Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women.
Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women.
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DOI：
10.1210/jcem.86.3.7305
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发表时间：
2001-03
期刊：
影响因子：
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通讯作者：
J. Fernández-Real;M. Vayreda;C. Richart;C. Gutiérrez;M. Broch;J. Vendrell;W. Ricart
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文献类型：
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作者：
J. Fernández-Real;M. Vayreda;C. Richart;C. Gutiérrez;M. Broch;J. Vendrell;W. Ricart
越来越多的证据表明，全身炎症和胰岛素抵抗构成了导致动脉粥样硬化的相互关联的事件。我们在228名健康志愿者中研究了循环白细胞介素6（IL-6）水平（炎症的主要介质之一）和C反应蛋白对胰岛素抵抗和血压的影响。所有受试者的血浆IL-6浓度与收缩压（SBP）和舒张压（DBP）、空腹胰岛素和空腹胰岛素抵抗指数（FIRI）均显著相关。当从分析中排除吸烟者时，血浆IL-6水平与脂肪质量百分比（r = 0.19; P = 0.02）、绝对脂肪质量（r = 0.17; P = 0.03）、SBP、DBP、空腹胰岛素水平和FIRI相关。在控制体重指数后，后者的相关性持续存在（SBP和DBP分别为r = 0.15和r = 0.19; P = 0.02和P = 0.0004;空腹胰岛素和FIRI分别为r = 0.24和r = 0.19，P = 0.004和P = 0.03）。性别和吸烟状况显着影响结果。虽然IL-6水平与男性空腹胰岛素和FIRI显著相关，但在女性中未观察到这些显著相关性。相反，虽然IL-6水平与女性SBP和DBP显著相关，但这些系数在男性中无统计学意义。所有这些关联在吸烟者中都消失了，而在非吸烟者中仍然很明显。由于IL-6是肝细胞急性期反应的主要介质，并诱导C-反应蛋白（CRP）的合成，我们还控制了后者。所有受试者的血清CRP水平与IL-6显著相关，但主要在非吸烟者和男性中。值得注意的是，这种重要的关系在吸烟者中消失了。CRP与空腹胰岛素（r = 0.28; P < 0.0001）和FIRI（r = 0.25; P < 0.0001）相关，但与SBP或DBP无关（P = NS）。与IL-6不同，CRP与这些参数之间的关联在男性和女性以及吸烟者和非吸烟者中相似。对于胰岛素和FIRI，它们在女性和非吸烟者中更强。CPR与WHR仅在男性中显著相关（r = 0.22; P = 0.01）。使用多元线性回归逐步预测循环IL-6水平，吸烟状况（P = 0.0059）和FIRI（P = 0.03），但不是脂肪量或SBP，独立贡献了11%的变异在男性。当CRP被引入模型时，后者（P < 0.0001）和吸烟状态（P = 0.02），而不是FIRI，脂肪量或SBP，导致IL-6水平变异的33%。在女性中，只有SBP（P = 0.04）贡献了5%的方差。当CRP被引入模型中时，同样只有SBP（P = 0.01）对IL-6水平的方差贡献了10%。其中25名受试者的胰岛素敏感性采用频繁采样的静脉葡萄糖耐量试验和最小模型分析确定，循环IL-6水平与胰岛素敏感性指数密切相关（r = -0.65，P < 0.0001）。同样，这种关系在男性中更强（r = -0.75; P < 0.001），在女性中不显著（r = -0.26; P = NS）。在所有这些受试者中，只有胰岛素敏感性（P = 0.0037），而不是脂肪质量，在多元线性回归分析中贡献了IL-6水平方差的21%。总之，循环中的IL-6水平，通过诱导女性高血压或男性胰岛素抵抗，构成了一个重要的促动脉粥样硬化细胞因子。应进一步调查这些协会的机制。
There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001). Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was not significant in women (r = -0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.