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We previously reported that DM risk was greater in women of African ancestry with HIV who had mitochondrial DNA (mtDNA) haplogroup L3. We examined haplogroup associations with DM and selected soluble and cellular immune biomarkers among people with HIV (PWH) and those without HIV in the Veterans Aging Cohort Study (VACS) Biomarker Cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>VACS participants had mtDNA haplogroups determined from genome-wide genotyping and adjudicated DM outcomes. Serum interleukin 6, D-dimer, and soluble CD14 were quantified, and cellular phenotyping was performed by flow cytometry, on blood collected during 2005\u20132007. Analyses included logistic and Cox regression of prevalent and incident DM, stratified by self-reported ancestry and HIV status, and adjusted for selected covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>mtDNA haplogroups, soluble and\/or cellular biomarkers, and DM outcomes were available for 2019 participants (65% with HIV; 68% non-Hispanic Black; 95% male). Among 781 Black PWH, mtDNA haplogroup L3 (40%) was associated with incident DM (hazard ratio, 1.56 [95% confidence interval, 1.01\u20132.40]) adjusting for covariates including senescent (CD28\u2013) CD4+ T cells, which were lower in Black PWH having haplogroup L3 versus other African haplogroups (P = .05). No other haplogroups were associated with DM. There were no significant associations observed in Veterans without HIV, although the effect size was similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>mtDNA haplogroup L3 was associated with incident DM in predominantly male non-Hispanic Black PWH, replicating an association reported previously. This haplogroup was associated with fewer senescent CD4+ T cells, but the association with DM was independent of T-cell phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf304","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T07:54:56Z","timestamp":1749196496000},"page":"e1003-e1011","source":"Crossref","is-referenced-by-count":3,"title":["Mitochondrial DNA Haplogroups, Biomarkers of Inflammation and Immune Activation, and Risk of Diabetes in Veterans With and Without Human Immunodeficiency Virus"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-6786","authenticated-orcid":false,"given":"Aiwei","family":"Yan","sequence":"first","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Kundu","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Samuels","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4990-1013","authenticated-orcid":false,"given":"Samuel","family":"Bailin","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Yale University Schools of Medicine and Public Health , West Haven, Connecticut ,","place":["USA"]},{"name":"Veterans Affairs Connecticut Healthcare System , West Haven, Connecticut ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-6384","authenticated-orcid":false,"given":"Kaku","family":"So-Armah","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeel A","family":"Butt","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College , New York, New York ,","place":["USA"]},{"name":"Veterans Affairs Pittsburgh Healthcare System , Pittsburgh, Pennsylvania ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Gerschenson","sequence":"additional","affiliation":[{"name":"John A. Burns School of Medicine, University of Hawaii\u2013Manoa , Honolulu, Hawaii ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew Bidwell","family":"Goetz","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System , Los Angeles, California ,","place":["USA"]},{"name":"David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Doyle","sequence":"additional","affiliation":[{"name":"Lerner College of Medicine, University of Vermont , Burlington, Vermont ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Tracy","sequence":"additional","affiliation":[{"name":"Lerner College of Medicine, University of Vermont , Burlington, Vermont ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent C","family":"Marconi","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Rollins School of Public Health , Atlanta, Georgia ,","place":["USA"]},{"name":"Atlanta Veterans Affairs Medical Center , Atlanta, Georgia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-5502","authenticated-orcid":false,"given":"Amy","family":"Justice","sequence":"additional","affiliation":[{"name":"Yale University Schools of Medicine and Public Health , West Haven, Connecticut ,","place":["USA"]},{"name":"Veterans Affairs Connecticut Healthcare System , West Haven, Connecticut ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6490-6942","authenticated-orcid":false,"given":"John R","family":"Koethe","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]},{"name":"Veterans Affairs Tennessee Valley Healthcare System , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-067X","authenticated-orcid":false,"given":"Todd","family":"Hulgan","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center , Nashville, Tennessee ,","place":["USA"]},{"name":"Veterans Affairs Tennessee Valley Healthcare System , Nashville, Tennessee ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"2026031304472402900_jiaf304-B1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4172\/2155-6156.1000732","article-title":"The effect of HIV and art on the development of hypertension and type 2 diabetes mellitus","volume":"8","author":"Maseko","year":"2017","journal-title":"J Diabetes Metab"},{"key":"2026031304472402900_jiaf304-B2","doi-asserted-by":"crossref","first-page":"S383","DOI":"10.1093\/infdis\/jis205","article-title":"Body composition and metabolic changes in HIV-infected patients","volume":"205(Suppl 3)","author":"Stanley","year":"2012","journal-title":"J Infect Dis"},{"key":"2026031304472402900_jiaf304-B3","doi-asserted-by":"crossref","first-page":"e0194199","DOI":"10.1371\/journal.pone.0194199","article-title":"Type 2 diabetes prevalence and its risk factors in HIV: a cross-sectional study","volume":"13","author":"Duncan","year":"2018","journal-title":"PLoS One"},{"key":"2026031304472402900_jiaf304-B4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/978-94-007-2869-1_10","article-title":"Mitochondria and diabetes. 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