Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes
Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes Christian Pfleger 1 , Henrik B. Mortensen 2 , Lars Hansen 3 , Christian Herder 1 , Bart O. Roep 4 , Hillary Hoey 5 , Henk-Jan Aanstoot 6 , Mirjana Kocova 7 , Nanette C. Schloot 1 8 and on behalf of th...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2008-04, Vol.57 (4), p.929-937 |
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| container_title | Diabetes (New York, N.Y.) |
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| creator | PFLEGER, Christian MORTENSEN, Henrik B HANSEN, Lars HERDER, Christian ROEP, Bart O HOEY, Hillary AANSTOOT, Henk-Jan KOCOVA, Mirjana SCHLOOT, Nanette C |
| description | Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes
Christian Pfleger 1 ,
Henrik B. Mortensen 2 ,
Lars Hansen 3 ,
Christian Herder 1 ,
Bart O. Roep 4 ,
Hillary Hoey 5 ,
Henk-Jan Aanstoot 6 ,
Mirjana Kocova 7 ,
Nanette C. Schloot 1 8 and
on behalf of the Hvidøre Study Group on Childhood Diabetes
1 Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf,
Düsseldorf, Germany
2 Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark
3 Development Projects, Novo Nordisk A/S, Bagsværd, Denmark
4 Department of Immunohaematology and Blood and Transfusion, Leiden University Medical Center, Leiden, the Netherlands
5 University of Dublin, National Children’s Hospital, Tallaght, Ireland
6 Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, the Netherlands
7 Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia
8 Centre for Internal Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Address correspondence and reprint requests to Christian Pfleger, Institute for Clinical Diabetes Research at German Diabetes
Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail:
ch.pfleger{at}web.de
Abstract
OBJECTIVE— We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin,
proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical
remission in patients with recent-onset type 1 diabetes.
RESEARCH DESIGN AND METHODS— Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide,
blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after
diagnosis. Analyses were adjusted for sex, age, and BMI percentile.
RESULTS— Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 ( P = 0.0009) and 12 ( P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of
IL-1β with C-peptide after 1 month ( P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12
months ( P < 0.05) and positively correlated with A1C after 1 |
| doi_str_mv | 10.2337/db07-1697 |
| format | Article |
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Christian Pfleger 1 ,
Henrik B. Mortensen 2 ,
Lars Hansen 3 ,
Christian Herder 1 ,
Bart O. Roep 4 ,
Hillary Hoey 5 ,
Henk-Jan Aanstoot 6 ,
Mirjana Kocova 7 ,
Nanette C. Schloot 1 8 and
on behalf of the Hvidøre Study Group on Childhood Diabetes
1 Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf,
Düsseldorf, Germany
2 Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark
3 Development Projects, Novo Nordisk A/S, Bagsværd, Denmark
4 Department of Immunohaematology and Blood and Transfusion, Leiden University Medical Center, Leiden, the Netherlands
5 University of Dublin, National Children’s Hospital, Tallaght, Ireland
6 Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, the Netherlands
7 Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia
8 Centre for Internal Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Address correspondence and reprint requests to Christian Pfleger, Institute for Clinical Diabetes Research at German Diabetes
Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail:
ch.pfleger{at}web.de
Abstract
OBJECTIVE— We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin,
proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical
remission in patients with recent-onset type 1 diabetes.
RESEARCH DESIGN AND METHODS— Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide,
blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after
diagnosis. Analyses were adjusted for sex, age, and BMI percentile.
RESULTS— Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 ( P = 0.0009) and 12 ( P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of
IL-1β with C-peptide after 1 month ( P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12
months ( P < 0.05) and positively correlated with A1C after 1 month ( P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month ( P = 0.009) and showed a positive association with blood glucose disposal after 12 months ( P = 0.047).
CONCLUSIONS— IL-1ra is associated with preserved β-cell capacity in type 1 diabetes. This novel finding indicates that administration of
IL-1ra, successfully improving β-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes.
The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models
into the human situation in vivo.
IL, interleukin
TNF, tumor necrosis factor
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 25 February 2008. DOI: 10.2337/db07-1697.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1697 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 18, 2008.
