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抗逆转录病毒疗法诱导的人类免疫缺陷病毒1型患者胰岛素抵抗和氧化性脱氧核糖核酸损伤

Antiretroviral Therapy-induced Insulin Resistance and Oxidative Deoxy Nucleic Acid Damage in Human Immunodeficiency Virus-1 Patients.

作者信息

Honnapurmath Vaishali Kolgiri, Patil V W

机构信息

Department of Biochemistry, Grant Government Medical College and Sir J J Groups of Hospitals, Mumbai, Maharashtra, India.

出版信息

Indian J Endocrinol Metab. 2017 Mar-Apr;21(2):316-321. doi: 10.4103/2230-8210.202029.

Abstract

BACKGROUND AND OBJECTIVES

Insulin resistance (IR) is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy (ART). Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1-infected patients with different ART status.

MATERIALS AND METHODS

In this case-control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment.

RESULTS

All subjects were randomly selected and grouped as HIV-negative (control group) ( = 300), HIV-positive without ART ( = 100), HIV-positive with ART first line ( = 100), and HIV-positive with ART second line ( = 100). IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595-3.509) < 0.001.

INTERPRETATION AND CONCLUSIONS

In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

摘要

背景与目的

胰岛素抵抗(IR)在人类免疫缺陷病毒(HIV)感染中很常见,且可能与抗逆转录病毒疗法(ART)有关。氧化应激参数增加和羰基蛋白与胰岛素敏感性相关。本研究旨在确定不同ART状态的HIV-1感染患者的IR及其与氧化脱氧核糖核酸(DNA)损伤的关联。

材料与方法

在这项病例对照研究中,共纳入600名受试者。我们使用氧化碱基8-羟基-2'-脱氧鸟苷(8-OHdG)的血浆水平作为氧化DNA损伤的生物标志物。使用高灵敏度的8-OHdG检测酶联免疫吸附测定试剂盒测量8-OHdG。使用稳态模型评估来确定IR。

结果

所有受试者均随机选取并分为HIV阴性(对照组)(n = 300)、未接受ART的HIV阳性(n = 100)、接受一线ART的HIV阳性(n = 100)和接受二线ART的HIV阳性(n = 100)。接受二线ART的HIV阳性患者和接受一线ART的HIV阳性患者的IR和氧化DNA损伤显著高于未接受ART的患者。在线性回归分析中,IR增加与DNA损伤增加呈正相关(优势比:3.052,95%置信区间:2.595 - 3.509)P < 0.001。

解读与结论

在本研究中,我们观察到ART在接受ART的HIV阳性患者IR和氧化DNA损伤的发生中起重要作用。在为HIV/AIDS患者开ART处方时,了解这些生物标志物可能对临床医生有帮助。需要进行更大规模的研究以确定ART在诱导IR和DNA损伤中的确切作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6151/5367237/342621b2c250/IJEM-21-316-g002.jpg

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