|
2型糖尿病患者血清FNDC5水平与左室舒张功能参数的关系
|
Abstract:
目的:观察2型糖尿病(T2DM)患者血清III型纤维蛋白结构域结合蛋白5 (FNDC5)水平与正常组的差异,以及T2DM患者血清FNDC5水平与左心室舒张功能的关系,探讨其临床应用价值。方法:选取T2DM患者158例作为实验组,非2型糖尿病患者作为对照组37例。采用酶联免疫吸附试验(ELISA)检验患者血清FNDC5水平。结果:T2DM患者血清FNDC5水平较正常组血清FNDC5水平明显降低(P < 0.001)。相关系数分析显示,2型糖尿病患者中血清FNDC5浓度与E峰呈正相关(r = 0.363, P = 0.005),与E/A呈正相关(r = 0.291, P = 0.006),与E/二尖瓣瓣环间隔e’呈负相关(r = ?0.495, P = 0.000),与E/二尖瓣瓣环侧壁e’呈负相关(r = ?0.595, P = 0.000),与E/平均e’呈负相关(r = ?0.610, P = 0.000),与左房前后径呈负相关(r = ?0.304, P = 0.002)。多元有序Logistic回归分析,结果显示年龄及FNDC5水平为影响左室充盈压的独立影响因素(P < 0.05)。结论:2型糖尿病患者血清FNDC5水平显著降低,低水平FNDC5可能与2型糖尿病患者早期左室舒张功能障碍有关。
Objective: To observe the difference of the serum fibronectin type III-domain containing protein 5 (FNDC5) level between T2DM patients and normal group, and the relationship between the serum FNDC5 level and left ventricular diastolic function in T2DM patients and assess its clinical applica-tion. Method: A total of 158 T2DM patients were selected as experimental group. 37 non-T2DM pa-tients were selected as control group. Serum FNDC5 levels were detected by enzyme-linked im-munosorbent assay (ELISA). Result: The Serum FNDC5 levels in T2DM patients were significantly lower than that in control group (P < 0.001). There was a positive correlation between the serum FNDC5 level and the E peak (r = 0.363, P = 0.005) in patients with type 2 diabetes. There was a posi-tive correlation between the serum FNDC5 level and the E/A (r = 0.291, P = 0.006) in patients with type 2 diabetes. There was a negative correlation between the serum FNDC5 level and the E/mitral annulus septum e’ (r = -0.495, P = 0.000), a negative correlation between the serum FNDC5 level and the E/lateral wall of mitral annulus e’ (r = -0.595, P = 0.000), a negative correlation between the serum FNDC5 level and the E/e’ (r = -0.610, P = 0.000), and a negative correlation between the se-rum FNDC5 level and the diameter of the left atriumin (r = -0.304, P = 0.002) in the patients with type 2 diabetes. The multiple ordered Logistic regression analysis shows that age and the serum FNDC5 level are independent influencing factors for left ventricular filling pressure (P < 0.05). Con-clusions: The serum FNDC5 levels are significantly decreased in patients with type 2 diabetes mellitus, and the low levels of serum FNDC5 may be associated with early left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus.
[1] | Wang, L., et al. (2021) Prevalence and Treatment of Diabetes in China, 2013-2018. JAMA, 326, 2498-2506.
https://doi.org/10.1001/jama.2021.22208 |
[2] | Mansor, L.S., et al. (2016) Increased Oxidative Metabolism Follow-ing Hypoxia in the Type 2 Diabetic Heart, Despite Normal Hypoxia Signalling and Metabolic Adaptation. The Journal of Physiology, 594, 307-320.
https://doi.org/10.1113/JP271242 |
[3] | Hughes, W.J., et al. (2008) Role of Copper and Homocysteine in Pressure Overload Heart Failure. Cardiovascular Toxicology, 8, 137-144. https://doi.org/10.1007/s12012-008-9021-3 |
[4] | Xiong, Y., et al. (2019) Fndc5 Loss-of-Function Attenuates Exer-cise-Induced Browning of White Adipose Tissue in Mice. FASEB Journal, 33, 5876-5886. https://doi.org/10.1096/fj.201801754RR |
[5] | Sahin-Efe, A., et al. (2018) Irisin and Leptin Concentrations in Rela-tion to Obesity, and Developing Type 2 Diabetes: A Cross Sectional and a Prospective Case-Control Study Nested in the Normative Aging Study. Metabolism, 79, 24-32.
https://doi.org/10.1016/j.metabol.2017.10.011 |
[6] | El-Lebedy, D.H., Ibrahim, A.A. and Ashmawy, I.O. (2018) Novel Adipokines Vaspin and Irisin as Risk Biomarkers for Cardiovascular Diseases in Type 2 Diabetes Mellitus. Dia-betology & Metabolic Syndrome, 12, 643-648.
https://doi.org/10.1016/j.dsx.2018.04.025 |
[7] | Yin, C., et al. (2020) Irisin as a Mediator between obesity and Vas-cular Inflammation in Chinese Children and Adolescents. Nutrition, Metabolism & Cardiovascular Diseases, 30, 320-329.
https://doi.org/10.1016/j.numecd.2019.09.025 |
[8] | Dong, X., et al. (2021) Lower Serum Irisin Levels Are Associ-ated with the Increasing Mortality of Cardiovascular and Cerebrovascular Diseases in Hemodialysis Patients. Annals of Palliative Medicine, 10, 6052-6061.