Received December 3, 2007.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db07-1697</identifier><identifier>PMID: 18299313</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adiponectin - blood ; Adolescent ; Biological and medical sciences ; Blood Glucose - metabolism ; Body fat ; C-Peptide - blood ; Cell death ; Child ; Child, Preschool ; Cytokines ; Cytokines - blood ; Diabetes ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 2 - blood ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Glucose ; Glycated Hemoglobin A - metabolism ; Health aspects ; Humans ; Infant ; Insulin resistance ; Interleukin-1 ; Interleukin-1 Receptor Accessory Protein - blood ; Longitudinal Studies ; Male ; Medical sciences ; Metabolism ; Peptides ; Physiological aspects ; Protein hormones ; Remission (Medicine) ; Research design ; Tumor necrosis factor-TNF ; Type 1 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2008-04, Vol.57 (4), p.929-937</ispartof><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 American Diabetes Association</rights><rights>Copyright American Diabetes Association Apr 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-fd4e326151e45176a257bfb72f4d2a7664ece288c7e890166e112221ff861cf23</citedby><cites>FETCH-LOGICAL-c587t-fd4e326151e45176a257bfb72f4d2a7664ece288c7e890166e112221ff861cf23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20228096$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18299313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PFLEGER, Christian</creatorcontrib><creatorcontrib>MORTENSEN, Henrik B</creatorcontrib><creatorcontrib>HANSEN, Lars</creatorcontrib><creatorcontrib>HERDER, Christian</creatorcontrib><creatorcontrib>ROEP, Bart O</creatorcontrib><creatorcontrib>HOEY, Hillary</creatorcontrib><creatorcontrib>AANSTOOT, Henk-Jan</creatorcontrib><creatorcontrib>KOCOVA, Mirjana</creatorcontrib><creatorcontrib>SCHLOOT, Nanette C</creatorcontrib><creatorcontrib>Hvidøre Study Group on Childhood Diabetes</creatorcontrib><creatorcontrib>on behalf of the Hvidøre Study Group on Childhood Diabetes</creatorcontrib><title>Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes
Christian Pfleger 1 ,
Henrik B. Mortensen 2 ,
Lars Hansen 3 ,
Christian Herder 1 ,
Bart O. Roep 4 ,
Hillary Hoey 5 ,
Henk-Jan Aanstoot 6 ,
Mirjana Kocova 7 ,
Nanette C. Schloot 1 8 and
on behalf of the Hvidøre Study Group on Childhood Diabetes
1 Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf,
Düsseldorf, Germany
2 Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark
3 Development Projects, Novo Nordisk A/S, Bagsværd, Denmark
4 Department of Immunohaematology and Blood and Transfusion, Leiden University Medical Center, Leiden, the Netherlands
5 University of Dublin, National Children’s Hospital, Tallaght, Ireland
6 Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, the Netherlands
7 Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia
8 Centre for Internal Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Address correspondence and reprint requests to Christian Pfleger, Institute for Clinical Diabetes Research at German Diabetes
Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail:
ch.pfleger{at}web.de
Abstract
OBJECTIVE— We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin,
proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical
remission in patients with recent-onset type 1 diabetes.
RESEARCH DESIGN AND METHODS— Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide,
blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after
diagnosis. Analyses were adjusted for sex, age, and BMI percentile.
RESULTS— Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 ( P = 0.0009) and 12 ( P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of
IL-1β with C-peptide after 1 month ( P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12
months ( P < 0.05) and positively correlated with A1C after 1 month ( P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month ( P = 0.009) and showed a positive association with blood glucose disposal after 12 months ( P = 0.047).
CONCLUSIONS— IL-1ra is associated with preserved β-cell capacity in type 1 diabetes. This novel finding indicates that administration of
IL-1ra, successfully improving β-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes.
The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models
into the human situation in vivo.
IL, interleukin
TNF, tumor necrosis factor
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 25 February 2008. DOI: 10.2337/db07-1697.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1697 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 18, 2008.
Received December 3, 2007.
