The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial)
The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics. All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. p...
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| creator | Kolb, Hubert Lückemeyer, Kathrin Heise, Tim Herder, Christian Schloot, Nanette C Koenig, Wolfgang Heinemann, Lutz Martin, Stephan |
| description | The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.
All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p |
| doi_str_mv | 10.1371/journal.pone.0072440 |
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All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.
In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.
ClinicalTrials.gov registration number: NCT00974740.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0072440</identifier><identifier>PMID: 23991111</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute phase proteins ; Acute phase substances ; Adhesion ; Adolescent ; Adult ; Age ; Atherosclerosis ; Atorvastatin ; Autoantibodies ; Beta cells ; Biology ; Body mass ; Chemokines ; Correlation ; Cytokines ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 1 - immunology ; Drugs ; E-selectin ; Fasting ; Female ; Humans ; Inflammation ; Insulin ; Interleukin ; Interleukin 1 ; Interleukin 1 receptor antagonist ; Interleukin 1 Receptor Antagonist Protein - physiology ; Interleukin 1 receptors ; Interleukin 6 ; IP (Internet Protocol) ; IP-10 protein ; Islets of Langerhans - immunology ; Lymphocytes T ; Male ; Medicine ; Metabolic syndrome ; Obesity ; Patients ; Peptides ; Proteins ; Recruitment ; Rodents ; Sex ; Young Adult ; γ-Interferon</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e72440-e72440</ispartof><rights>2013 Kolb et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Kolb et al 2013 Kolb et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-4cb13508cea44d6c086d2aa28b9d41fd2437244f48fe7acdccbeed1762368d153</citedby><cites>FETCH-LOGICAL-c526t-4cb13508cea44d6c086d2aa28b9d41fd2437244f48fe7acdccbeed1762368d153</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/PMC3753272/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753272/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23991111$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kolb, Hubert</creatorcontrib><creatorcontrib>Lückemeyer, Kathrin</creatorcontrib><creatorcontrib>Heise, Tim</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Schloot, Nanette C</creatorcontrib><creatorcontrib>Koenig, Wolfgang</creatorcontrib><creatorcontrib>Heinemann, Lutz</creatorcontrib><creatorcontrib>Martin, Stephan</creatorcontrib><creatorcontrib>DIATOR Study Group</creatorcontrib><creatorcontrib>on behalf of the DIATOR Study Group</creatorcontrib><title>The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.
All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.
In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.
ClinicalTrials.gov registration number: NCT00974740.</description><subject>Acute phase proteins</subject><subject>Acute phase substances</subject><subject>Adhesion</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Atherosclerosis</subject><subject>Atorvastatin</subject><subject>Autoantibodies</subject><subject>Beta cells</subject><subject>Biology</subject><subject>Body mass</subject><subject>Chemokines</subject><subject>Correlation</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Drugs</subject><subject>E-selectin</subject><subject>Fasting</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Interleukin</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 Receptor Antagonist Protein - physiology</subject><subject>Interleukin 1 receptors</subject><subject>Interleukin 6</subject><subject>IP (Internet Protocol)</subject><subject>IP-10 protein</subject><subject>Islets of Langerhans - immunology</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Medicine</subject><subject>Metabolic syndrome</subject><subject>Obesity</subject><subject>Patients</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Recruitment</subject><subject>Rodents</subject><subject>Sex</subject><subject>Young Adult</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUjRCIPuAPEFhiUxYZ_IqTsECqymukSpXQsLYc-2bqaWKntkM1C_6dzExatQhvbPmec-49VyfL3hC8IKwkHzd-DE51i8E7WGBcUs7xs-yY1IzmgmL2_NH7KDuJcYNxwSohXmZHlNU1mc5x9md1DShuY4LeamT7fnSAHKQ7H26QdSiABpeQdxESStsBEEHGqgYSxE9oVwuqQ8F3gHw7ERKEDsYb63Ky5w7JB6RcUmvvbEzo7MvyfHX1E62CVd2HV9mLVnURXs_3afbr29fVxY_88ur78uL8MtcFFSnnuiGswJUGxbkRGlfCUKVo1dSGk9ZQznb2W161UCpttG4ADCkFZaIypGCn2buD7tD5KOfNRUk4rbDArGITYnlAGK82cgi2V2ErvbJy_-HDWqqQrO5ACl6QxmAwbdVwXuKqKEtSc2iaEqjAZNL6PHcbmx7MvKQnok8rzl7Ltf8tWVkwWtJJ4GwWCP52hJhkb6OGrlMO_Lifu6akwIRP0Pf_QP_vjh9QOvgYA7QPwxAsd2m6Z8ldmuScpon29rGRB9J9fNhfkAHI6A</recordid><startdate>20130826</startdate><enddate>20130826</enddate><creator>Kolb, Hubert</creator><creator>Lückemeyer, Kathrin</creator><creator>Heise, Tim</creator><creator>Herder, Christian</creator><creator>Schloot, Nanette