Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; MD/PhD (PECEM) Program, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; División de Investigación, Instituto Nacional de Geriatría, Mexico City, Mexico.
Nutr Metab Cardiovasc Dis. 2021 Feb 8;31(2):506-517. doi: 10.1016/j.numecd.2020.09.031. Epub 2020 Oct 15.
Both insulin resistance (IR) and visceral adipose tissue (VAT) are related cardiometabolic risk factors; nevertheless, their joint effect on endothelial functionality is controversial. This study aims to evaluate the joint effect of IR and VAT on endothelial functionality using the pulse-waveform analysis and explore the mediating role of VAT on the effect of IR on arterial pressure, arterial stiffness and incident arterial hypertension.
We measured VAT (n = 586) using two methods (dual-energy X-ray absorptiometry and a clinical surrogate), arterial stiffness (with pulse-waveform velocity), and IR (using three methods: HOMA2-IR (n = 586), a frequently sampled intravenous glucose tolerance test (n = 131) and euglycemic hyperinsulinemic clamping (n = 97)) to confirm the mediator effect of IR on VAT. The incidence of arterial hypertension attributable to the mediating effect of IR related to VAT was evaluated using a prospective cohort (n = 6850). Adjusted linear regression models, causal mediation analysis, and Cox-proportional hazard risk regression models were performed to test our objective. IR and VAT led to increased arterial stiffness and increased blood pressure; the combination of both further worsened vascular parameters. Nearly, 57% (Δ 95% CI: 31.7-100.0) of the effect of IR on altered pulse-wave velocity (PWV) analysis was mediated through VAT. Moreover, VAT acts as a mediator of the effect of IR on increased mean arterial pressure (Δ 35.7%, 95% CI: 23.8-59) and increased hypertension risk (Δ 69.1%, 95% CI: 46.1-78.8).
VAT acts as a mediator of IR in promoting arterial stiffness and arterial hypertension. Both phenomena should be targeted to ameliorate the cardiometabolic risk.
胰岛素抵抗（IR）和内脏脂肪组织（VAT）均与心血管代谢风险因素有关；然而，它们对内皮功能的联合影响仍存在争议。本研究旨在使用脉搏波分析评估 IR 和 VAT 对内皮功能的联合影响，并探讨 VAT 对 IR 对动脉压、动脉僵硬和动脉高血压发生的影响的中介作用。
我们使用两种方法（双能 X 射线吸收法和临床替代法）测量了 VAT（n=586），使用三种方法测量了动脉僵硬（使用脉搏波速度）和 IR（使用 HOMA2-IR（n=586）、频繁采样静脉葡萄糖耐量试验（n=131）和正葡萄糖高胰岛素钳夹（n=97））来确认 IR 对 VAT 的中介作用。使用前瞻性队列（n=6850）评估归因于与 VAT 相关的 IR 中介作用的动脉高血压的发生率。进行了调整线性回归模型、因果中介分析和 Cox 比例风险回归模型来检验我们的目标。IR 和 VAT 导致动脉僵硬和血压升高；两者的组合进一步恶化了血管参数。IR 对改变脉搏波速度（PWV）分析的影响约有 57%（Δ95%CI：31.7-100.0）通过 VAT 介导。此外，VAT 是 IR 对平均动脉压升高（Δ35.7%，95%CI：23.8-59）和高血压风险增加（Δ69.1%，95%CI：46.1-78.8）的影响的中介物。
VAT 是 IR 促进动脉僵硬和动脉高血压的中介物。两种现象都应该作为改善心血管代谢风险的目标。