DIABETES</description><subject>Adiponectin - blood</subject><subject>Adolescent</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - metabolism</subject><subject>Body fat</subject><subject>C-Peptide - blood</subject><subject>Cell death</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - blood</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>Glucose</subject><subject>Glycated Hemoglobin A - metabolism</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant</subject><subject>Insulin resistance</subject><subject>Interleukin-1</subject><subject>Interleukin-1 Receptor Accessory Protein - blood</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Peptides</subject><subject>Physiological aspects</subject><subject>Protein hormones</subject><subject>Remission (Medicine)</subject><subject>Research design</subject><subject>Tumor necrosis factor-TNF</subject><subject>Type 1 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp90lGL1DAQB_AiireePvgFpCgKCj0zaZs0j8uq58HCHXKibyFNJ90c3bYmKXrf3tQtHieL5KEl-c0wDP8keQ7kjOY5f9_UhGfABH-QrEDkIssp__4wWRECNAMu-EnyxPsbQgiL53FyAhUVIod8lei194O2KtihTweTXmwzcCpVfZOuGzsOPepg-_SbDbt0k13hGGyDf56_4N56P5fF96vYAPvgD_D6dsQU0g9W1RjQP00eGdV5fLZ8T5Ovnz5ebz5n28vzi816m-my4iEzTYE5ZVACFiVwpmjJa1NzaoqGKs5YgRppVWmOlSDAGAJQSsGYioE2ND9N3hz6jm74MaEPMk6osetUj8PkJSdFwVkBEb78B94Mk-vjbJICK6qSExLRqwNqVYfS9mYITum5o1wD55wC5SKq7IhqsUenurg9Y-P1PX92xMfTxHXqowVv7xVEE_BXaNXkvazOt_8bZrF66DpsUcZlby6P9tZu8N6hkaOze-VuJRA5J0vOyZJzsqJ9sexsqvfY3MklShG8XoDyWnXGqV5b_9dRQmlFBIvu3cHtbLv7aR3KZsnJ3U_JZSEFFflvvjrdtA</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>PFLEGER, Christian</creator><creator>MORTENSEN, Henrik B</creator><creator>HANSEN, Lars</creator><creator>HERDER, Christian</creator><creator>ROEP, Bart O</creator><creator>HOEY, Hillary</creator><creator>AANSTOOT, Henk-Jan</creator><creator>KOCOVA, Mirjana</creator><creator>SCHLOOT, Nanette C</creator><general>American Diabetes Association</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>8GL</scope><scope>3V.</scope><scope>7RV</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>AZQEC</scope><scope>BBNVY</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>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</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><scope>7X8</scope></search><sort><creationdate>20080401</creationdate><title>Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes</title><author>PFLEGER, Christian ; MORTENSEN, Henrik B ; HANSEN, Lars ; HERDER, Christian ; ROEP, Bart O ; HOEY, Hillary ; AANSTOOT, Henk-Jan ; KOCOVA, Mirjana ; SCHLOOT, Nanette C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-fd4e326151e45176a257bfb72f4d2a7664ece288c7e890166e112221ff861cf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adiponectin - blood</topic><topic>Adolescent</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - metabolism</topic><topic>Body fat</topic><topic>C-Peptide - blood</topic><topic>Cell death</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 1 - blood</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>Glucose</topic><topic>Glycated Hemoglobin A - metabolism</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Infant</topic><topic>Insulin resistance</topic><topic>Interleukin-1</topic><topic>Interleukin-1 Receptor Accessory Protein - blood</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Peptides</topic><topic>Physiological aspects</topic><topic>Protein hormones</topic><topic>Remission (Medicine)</topic><topic>Research design</topic><topic>Tumor necrosis factor-TNF</topic><topic>Type 1 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PFLEGER, Christian</creatorcontrib><creatorcontrib>MORTENSEN, Henrik B</creatorcontrib><creatorcontrib>HANSEN, Lars</creatorcontrib><creatorcontrib>HERDER, Christian</creatorcontrib><creatorcontrib>ROEP, Bart O</creatorcontrib><creatorcontrib>HOEY, Hillary</creatorcontrib><creatorcontrib>AANSTOOT, Henk-Jan</creatorcontrib><creatorcontrib>KOCOVA, Mirjana</creatorcontrib><creatorcontrib>SCHLOOT, Nanette C</creatorcontrib><creatorcontrib>Hvidøre Study Group on Childhood Diabetes</creatorcontrib><creatorcontrib>on behalf of the Hvidøre Study Group on Childhood Diabetes</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>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PFLEGER, Christian</au><au>MORTENSEN, Henrik B</au><au>HANSEN, Lars</au><au>HERDER, Christian</au><au>ROEP, Bart O</au><au>HOEY, Hillary</au><au>AANSTOOT, Henk-Jan</au><au>KOCOVA, Mirjana</au><au>SCHLOOT, Nanette C</au><aucorp>Hvidøre Study Group on Childhood Diabetes</aucorp><aucorp>on behalf of the Hvidøre Study Group on Childhood Diabetes</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>57</volume><issue>4</issue><spage>929</spage><epage>937</epage><pages>929-937</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes
