Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study
Synergistic association of elevated serum free fatty acid and glucose levels with large arterial stiffness in a general population: The Nagahama Study
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一般人群中血清游离脂肪酸和葡萄糖水平升高与大动脉僵硬度的协同关联：Nagahama 研究
DOI：
10.1016/j.metabol.2015.10.011
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
on behalf of the Nagahama Study group.
中科院分区：
文献类型：
--
作者：
Yasuharu Tabara;Yoshimitsu Takahashi;Kazuya Setoh;Takahisa Kawaguchi;Norimoto Gotoh;Chikashi Terao;Ryo Yamada;Shinji Kosugi;Akihiro Sekine;Takeo Nakayama;Fumihiko Matsuda;on behalf of the Nagahama Study group.
背景先前的研究报道，人为增加循环中游离脂肪酸(FFA)水平可能会对血管系统产生不利影响。然而，这种影响是否可以外推到FFA水平的生理变化还没有弄清楚。鉴于游离脂肪酸对胰腺β细胞具有脂毒作用，并可能直接损伤动脉内皮细胞，我们推测这些不良反应可能与高血糖有协同作用。在基线检查时测量血清FFA水平。结果由于血清游离脂肪酸水平在胰岛素水平较高的受试者中显著降低，只有在禁食(≥为12小时，P=0.001)或接近禁食(5-11小时，P<；0.001)条件下采血的受试者，血清游离脂肪酸水平与动脉硬化程度显著相关，而在非禁食条件下采血的受试者则无相关性。虽然2型糖尿病和糖化血红蛋白显示与BaPWV有很强的相关性，但在调整血糖水平后，FFA水平和BaPWV之间的关联仍然显著(β=0.052，P<；0.001)。除了它们的直接关系外，游离脂肪酸和血糖水平还与BaPWV有协同作用(FFA⁎葡萄糖；β=0.036，P<；0.001)。根据FFA和血糖的组合，最低和最高亚组之间的baPWV差异约为300 cm/s。结论FFA浓度的生理性变化可能是大动脉僵硬的危险因素。FFA和高血糖对血管系统有协同的不良影响。
BackgroundPrevious studies have reported that artificial increases in circulating free fatty acid (FFA) levels might have adverse effects on the vasculature. However, whether or not this effect can be extrapolated to physiological variations in FFA levels has not been clarified. Given that FFAs exert a lipotoxic effect on pancreatic β-cells and might directly damage the arterial endothelium, we hypothesized that these adverse effects might synergize with hyperglycemia.MethodsA total of 9396 Japanese subjects were included in the study. Serum FFA levels were measured at baseline examination. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness.ResultsAs serum levels of FFA were markedly lower in subjects with higher insulin level, a significant association between FFA levels and baPWV was observed only in subjects with blood samples taken under fasting (≥ 12 h,P< 0.001) or near-fasting (5–11 h,P< 0.001) conditions, and not in those taken under non-fasting (< 5 h,P= 0.307) conditions. Although type 2 diabetes and HbA1c showed a strong association with baPWV, the association between FFA level and baPWV remained significant (β = 0.052,P< 0.001) after adjustment for glycemic levels. In addition to their direct relationship, FFA and glucose levels were synergistically associated with baPWV (FFA⁎glucose; β = 0.036,P< 0.001). Differences in baPWV between the lowest and highest subgroups divided by a combination of FFA and glucose reached approximately 300 cm/s.ConclusionsPhysiological variations in FFA concentrations might be a risk factor for large arterial stiffness. FFA and hyperglycemia exert a synergistic adverse effect on the vasculature.