https://doi.org/10.21037/apm-21-406 |
[9] | Bi, J., et al. (2020) Exercise Hormone Irisin Mitigates Endothelial Barri-er Dysfunction and Microvascular Leakage-Related Diseases. JCI Insight, 5, e136277. https://doi.org/10.1172/jci.insight.136277 |
[10] | 秦子涵, 等. FNDC5对亚临床型糖尿病心肌病的诊断价值[J]. 中华心血管病杂志, 2021(7): 687-693. |
[11] | 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版) [J]. 国际内分泌代谢杂志, 2021(5): 482-548. |
[12] | Nagueh, S.F., et al. (2016) Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Journal of the American Society of Echocardiography, 29, 277-314.
https://doi.org/10.1016/j.echo.2016.01.011 |
[13] | Nie, Y., et al. (2020) Cleavage of FNDC5 and Insights into Its Maturation Process. Molecular and Cellular Endocrinology, 510, Article ID: 110840. https://doi.org/10.1016/j.mce.2020.110840 |
[14] | Zhang, Y., et al. (2014) Irisin Stimulates Browning of White Adi-pocytes through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling. Diabetes, 63, 514-525. https://doi.org/10.2337/db13-1106 |
[15] | Yu, Q., et al. (2019) FNDC5/Irisin Inhibits Pathological Cardiac Hypertrophy. Clinical Science (London), 133, 611-627.
https://doi.org/10.1042/CS20190016 |
[16] | Rabiee, F., et al. (2020) New Insights into the Cellular Activities of Fndc5/Irisin and Its Signaling Pathways. Cell & Bioscience, 10, 51. https://doi.org/10.1186/s13578-020-00413-3 |
[17] | Tsai, Y.C., et al. (2020) Involvement of the p62/Nrf2/HO-1 Pathway in the Browning Effect of Irisin in 3T3-L1 Adipocytes. Molecular and Cellular Endocrinology, 514, Article ID: 110915. https://doi.org/10.1016/j.mce.2020.110915 |
[18] | Streese, L., et al. (2020) Physical Activity and Exercise Improve Retinal Microvascular Health as a Biomarker of Cardiovascular Risk: A Systematic Review. Atherosclerosis, 315, 33-42.
https://doi.org/10.1016/j.atherosclerosis.2020.09.017 |
[19] | Park, K.H., et al. (2013) Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome. The Journal of Clinical Endocrinology & Metabolism, 98, 4899-4907. https://doi.org/10.1210/jc.2013-2373 |
[20] | Yano, N., et al. (2020) Irisin Counteracts High Glucose and Fatty Ac-id-Induced Cytotoxicity by Preserving the AMPK-Insulin Receptor Signaling Axis in C2C12 Myoblasts. American Journal of Physiology-Endocrinology and Metabolism, 318, E791-E805. https://doi.org/10.1152/ajpendo.00219.2019 |
[21] | Song, R., et al. (2021) Irisin Improves Insulin Resistance by In-hibiting Autophagy through the PI3K/Akt Pathway in H9c2 Cells. Gene, 769, Article ID: 145209. https://doi.org/10.1016/j.gene.2020.145209 |
[22] | Liu, T.Y., et al. (2015) Irisin Inhibits Hepatic Gluconeogenesis and Increases Glycogen Synthesis via the PI3K/Akt Pathway in Type 2 Diabetic Mice and Hepatocytes. Clinical Science (London), 129, 839-850.
https://doi.org/10.1042/CS20150009 |
[23] | 路文盛, 等. PGC-1α基因MEF2C结构域482G/A变异参与2型糖尿病发病的机制研究[J]. 中华医学遗传学杂志, 2008(6): 616-623. |
[24] | DeMarco, V.G., Aroor, A.R. and Sowers, J.R. (2014) The Pathophysiology of Hypertension in Patients with Obesity. Nature Reviews Endocrinology, 10, 364-376. https://doi.org/10.1038/nrendo.2014.44 |
[25] | 潘利亚, 张晓卉, 尹新华. 糖尿病心肌病发病机制的研究进展[J]. 中国心血管杂志, 2017(2): 143-146. |
[26] | 赖纪英, 等. 慢性心力衰竭患者胰岛素抵抗与认知功能障碍相关性的研究进展[J]. 中国心血管杂志, 2015(2): 155-157. |
[27] | Jia, G., DeMarco, V.G. and Sowers, J.R. (2016) Insulin Re-sistance and Hyperinsulinaemia in Diabetic Cardiomyopathy. Nature Reviews Endocrinology, 12, 144-153. https://doi.org/10.1038/nrendo.2015.216 |
[28] | Lin, C., et al. (2021) FNDC5/Irisin Attenuates Diabetic Cardiomyo-pathy in a Type 2 Diabetes Mouse Model by Activation of Integrin αV/β5-AKT Signaling and Reduction of Oxida-tive/Nitrosative Stress. The Journal of Molecular and Cellular Cardiology, 160, 27-41. https://doi.org/10.1016/j.yjmcc.2021.06.013 |
[29] | Berezin, A.A., et al. (2022) Predictive Value of Serum Irisin for Chronic Heart Failure in Patients with Type 2 Diabetes Mellitus. Molecular Biomedicine, 3, 34. https://doi.org/10.1186/s43556-022-00096-x |