Christian Pfleger 1 ,
Henrik B. Mortensen 2 ,
Lars Hansen 3 ,
Christian Herder 1 ,
Bart O. Roep 4 ,
Hillary Hoey 5 ,
Henk-Jan Aanstoot 6 ,
Mirjana Kocova 7 ,
Nanette C. Schloot 1 8 and
on behalf of the Hvidøre Study Group on Childhood Diabetes
1 Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf,
Düsseldorf, Germany
2 Department of Paediatrics, Glostrup University Hospital, Glostrup, Denmark
3 Development Projects, Novo Nordisk A/S, Bagsværd, Denmark
4 Department of Immunohaematology and Blood and Transfusion, Leiden University Medical Center, Leiden, the Netherlands
5 University of Dublin, National Children’s Hospital, Tallaght, Ireland
6 Diabetes Center for Pediatric and Adolescent Diabetes Care and Research, Rotterdam, the Netherlands
7 Paediatric Clinic, Department of Endocrinology and Genetics, Skopje, Republic of Macedonia
8 Centre for Internal Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Address correspondence and reprint requests to Christian Pfleger, Institute for Clinical Diabetes Research at German Diabetes
Centre, Leibniz Institute at Heinrich-Heine-University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail:
ch.pfleger{at}web.de
Abstract
OBJECTIVE— We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin,
proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical
remission in patients with recent-onset type 1 diabetes.
RESEARCH DESIGN AND METHODS— Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide,
blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after
diagnosis. Analyses were adjusted for sex, age, and BMI percentile.
RESULTS— Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 ( P = 0.0009) and 12 ( P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of
IL-1β with C-peptide after 1 month ( P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12
months ( P < 0.05) and positively correlated with A1C after 1 month ( P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month ( P = 0.009) and showed a positive association with blood glucose disposal after 12 months ( P = 0.047).
CONCLUSIONS— IL-1ra is associated with preserved β-cell capacity in type 1 diabetes. This novel finding indicates that administration of
IL-1ra, successfully improving β-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes.
The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models
into the human situation in vivo.
IL, interleukin
TNF, tumor necrosis factor
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 25 February 2008. DOI: 10.2337/db07-1697.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1697 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 18, 2008.
Received December 3, 2007.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>18299313</pmid><doi>10.2337/db07-1697</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2008-04, Vol.57 (4), p.929-937 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_proquest_journals_216485700 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adiponectin - blood Adolescent Biological and medical sciences Blood Glucose - metabolism Body fat C-Peptide - blood Cell death Child Child, Preschool Cytokines Cytokines - blood Diabetes Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 2 - blood Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Glucose Glycated Hemoglobin A - metabolism Health aspects Humans Infant Insulin resistance Interleukin-1 Interleukin-1 Receptor Accessory Protein - blood Longitudinal Studies Male Medical sciences Metabolism Peptides Physiological aspects Protein hormones Remission (Medicine) Research design Tumor necrosis factor-TNF Type 1 diabetes |
| title | Association of IL-1ra and Adiponectin With C-Peptide and Remission in Patients With Type 1 Diabetes |
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