Randrianarisoa Elko, Lehn-Stefan Angela, Wang Xiaolin, Hoene Miriam, Peter Andreas, Heinzmann Silke S, Zhao Xinjie, Königsrainer Ingmar, Königsrainer Alfred, Balletshofer Bernd, Machann Jürgen, Schick Fritz, Fritsche Andreas, Häring Hans-Ulrich, Xu Guowang, Lehmann Rainer, Stefan Norbert
Department of Internal Medicine IV, University of Tübingen, Germany.
Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
Sci Rep. 2016 May 27;6:26745. doi: 10.1038/srep26745.
Circulating trimethylamine N-Oxide (TMAO) levels predict cardiovascular disease (CVD), possibly by impacting on cholesterol metabolism and oxidative stress. Because hepatic TMAO production is regulated by insulin signalling and it is unclear whether and to what extent circulating TMAO levels associate with CVD risk, independently of insulin resistance and its important determinants fatty liver and visceral obesity, we have now addressed this question in 220 subjects who participated in the Tübingen Lifestyle Intervention Program. Visceral fat mass (r = 0.40, p < 0.0001), liver fat content (r = 0.23, p = 0.0005) and TMAO levels (r = 0.26, p < 0.0001) associated positively, and insulin sensitivity associated negatively (r = -0.18, p = 0.009) with carotid intima-media thickness (cIMT). Higher TMAO levels (std.-Beta 0.11, p = 0.03) predicted increased cIMT, independently of age, sex and visceral fat mass. While during the lifestyle intervention most cardiovascular risk parameters improved, mean TMAO levels did not change (p = 0.18). However, cIMT decreased significantly (p = 0.0056) only in subjects in the tertile with the largest decrease of TMAO levels (>20%). We provide novel information that increased serum TMAO levels associate with increased cIMT, independently of established cardiovascular risk markers, including insulin resistance, visceral obesity and fatty liver. Furthermore, the decrease of cIMT during a lifestyle intervention may be related to the decrease of TMAO levels.
循环中的氧化三甲胺（TMAO）水平可预测心血管疾病（CVD），可能是通过影响胆固醇代谢和氧化应激来实现的。由于肝脏TMAO的产生受胰岛素信号调控，且目前尚不清楚循环TMAO水平与CVD风险之间是否存在关联以及关联程度如何，独立于胰岛素抵抗及其重要决定因素脂肪肝和内脏肥胖，我们现在在参与图宾根生活方式干预项目的220名受试者中解决了这个问题。内脏脂肪量（r = 0.40，p < 0.0001）、肝脏脂肪含量（r = 0.23，p = 0.0005）和TMAO水平（r = 0.26，p < 0.0001）呈正相关，而胰岛素敏感性与颈动脉内膜中层厚度（cIMT）呈负相关（r = -0.18，p = 0.009）。较高的TMAO水平（标准化β系数0.11，p = 0.03）可预测cIMT增加，独立于年龄、性别和内脏脂肪量。虽然在生活方式干预期间，大多数心血管风险参数有所改善，但平均TMAO水平没有变化（p = 0.18）。然而，仅在TMAO水平下降幅度最大（>20%）的三分位数受试者中，cIMT显著下降（p = 0.0056）。我们提供了新的信息，即血清TMAO水平升高与cIMT增加相关，独立于包括胰岛素抵抗、内脏肥胖和脂肪肝在内的既定心血管风险标志物。此外，生活方式干预期间cIMT的下降可能与TMAO水平的下降有关。
