PT -期刊文章AU -最大经济产量,雅各布·t . AU -哈里Adithya AU -阿克塞尔罗德,克里斯托弗·l . AU -有限元分析Ciaran e . AU -埃里克森,梅丽莎·l . AU -科文,John p . AU - Dweik),雷德a . AU - Heresi Gustavo a TI -脂类和酮代谢的葡萄糖在肺动脉高血压控制:高血糖的夹和代谢组学研究援助- 10.1183/13993003.01700 -2019 DP - 2020年1月01 TA -欧洲呼吸杂志PG - 1901700 4099 - //www.qdcxjkg.com/content/early/2020/01/16/13993003.01700 - 2019. -短4100 - //www.qdcxjkg.com/content/early/2020/01/16/13993003.01700 - 2019. -完整的AB -背景特发性肺动脉高血压患者(PAH)显示口服葡萄糖耐量降低。这可能涉及胰腺功能或胰岛素敏感性的缺陷，但这一假说尚未得到验证;此外，在多环芳烃中对空腹营养代谢的描述仍然很少。因此，我们的目标是表征空腹营养代谢，并研究多环芳烃对高血糖的代谢反应。方法12例(6-PAH, 6-对照组)患者使用高血糖钳夹，52例(21-PAH, 31-对照组)患者进行血浆代谢组学分析。葡萄糖，胰岛素，c肽，游离脂肪酸和酰基肉碱从夹具评估。对空腹血浆标本进行血浆代谢组学研究。结果与对照组相比，clamp结果证实了多环芳烃对高血糖的胰岛素反应降低(- 53%)，但与胰腺胰岛素分泌相似。多环芳烃组骨骼肌胰岛素敏感性出乎意料的高。 Hepatic insulin extraction was elevated in PAH (+11% versus Control). Plasma metabolomics identified 862 metabolites: 213 elevated, 145 reduced in PAH (p<0.05). In both clamp and metabolomic cohorts, lipid oxidation and ketones were elevated in PAH. Insulin sensitivity, fatty acids, acylcarnitines and ketones correlated with PAH severity, while hepatic extraction and fatty acid:ketone ratio correlated with longer 6-minute walk distance.Conclusion Poor glucose control in PAH could not be explained by pancreatic ß-cell function or skeletal muscle insulin sensitivity. Instead, elevated hepatic insulin extraction emerged as an underlying factor. In agreement, nutrient metabolism in PAH favors lipid and ketone metabolism at the expense of glucose control. Future research should investigate the therapeutic potential of reinforcing lipid and ketone metabolism on clinical outcomes in PAH.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Mey reports grants from National Institutes of Health, during the conduct of the study.Conflict of interest: Dr. Hari has nothing to disclose.Conflict of interest: Dr. Axelrod has nothing to disclose.Conflict of interest: Dr. Fealy has nothing to disclose.Conflict of interest: Dr. Erickson has nothing to disclose.Conflict of interest: Dr. Kirwan reports grants from National Institutes of Health, during the conduct of the study.Conflict of interest: Dr. Dweik reports grants from National Institutes of Health, during the conduct of the study.Conflict of interest: Dr. Heresi reports grants from National Institutes of Health, during the conduct of the study.