Manson, JoAnn E, Buring, Julie E, Ridker, Paul M, Pradhan, Aruna D
Format: Article
Language:English
Subjects:
angiogenesis
Cohort Studies
diabetes mellitus
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - epidemiology
Female
Humans
Middle Aged
Original Research
placenta growth factor
Placenta Growth Factor - blood
Prospective Studies
Time Factors
vascular disease
vascular growth factor
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cited_by cdi_FETCH-LOGICAL-c459t-187b9584b06459e302c7180a6b498c1413781d17fe734389af830456f33697283
cites cdi_FETCH-LOGICAL-c459t-187b9584b06459e302c7180a6b498c1413781d17fe734389af830456f33697283
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container_issue 15
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container_title Journal of the American Heart Association
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creator Duran, Edward K
Cook, Nancy R
Bobadilla, Maria
Kim, Eunjung
Manson, JoAnn E
Buring, Julie E
Ridker, Paul M
Pradhan, Aruna D
description Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case-cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15-year follow-up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5-year age groups and race. All subjects in this analysis were required to have a hemoglobin A
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Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case-cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15-year follow-up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5-year age groups and race. All subjects in this analysis were required to have a hemoglobin A &lt;6.5% at WHS enrollment. Median baseline levels of placental growth factor were higher in case subjects compare to the reference subcohort (18.0 pg/mL versus 17.2 pg/mL) but were only weakly correlated with glycemic measures and not associated with obesity. The risk of diabetes mellitus increased across placental growth factor quartile in the base model (hazard ratios, 1.00, 1.14, 1.46, and 2.14; P-trend&lt;0.001) and in multivariable-adjusted models accounting for clinical T2DM risk factors (hazard ratios, 1.00, 1.17, 1.45, and 2.61; P-trend&lt;0.001). These findings were not substantially altered by further adjustment for high-sensitivity C-reactive protein, hemoglobin A , or fasting insulin and remained robust in sensitivity analyses excluding those diagnosed within 2 years of enrollment and those with baseline hemoglobin A ≥6.0%. Conclusions Elevated placental growth factor levels are associated with future T2DM independent of traditional risk factors, measures of glycemia, insulin resistance, and high-sensitivity C-reactive protein. These prospective data suggest that pathologic angiogenesis may occur well before the clinical onset of T2DM and thus may have relevance to vascular complications of this disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.</description><identifier>ISSN: 2047-9980</identifier><identifier>EISSN: 2047-9980</identifier><identifier>DOI: 10.1161/JAHA.119.012790</identifier><identifier>PMID: 31322059</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>angiogenesis ; Cohort Studies ; diabetes mellitus ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - epidemiology ; Female ; Humans ; Middle Aged ; Original Research ; placenta growth factor ; Placenta Growth Factor - blood ; Prospective Studies ; Time Factors ; vascular disease ; vascular growth factor</subject><ispartof>Journal of the American Heart Association, 2019-08, Vol.8 (15), p.e012790-e012790</ispartof><rights>2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-187b9584b06459e302c7180a6b498c1413781d17fe734389af830456f33697283</citedby><cites>FETCH-LOGICAL-c459t-187b9584b06459e302c7180a6b498c1413781d17fe734389af830456f33697283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761678/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761678/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31322059$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Duran, Edward K</creatorcontrib><creatorcontrib>Cook, Nancy