AIM/HYPOTHESIS Hepatic insulin resistance (HIR) is considered to be an independent predictor of metabolic disorders and plays an important role in systemic inflammation, which contributes to abnormalities in cardiovascular disease (CVD) risk factors. The aim of this study was to investigate the relationship between HIR and new markers of cardiovascular risks, including leptin/adiponectin ratio (L/A), lipoprotein(a) [Lp(a)], and tumor necrosis factor alpha (TNF-α), at comparable whole body insulin sensitivity in non-diabetic individuals with or without CVD and at high risk of developing type 2 diabetes. METHODS The HIR index, L/A, Lp(a), and TNF-α were measured in 50 participants with CVD and in 200 without CVD (1:4 ratio). These were also matched for the homeostatic model assessment for insulin resistance (HOMA-IR) and Matsuda-insulin sensitivity index (ISI) in an observational study design. RESULTS The HIR index (1.52 ± 0.14 vs. 1.45 ± 0.17, p < 0.02), L/A (3.22 ± 3.10 vs. 2.09 ± 2.27, p < 0.004), and levels of Lp(a) (66.6 ± 49.5 vs. 37.9 ± 3 6.8 mg/dL, p < 0.0001) and TNF-α (18.9 ± 21.8 vs. 5.4 ± 7.1 pg/mL, p < 0.0001) were higher in those with CVD than those without CVD. HOMA-IR and ISI were not significantly different (p = 0.88 and p = 0.35, respectively). The HIR index was directly correlated with L/A (r = 0.41, p < 0.0001), Lp(a) (r = 0.20, p < 0.002), TNF- α (r = 0.14, p < 0.03), and diastolic blood pressure (DBP) (r = 0.13, p < 0.03). The stepwise model analysis showed that L/A, Lp(a), and TNF-α explained about 20% of the variation in the HIR indices of all the participants (p < 0.02). CONCLUSIONS/INTERPRETATIONS Our results suggest a positive association between HIR and new markers of cardiovascular risk [L/A, Lp(a), and TNF- α] at comparable whole body insulin sensitivity in those with or without CVD and at high risk of developing type 2 diabetes.

中文翻译：

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心血管风险新标志物与 2 型糖尿病高危人群肝脏胰岛素抵抗之间的关联。

目的/假设 肝胰岛素抵抗 (HIR) 被认为是代谢紊乱的独立预测因子，在全身炎症中起重要作用，导致心血管疾病 (CVD) 危险因素的异常。本研究的目的是调查 HIR 与心血管风险新标志物之间的关系，包括瘦素/脂联素比率 (L/A)、脂蛋白 (a) [Lp(a)] 和肿瘤坏死因子 α (TNF-α) )，在有或没有心血管疾病的非糖尿病个体中具有相当的全身胰岛素敏感性，并且患 2 型糖尿病的风险很高。方法 对 50 名 CVD 参与者和 200 名非 CVD 参与者（比例为 1:4）测量 HIR 指数、L/A、Lp(a) 和 TNF-α。在一项观察性研究设计中，这些也与胰岛素抵抗 (HOMA-IR) 和松田-胰岛素敏感性指数 (ISI) 的稳态模型评估相匹配。结果 HIR 指数 (1.52 ± 0.14 vs. 1.45 ± 0.17, p < 0.02)、L/A (3.22 ± 3.10 vs. 2.09 ± 2.27, p < 0.004) 和 Lp(a) 水平 (66.6 ± 49.5 vs. CVD 患者的 37.9 ± 3 6.8 mg/dL, p < 0.0001) 和 TNF-α (18.9 ± 21.8 vs. 5.4 ± 7.1 pg/mL, p < 0.0001) 高于非 CVD 患者。HOMA-IR 和 ISI 没有显着差异（分别为 p = 0.88 和 p = 0.35）。HIR 指数与 L/A (r = 0.41, p < 0.0001)、Lp(a) (r = 0.20, p < 0.002)、TNF-α (r = 0.14, p < 0.03) 和舒张血量直接相关压力 (DBP) (r = 0.13, p < 0.03)。逐步模型分析表明，L/A、Lp(a)、和 TNF-α 解释了所有参与者 HIR 指数变化的约 20% (p < 0.02)。结论/解释 我们的研究结果表明，在有或没有 CVD 和高发病风险的人群中，HIR 与心血管风险的新标志物 [L/A、Lp(a) 和 TNF-α] 之间存在可比的全身胰岛素敏感性。 2型糖尿病。