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已发表论文
HIV 感染与胰岛素抵抗、糖尿病之间不存在遗传因果关系：一项双向孟德尔随机化分析
Received 12 June 2025
Accepted for publication 18 September 2025
Published 30 September 2025 Volume 2025:18 Pages 6205—6218
DOI https://doi.org/10.2147/JMDH.S546669
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Scott Fraser
Pengfei Liu,1 Qiurong Zeng2
1Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
Correspondence: Pengfei Liu, Email lpfei01@163.com
Background: The causal relationship between HIV infection and insulin resistance, as well as diabetes mellitus, remains uncertain. This study explores these associations using genome-wide association study data and Mendelian randomization techniques.
Methods: We performed bidirectional, two-sample Mendelian randomization analyses to evaluate the causal links between HIV infection and insulin resistance, as well as type 1 diabetes, type 2 diabetes, and gestational diabetes. Additionally, we assessed the relationship between HIV infection and glycated hemoglobin. Five Mendelian randomization methods were employed: inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. Cochran’s Q test was used to assess heterogeneity, while the MR-Egger intercept test evaluated horizontal pleiotropy. Sensitivity was evaluated using the leave-one-out method.
Results: No causal effects were found between HIV infection and insulin resistance, type 1 diabetes, type 2 diabetes, gestational diabetes, or HbA1c levels. IVW analysis and other Mendelian randomization methods consistently yielded null results (all p > 0.05). Reverse Mendelian randomization analyses supported these null findings. Sensitivity analyses confirmed the robustness of our results, with no significant heterogeneity or pleiotropy detected.
Conclusion: This Mendelian randomization study found no significant causal links between HIV infection and insulin resistance or diabetes mellitus. The null association with glycated hemoglobin further supports these findings. These results provide insights into the pathogenesis of insulin resistance and diabetes in individuals living with HIV, highlighting the need for further exploration of potential mediating factors, such as antiretroviral therapy, inflammation, and obesity.
Keywords: HIV infection, insulin resistance, diabetes, Mendelian randomization study, mediating factors
1Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
Correspondence: Pengfei Liu, Email lpfei01@163.com
Background: The causal relationship between HIV infection and insulin resistance, as well as diabetes mellitus, remains uncertain. This study explores these associations using genome-wide association study data and Mendelian randomization techniques.
Methods: We performed bidirectional, two-sample Mendelian randomization analyses to evaluate the causal links between HIV infection and insulin resistance, as well as type 1 diabetes, type 2 diabetes, and gestational diabetes. Additionally, we assessed the relationship between HIV infection and glycated hemoglobin. Five Mendelian randomization methods were employed: inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. Cochran’s Q test was used to assess heterogeneity, while the MR-Egger intercept test evaluated horizontal pleiotropy. Sensitivity was evaluated using the leave-one-out method.
Results: No causal effects were found between HIV infection and insulin resistance, type 1 diabetes, type 2 diabetes, gestational diabetes, or HbA1c levels. IVW analysis and other Mendelian randomization methods consistently yielded null results (all p > 0.05). Reverse Mendelian randomization analyses supported these null findings. Sensitivity analyses confirmed the robustness of our results, with no significant heterogeneity or pleiotropy detected.
Conclusion: This Mendelian randomization study found no significant causal links between HIV infection and insulin resistance or diabetes mellitus. The null association with glycated hemoglobin further supports these findings. These results provide insights into the pathogenesis of insulin resistance and diabetes in individuals living with HIV, highlighting the need for further exploration of potential mediating factors, such as antiretroviral therapy, inflammation, and obesity.
Keywords: HIV infection, insulin resistance, diabetes, Mendelian randomization study, mediating factors