R</creatorcontrib><creatorcontrib>Bobadilla, Maria</creatorcontrib><creatorcontrib>Kim, Eunjung</creatorcontrib><creatorcontrib>Manson, JoAnn E</creatorcontrib><creatorcontrib>Buring, Julie E</creatorcontrib><creatorcontrib>Ridker, Paul M</creatorcontrib><creatorcontrib>Pradhan, Aruna D</creatorcontrib><title>Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS</title><title>Journal of the American Heart Association</title><addtitle>J Am Heart Assoc</addtitle><description>Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case-cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15-year follow-up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5-year age groups and race. All subjects in this analysis were required to have a hemoglobin A &lt;6.5% at WHS enrollment. Median baseline levels of placental growth factor were higher in case subjects compare to the reference subcohort (18.0 pg/mL versus 17.2 pg/mL) but were only weakly correlated with glycemic measures and not associated with obesity. The risk of diabetes mellitus increased across placental growth factor quartile in the base model (hazard ratios, 1.00, 1.14, 1.46, and 2.14; P-trend&lt;0.001) and in multivariable-adjusted models accounting for clinical T2DM risk factors (hazard ratios, 1.00, 1.17, 1.45, and 2.61; P-trend&lt;0.001). These findings were not substantially altered by further adjustment for high-sensitivity C-reactive protein, hemoglobin A , or fasting insulin and remained robust in sensitivity analyses excluding those diagnosed within 2 years of enrollment and those with baseline hemoglobin A ≥6.0%. Conclusions Elevated placental growth factor levels are associated with future T2DM independent of traditional risk factors, measures of glycemia, insulin resistance, and high-sensitivity C-reactive protein. These prospective data suggest that pathologic angiogenesis may occur well before the clinical onset of T2DM and thus may have relevance to vascular complications of this disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.</description><subject>angiogenesis</subject><subject>Cohort Studies</subject><subject>diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Female</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Original Research</subject><subject>placenta growth factor</subject><subject>Placenta Growth Factor - blood</subject><subject>Prospective Studies</subject><subject>Time Factors</subject><subject>vascular disease</subject><subject>vascular growth factor</subject><issn>2047-9980</issn><issn>2047-9980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVUk1P3DAQjapWBVHOvVU-9rLgj8SOe6gULSxLRQVSqThak2TCGiXx1vZuxW_on67TUAS-zHj85vnpzWTZR0ZPGJPs9Fu1rlKmTyjjStM32SGnuVpoXdK3L_KD7DiEB5qO5EoU-n12IJjgnBb6MPtz00MYgKTQ4BihJxfe_Y4bsoImOk-WbpzqHqJ1YyCVR3Le4x4ituQO-57YkVTtHhKKuI7cPm6RcHJmocaIgXxPEBt3gVyPAeMXcuNd2GIT7R7JGUQgK-8GEjdI7tY_PmTvOugDHj_Fo-zn6vx2uV5cXV9cLqurRZMXOi5YqWpdlHlNZbqjoLxRrKQg61yXDcuZUCVrmepQiVyUGrpS0LyQnRBSK16Ko-xy5m0dPJittwP4R-PAmn8F5-8N-GibHk1Hy1oITNYVbY7QQAdQANRUaZ1UQOL6OnNtd_WA7exV_4r09ctoN-be7Y1Ukkk1ifn8RODdrx2GaAYbmmQbjOh2wXAup-kWiibo6QxtkovBY_f8DaNm2ggzbUTKtJk3InV8eqnuGf9__uIvojqwrw</recordid><startdate>20190806</startdate><enddate>20190806</enddate><creator>Duran, Edward K</creator><creator>Cook, Nancy R</creator><creator>Bobadilla, Maria</creator><creator>Kim, Eunjung</creator><creator>Manson, JoAnn E</creator><creator>Buring, Julie E</creator><creator>Ridker, Paul M</creator><creator>Pradhan, Aruna D</creator><general>John Wiley and Sons Inc</general><general>Wiley</general><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><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190806</creationdate><title>Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS</title><author>Duran, Edward K ; Cook, Nancy R ; Bobadilla, Maria ; Kim, Eunjung ; Manson, JoAnn E ; Buring, Julie E ; Ridker, Paul M ; Pradhan, Aruna D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-187b9584b06459e302c7180a6b498c1413781d17fe734389af830456f33697283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>angiogenesis</topic><topic>Cohort Studies</topic><topic>diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Female</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Original