@article{d1b490c024034c5ca0a97bf6323e4332,
title = "Elevated CD4+T-cell glucose metabolism in HIV+ women with diabetes mellitus",
abstract = "Objective:Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4+T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4+T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4+T-cell glucose metabolism in HIV+ women with and without diabetes mellitus.Design:A case-control study was used to compare CD4+T-cell glucose metabolism in women with HIV with or without diabetes mellitus.Methods:Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4+cell count. CD4+T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4+T cells.Results:HIV+DM+ displayed a significantly elevated proportion of CD4+T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- (P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4+T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4+T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-.Conclusion:CD4+T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4+T-cell metabolic dysfunction.",
keywords = "CD4T cells, HIV, diabetes mellitus, immunometabolism",
author = "Butterfield, {Tiffany R.} and Hanna, {David B.} and Kaplan, {Robert C.} and Xiaonan Xue and Kizer, {Jorge R.} and Durkin, {Helen G.} and Kassaye, {Seble G.} and Marek Nowicki and Tien, {Phyllis C.} and Topper, {Elizabeth T.} and Floris-Moore, {Michelle A.} and Kehmia Titanji and Fischl, {Margaret A.} and Sonya Heath and Palmer, {Clovis S.} and Landay, {Alan L.} and Anzinger, {Joshua J.}",
note = "Funding Information: This work was supported in part by Alan Landay [UM1 AI106701] and Office of the Principal of the University of the West Indies, Mona. Robert Kaplan is supported by 1R01HL148094 and 1R01HL140976 (NHLBI). Data in this manuscript were collected by the Women's Interagency HIV Study, now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): [Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D'Souza, Stephen Gange and Elizabeth Golub), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, and Deborah Konkle-Parker), U01-HL146192; UNC CRS (Adaora Adimora), U01-HL146194]. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1-TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30-AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), and P30-MH-116867 (Miami CHARM). D.B.H. was supported by K01-HL-137557. Funding Information: As a Global Infectious Diseases Scholar, T.B. received mentored research training in the development of this manuscript. This training was supported in part by the University at Buffalo Clinical and Translational Science Institute award UL1TR001412 and the Global Infectious Diseases Research Training Program award D43TW010919. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Clinical and Translational Science Institute or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",
year = "2022",
month = aug,
day = "1",
doi = "10.1097/QAD.0000000000003272",
language = "English (US)",
volume = "36",
pages = "1327--1336",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "10",
}