C</creator><creator>Koenig, Wolfgang</creator><creator>Heinemann, Lutz</creator><creator>Martin, Stephan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130826</creationdate><title>The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial)</title><author>Kolb, Hubert ; Lückemeyer, Kathrin ; Heise, Tim ; Herder, Christian ; Schloot, Nanette C ; Koenig, Wolfgang ; Heinemann, Lutz ; Martin, Stephan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-4cb13508cea44d6c086d2aa28b9d41fd2437244f48fe7acdccbeed1762368d153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute phase proteins</topic><topic>Acute phase substances</topic><topic>Adhesion</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Atherosclerosis</topic><topic>Atorvastatin</topic><topic>Autoantibodies</topic><topic>Beta cells</topic><topic>Biology</topic><topic>Body mass</topic><topic>Chemokines</topic><topic>Correlation</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Drugs</topic><topic>E-selectin</topic><topic>Fasting</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Interleukin</topic><topic>Interleukin 1</topic><topic>Interleukin 1 receptor antagonist</topic><topic>Interleukin 1 Receptor Antagonist Protein - physiology</topic><topic>Interleukin 1 receptors</topic><topic>Interleukin 6</topic><topic>IP (Internet Protocol)</topic><topic>IP-10 protein</topic><topic>Islets of Langerhans - immunology</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Medicine</topic><topic>Metabolic syndrome</topic><topic>Obesity</topic><topic>Patients</topic><topic>Peptides</topic><topic>Proteins</topic><topic>Recruitment</topic><topic>Rodents</topic><topic>Sex</topic><topic>Young Adult</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kolb, Hubert</creatorcontrib><creatorcontrib>Lückemeyer, Kathrin</creatorcontrib><creatorcontrib>Heise, Tim</creatorcontrib><creatorcontrib>Herder, Christian</creatorcontrib><creatorcontrib>Schloot, Nanette C</creatorcontrib><creatorcontrib>Koenig, Wolfgang</creatorcontrib><creatorcontrib>Heinemann, Lutz</creatorcontrib><creatorcontrib>Martin, Stephan</creatorcontrib><creatorcontrib>DIATOR Study Group</creatorcontrib><creatorcontrib>on behalf of the DIATOR Study Group</creatorcontrib><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>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kolb, Hubert</au><au>Lückemeyer, Kathrin</au><au>Heise, Tim</au><au>Herder, Christian</au><au>Schloot, Nanette C</au><au>Koenig, Wolfgang</au><au>Heinemann, Lutz</au><au>Martin, Stephan</au><aucorp>DIATOR Study Group</aucorp><aucorp>on behalf of the DIATOR Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-26</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e72440</spage><epage>e72440</epage><pages>e72440-e72440</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.
All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.
In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.
ClinicalTrials.gov registration number: NCT00974740.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23991111</pmid><doi>10.1371/journal.pone.0072440</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-08, Vol.8 (8), p.e72440-e72440 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acute phase proteins Acute phase substances Adhesion Adolescent Adult Age Atherosclerosis Atorvastatin Autoantibodies Beta cells Biology Body mass Chemokines Correlation Cytokines Diabetes Diabetes mellitus Diabetes Mellitus, Type 1 - immunology Drugs E-selectin Fasting Female Humans Inflammation Insulin Interleukin Interleukin 1 Interleukin 1 receptor antagonist Interleukin 1 Receptor Antagonist Protein - physiology Interleukin 1 receptors Interleukin 6 IP (Internet Protocol) IP-10 protein Islets of Langerhans - immunology Lymphocytes T Male Medicine Metabolic syndrome Obesity Patients Peptides Proteins Recruitment Rodents Sex Young Adult γ-Interferon |
| title | The systemic immune network in recent onset type 1 diabetes: central role of interleukin-1 receptor antagonist (DIATOR Trial) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T22%3A18%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20systemic%20immune%20network%20in%20recent%20onset%20type%201%20diabetes:%20central%20role%20of%20interleukin-1%20receptor%20antagonist%20(DIATOR%20Trial)&rft.jtitle=PloS%20one&rft.au=Kolb,%20Hubert&rft.aucorp=DIATOR%20Study%20Group&rft.date=2013-08-26&rft.volume=8&rft.issue=8&rft.spage=e72440&rft.epage=e72440&rft.pages=e72440-e72440&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0072440&rft_dat=%3Cproquest_plos_%3E1429215014%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428060383&rft_id=info:pmid/23991111&rft_doaj_id=oai_doaj_org_article_6451bd0edf8b44708577194ebb7e2601&rfr_iscdi=true |