No Genetic Causal Relationship Between HIV Infection and Insulin Resistance, Diabetes: A Bidirectional Mendelian Randomization Analysis.

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.