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T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus

Abstract Background A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus...

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Published in:The Journal of infectious diseases 2020-06, Vol.222 (2), p.252-262
Main Authors: Bailin, Samuel S, McGinnis, Kathleen A, McDonnell, Wyatt J, So-Armah, Kaku, Wellons, Melissa, Tracy, Russell P, Doyle, Margaret F, Mallal, Simon, Justice, Amy C, Freiberg, Matthew S, Landay, Alan L, Wanjalla, Celestine, Koethe, John R
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container_title The Journal of infectious diseases
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creator Bailin, Samuel S
McGinnis, Kathleen A
McDonnell, Wyatt J
So-Armah, Kaku
Wellons, Melissa
Tracy, Russell P
Doyle, Margaret F
Mallal, Simon
Justice, Amy C
Freiberg, Matthew S
Landay, Alan L
Wanjalla, Celestine
Koethe, John R
description Abstract Background A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH). Methods Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent diabetes cases were adjudicated by 2 physicians for PWH and HIV-negative participants in the Veterans Aging Cohort Study. Multivariable logistic regression models evaluated the association of T-cell subsets and diabetes stratified by HIV status, adjusted for cytomegalovirus serostatus and traditional risk factors. Results Among 2385 participants (65% PWH, 95% male, 68% African American), higher CD45RO+ memory CD4+ T cells and lower CD38+ CD4+ T cells were associated with prevalent diabetes, and had a similar effect size, in both the PWH and HIV-negative (P ≤ .05 for all). Lower CD38+CD8+ T cells were also associated with diabetes in both groups. Conclusions The CD4+ and CD8+ T-cell subsets associated with diabetes are similar in PWH and HIV-negative individuals, suggesting that diabetes in PWH may be related to chronic immune activation. T-cell alterations, including memory CD4+ T-cell expansion, are associated with diabetes in both persons with HIV and HIV-negative individuals, suggesting that changes to the T-cell compartment is related to or possibly mediates diabetes in persons with HIV.
doi_str_mv 10.1093/infdis/jiaa069
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Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH). Methods Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent diabetes cases were adjudicated by 2 physicians for PWH and HIV-negative participants in the Veterans Aging Cohort Study. Multivariable logistic regression models evaluated the association of T-cell subsets and diabetes stratified by HIV status, adjusted for cytomegalovirus serostatus and traditional risk factors. Results Among 2385 participants (65% PWH, 95% male, 68% African American), higher CD45RO+ memory CD4+ T cells and lower CD38+ CD4+ T cells were associated with prevalent diabetes, and had a similar effect size, in both the PWH and HIV-negative (P ≤ .05 for all). Lower CD38+CD8+ T cells were also associated with diabetes in both groups. Conclusions The CD4+ and CD8+ T-cell subsets associated with diabetes are similar in PWH and HIV-negative individuals, suggesting that diabetes in PWH may be related to chronic immune activation. T-cell alterations, including memory CD4+ T-cell expansion, are associated with diabetes in both persons with HIV and HIV-negative individuals, suggesting that changes to the T-cell compartment is related to or possibly mediates diabetes in persons with HIV.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiaa069</identifier><identifier>PMID: 32052044</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adaptive immunity ; Aging ; Biomarkers - blood ; CD38 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cohort Studies ; Cross-Sectional Studies ; Diabetes ; Diabetes Complications ; Diabetes mellitus ; Diabetes Mellitus - immunology ; Female ; Flow cytometry ; HIV ; HIV Infections - complications ; HIV Infections - immunology ; Human immunodeficiency virus ; Humans ; Immunologic Memory ; Immunological memory ; Lymphocytes ; Lymphocytes T ; Major and Brief Reports ; Male ; Memory cells ; Middle Aged ; Regression Analysis ; Risk factors ; T-Lymphocyte Subsets - immunology ; Veterans</subject><ispartof>The Journal of infectious diseases, 2020-06, Vol.222 (2), p.252-262</ispartof><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-563b6f24acfd8f0ab1aded9ed4bc5e5b8ade9d0af752ba11d7cd8781bc4e64d43</citedby><cites>FETCH-LOGICAL-c452t-563b6f24acfd8f0ab1aded9ed4bc5e5b8ade9d0af752ba11d7cd8781bc4e64d43</cites><orcidid>0000-0001-6490-6942 ; 0000-0003-0139-5502 ; 