Department of Microbiology, University of the West Indies - Mona, Kingston.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
AIDS. 2022 Aug 1;36(10):1327-1336. doi: 10.1097/QAD.0000000000003272. Epub 2022 Jun 21.
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.
A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus.
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.
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-.
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.
免疫功能障碍和慢性炎症是 HIV 感染和糖尿病的特征，CD4+T 细胞代谢与这两种疾病的发病机制有关。然而，关于 HIV 合并糖尿病患者的 CD4+T 细胞代谢，信息有限。我们检测了 HIV 阳性且患有或未患有糖尿病的女性的 CD4+T 细胞葡萄糖代谢情况。
采用病例对照研究比较了 HIV 阳性且无糖尿病（HIV+DM-，N=20）或 2 型糖尿病 HIV 阳性女性（HIV+DM+，N=16）或有（HIV+DMTx+，N=18）抗糖尿病治疗的女性的 CD4+T 细胞葡萄糖代谢情况。
从 WIHS 中确定了非糖尿病（HIV+DM-，N=20）或 2 型糖尿病 HIV 阳性女性（HIV+DM+，N=16）或无（HIV+DMTx+，N=18）抗糖尿病治疗的女性，并按年龄、种族/民族、吸烟状况和 CD4+细胞计数进行匹配。通过流式细胞术、代谢基因的微流体 qRT-PCR 和刺激后的 CD4+T 细胞的 Seahorse 细胞外通量分析，检查 CD4+T 细胞免疫代谢情况。
HIV+DM+的 CD4+T 细胞表达免疫代谢标志物 GLUT1 的比例明显高于 HIV+DMTx+和 HIV+DM-（P=0.04 和 P=0.01）。与 HIV+DMTx+相比，HIV+DM+的 CD4+T 细胞中编码葡萄糖代谢途径关键酶的基因表达升高。与 HIV+DM-相比，HIV+DM+的 TCR 激活的 CD4+T 细胞的糖酵解和氧化磷酸化水平升高。
HIV+DM+的 CD4+T 细胞的葡萄糖代谢增加。治疗 HIV 女性的糖尿病可能部分纠正 CD4+T 细胞代谢功能障碍。