Research</topic><topic>placenta growth factor</topic><topic>Placenta Growth Factor - blood</topic><topic>Prospective Studies</topic><topic>Time Factors</topic><topic>vascular disease</topic><topic>vascular growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Duran, Edward K</creatorcontrib><creatorcontrib>Cook, Nancy R</creatorcontrib><creatorcontrib>Bobadilla, Maria</creatorcontrib><creatorcontrib>Kim, Eunjung</creatorcontrib><creatorcontrib>Manson, JoAnn E</creatorcontrib><creatorcontrib>Buring, Julie E</creatorcontrib><creatorcontrib>Ridker, Paul M</creatorcontrib><creatorcontrib>Pradhan, Aruna D</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Journal of the American Heart Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Duran, Edward K</au><au>Cook, Nancy R</au><au>Bobadilla, Maria</au><au>Kim, Eunjung</au><au>Manson, JoAnn E</au><au>Buring, Julie E</au><au>Ridker, Paul M</au><au>Pradhan, Aruna D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS</atitle><jtitle>Journal of the American Heart Association</jtitle><addtitle>J Am Heart Assoc</addtitle><date>2019-08-06</date><risdate>2019</risdate><volume>8</volume><issue>15</issue><spage>e012790</spage><epage>e012790</epage><pages>e012790-e012790</pages><issn>2047-9980</issn><eissn>2047-9980</eissn><abstract>Background Pathologic angiogenesis is a hallmark of type 2 diabetes mellitus (T2DM) microvascular complications and may modulate adipogenesis and precede the onset of clinical diabetes mellitus; however, longitudinal data are unavailable. Placental growth factor is a potent proangiogenic factor that stimulates the formation of mature and durable vessels but is understudied in human diseases. Methods and Results We conducted a prospective case-cohort study of baseline placental growth factor and incident T2DM within the WHS (Women's Health Study). A random sample of incident T2DM cases (n=491) occurring over a 15-year follow-up period was selected and compared with a reference subcohort (n=561). Case subjects were matched to the reference risk set on 5-year age groups and race. All subjects in this analysis were required to have a hemoglobin A &lt;6.5% at WHS enrollment. Median baseline levels of placental growth factor were higher in case subjects compare to the reference subcohort (18.0 pg/mL versus 17.2 pg/mL) but were only weakly correlated with glycemic measures and not associated with obesity. The risk of diabetes mellitus increased across placental growth factor quartile in the base model (hazard ratios, 1.00, 1.14, 1.46, and 2.14; P-trend&lt;0.001) and in multivariable-adjusted models accounting for clinical T2DM risk factors (hazard ratios, 1.00, 1.17, 1.45, and 2.61; P-trend&lt;0.001). These findings were not substantially altered by further adjustment for high-sensitivity C-reactive protein, hemoglobin A , or fasting insulin and remained robust in sensitivity analyses excluding those diagnosed within 2 years of enrollment and those with baseline hemoglobin A ≥6.0%. Conclusions Elevated placental growth factor levels are associated with future T2DM independent of traditional risk factors, measures of glycemia, insulin resistance, and high-sensitivity C-reactive protein. These prospective data suggest that pathologic angiogenesis may occur well before the clinical onset of T2DM and thus may have relevance to vascular complications of this disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.</abstract><cop>England</cop><pub>John Wiley and Sons Inc</pub><pmid>31322059</pmid><doi>10.1161/JAHA.119.012790</doi><oa>free_for_read</oa></addata></record>
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subjects angiogenesis
Cohort Studies
diabetes mellitus
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - epidemiology
Female
Humans
Middle Aged
Original Research
placenta growth factor
Placenta Growth Factor - blood
Prospective Studies
Time Factors
vascular disease
vascular growth factor
title Plasma Placental Growth Factor Concentrations Are Elevated Well in Advance of Type 2 Diabetes Mellitus Onset: Prospective Data From the WHS
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