0000-0003-4990-1013</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27900,27901</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32052044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bailin, Samuel S</creatorcontrib><creatorcontrib>McGinnis, Kathleen A</creatorcontrib><creatorcontrib>McDonnell, Wyatt J</creatorcontrib><creatorcontrib>So-Armah, Kaku</creatorcontrib><creatorcontrib>Wellons, Melissa</creatorcontrib><creatorcontrib>Tracy, Russell P</creatorcontrib><creatorcontrib>Doyle, Margaret F</creatorcontrib><creatorcontrib>Mallal, Simon</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Freiberg, Matthew S</creatorcontrib><creatorcontrib>Landay, Alan L</creatorcontrib><creatorcontrib>Wanjalla, Celestine</creatorcontrib><creatorcontrib>Koethe, John R</creatorcontrib><title>T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract Background A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH). Methods Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent diabetes cases were adjudicated by 2 physicians for PWH and HIV-negative participants in the Veterans Aging Cohort Study. Multivariable logistic regression models evaluated the association of T-cell subsets and diabetes stratified by HIV status, adjusted for cytomegalovirus serostatus and traditional risk factors. Results Among 2385 participants (65% PWH, 95% male, 68% African American), higher CD45RO+ memory CD4+ T cells and lower CD38+ CD4+ T cells were associated with prevalent diabetes, and had a similar effect size, in both the PWH and HIV-negative (P ≤ .05 for all). Lower CD38+CD8+ T cells were also associated with diabetes in both groups. Conclusions The CD4+ and CD8+ T-cell subsets associated with diabetes are similar in PWH and HIV-negative individuals, suggesting that diabetes in PWH may be related to chronic immune activation. T-cell alterations, including memory CD4+ T-cell expansion, are associated with diabetes in both persons with HIV and HIV-negative individuals, suggesting that changes to the T-cell compartment is related to or possibly mediates diabetes in persons with HIV.</description><subject>Adaptive immunity</subject><subject>Aging</subject><subject>Biomarkers - blood</subject><subject>CD38 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes</subject><subject>Diabetes Complications</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - immunology</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - immunology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Major and Brief Reports</subject><subject>Male</subject><subject>Memory cells</subject><subject>Middle Aged</subject><subject>Regression Analysis</subject><subject>Risk factors</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>Veterans</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqFkctrFTEUh4Mo9lrdupSAG11Mm9c8shFKfbRwQcFalyGTnPHmMpPcJpPC_e-bMtdS3XSVhPPl45zzQ-gtJSeUSH7q_GBdOt06rUkjn6EVrXlbNQ3lz9GKEMYq2kl5hF6ltCWECN60L9ERZ6RmRIgVurnC6_202wSznwH_zH2COeGzlIJxegaLf7t5g39EuNUj-Bl_drqHGRJ2Hl-XS9Q-LYz2CxzyjC_ypD2-nKbsg4XBGQfe7PG1izm9Ri8GPSZ4cziP0a-vX67OL6r192-X52fryoiazVXd8L4ZmNBmsN1AdE-1BSvBit7UUPddeUpL9NDWrNeU2tbYru1obwQ0wgp-jD4t3l3uJ7CmdB_1qHbRTTruVdBO_VvxbqP-hFvVcsaFlEXw4SCI4SZDmtXkkoFx1B5CTorxWrS8bLou6Pv_0G3I0ZfxFBNCUiaLsVAnC2ViSCnC8NAMJeo-TbWkqQ5plg_vHo_wgP-NrwAfFyDk3VOyOwQ5r3c</recordid><startdate>20200629</startdate><enddate>20200629</enddate><creator>Bailin, Samuel S</creator><creator>McGinnis, Kathleen A</creator><creator>McDonnell, Wyatt J</creator><creator>So-Armah, Kaku</creator><creator>Wellons, Melissa</creator><creator>Tracy, Russell P</creator><creator>Doyle, Margaret F</creator><creator>Mallal, Simon</creator><creator>Justice, Amy C</creator><creator>Freiberg, Matthew S</creator><creator>Landay, Alan L</creator><creator>Wanjalla, Celestine</creator><creator>Koethe, John R</creator><general>Oxford University Press</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6490-6942</orcidid><orcidid>https://orcid.org/0000-0003-0139-5502</orcidid><orcidid>https://orcid.org/0000-0003-4990-1013</orcidid></search><sort><creationdate>20200629</creationdate><title>T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus</title><author>Bailin, Samuel S ; McGinnis, Kathleen A ; McDonnell, Wyatt J ; So-Armah, Kaku ; Wellons, Melissa ; Tracy, Russell P ; Doyle, Margaret F ; Mallal, Simon ; Justice, Amy C ; Freiberg, Matthew S ; Landay, Alan L ; Wanjalla, Celestine ; Koethe, John R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-563b6f24acfd8f0ab1aded9ed4bc5e5b8ade9d0af752ba11d7cd8781bc4e64d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adaptive immunity</topic><topic>Aging</topic><topic>Biomarkers - blood</topic><topic>CD38 antigen</topic><topic>CD4 antigen</topic><topic>CD4 Lymphocyte Count</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes</topic><topic>Diabetes Complications</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - immunology</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - immunology</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunologic Memory</topic><topic>Immunological memory</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Major and Brief Reports</topic><topic>Male</topic><topic>Memory cells</topic><topic>Middle Aged</topic><topic>Regression Analysis</topic><topic>Risk factors</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>Veterans</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bailin, Samuel S</creatorcontrib><creatorcontrib>McGinnis, Kathleen A</creatorcontrib><creatorcontrib>McDonnell, Wyatt J</creatorcontrib><creatorcontrib>So-Armah, Kaku</creatorcontrib><creatorcontrib>Wellons, Melissa</creatorcontrib><creatorcontrib>Tracy, Russell P</creatorcontrib><creatorcontrib>Doyle, Margaret F</creatorcontrib><creatorcontrib>Mallal, Simon</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Freiberg, Matthew S</creatorcontrib><creatorcontrib>Landay, Alan L</creatorcontrib><creatorcontrib>Wanjalla, Celestine</creatorcontrib><creatorcontrib>Koethe, John R</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 Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bailin, Samuel S</au><au>McGinnis, Kathleen A</au><au>McDonnell, Wyatt J</au><au>So-Armah, Kaku</au><au>Wellons, Melissa</au><au>Tracy, Russell P</au><au>Doyle, Margaret F</au><au>Mallal, Simon</au><au>Justice, Amy C</au><au>Freiberg, Matthew S</au><au>Landay, Alan L</au><au>Wanjalla, Celestine</au><au>Koethe, John R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2020-06-29</date><risdate>2020</risdate><volume>222</volume><issue>2</issue><spage>252</spage><epage>262</epage><pages>252-262</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><abstract>Abstract Background A higher proportion of circulating memory CD4+ T cells is associated with prevalent diabetes mellitus in the general population. Given the broad changes in adaptive immunity, including memory T-cell expansion, and rising prevalence of diabetes in the human immunodeficiency virus (HIV) population, we assessed whether similar relationships were present in persons with HIV (PWH). Methods Multiple CD4+ and CD8+ T-cell subsets were measured by flow cytometry, and prevalent diabetes cases were adjudicated by 2 physicians for PWH and HIV-negative participants in the Veterans Aging Cohort Study. Multivariable logistic regression models evaluated the association of T-cell subsets and diabetes stratified by HIV status, adjusted for cytomegalovirus serostatus and traditional risk factors. Results Among 2385 participants (65% PWH, 95% male, 68% African American), higher CD45RO+ memory CD4+ T cells and lower CD38+ CD4+ T cells were associated with prevalent diabetes, and had a similar effect size, in both the PWH and HIV-negative (P ≤ .05 for all). Lower CD38+CD8+ T cells were also associated with diabetes in both groups. Conclusions The CD4+ and CD8+ T-cell subsets associated with diabetes are similar in PWH and HIV-negative individuals, suggesting that diabetes in PWH may be related to chronic immune activation. T-cell alterations, including memory CD4+ T-cell expansion, are associated with diabetes in both persons with HIV and HIV-negative individuals, suggesting that changes to the T-cell compartment is related to or possibly mediates diabetes in persons with HIV.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32052044</pmid><doi>10.1093/infdis/jiaa069</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-6490-6942</orcidid><orcidid>https://orcid.org/0000-0003-0139-5502</orcidid><orcidid>https://orcid.org/0000-0003-4990-1013</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adaptive immunity
Aging
Biomarkers - blood
CD38 antigen
CD4 antigen
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cohort Studies
Cross-Sectional Studies
Diabetes
Diabetes Complications
Diabetes mellitus
Diabetes Mellitus - immunology
Female
Flow cytometry
HIV
HIV Infections - complications
HIV Infections - immunology
Human immunodeficiency virus
Humans
Immunologic Memory
Immunological memory
Lymphocytes
Lymphocytes T
Major and Brief Reports
Male
Memory cells
Middle Aged
Regression Analysis
Risk factors
T-Lymphocyte Subsets - immunology
Veterans
title T Lymphocyte Subsets Associated With Prevalent Diabetes in Veterans With and Without Human Immunodeficiency Virus
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