成纤维细胞生长因子 23 与糖尿病心肌病的影像学标志物和抗糖尿病治疗药物相关。
Fibroblast growth factor-23 is associated with imaging markers of diabetic cardiomyopathy and anti-diabetic therapeutics.
机构信息
Department of Cardiology and Endocrinology, Slagelse Hospital, Ingemannsvej 32, 4200, Slagelse, Region Zealand, Denmark.
Institute of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
出版信息
Cardiovasc Diabetol. 2020 Sep 30;19(1):158. doi: 10.1186/s12933-020-01135-z.
BACKGROUND
The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes.
METHODS
In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m were excluded.
RESULTS
Median (Q1-Q3) FGF-23 was 74 (58-91) ng/L. Patients with FGF-23 above the median had lower MBF during stress (2.3 ± 0.9 vs. 2.7 ± 0.9 ml/min/g, P = 0.001) and lower overall myocardial perfusion reserve (MPR) (2.7 ± 0.8 vs. 3.3 ± 1.1, P < 0.001). LV mass (143 ± 40 vs. 138 ± 36 g, P = 0.04) and E/e* (8.5 ± 3.2 vs. 7.6 ± 2.7, P = 0.04) were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, R = 0.11) and increased E/e* (P < 0.01, R = 0.07). FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57-86) vs. 80 (60-98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues.
CONCLUSIONS
In patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23. Clinical trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331. Date of registration: February 18, 2016.
背景
生物标志物成纤维细胞生长因子 23（FGF-23）与 2 型糖尿病患者和无 2 型糖尿病患者的心血管发病率和死亡率增加有关。本研究的目的是评估 2 型糖尿病患者中 FGF-23 与心脏结构、功能和灌注之间的关系，以及评估 FGF-23 与抗糖尿病治疗以及与 2 型糖尿病相关的经典并发症和危险因素之间的关系。
方法
在这项横断面研究中，246 名 2 型糖尿病患者接受了超声心动图和高级心脏磁共振成像检查，以评估左心室（LV）结构和功能。此外，在 183 名患者中评估了静息和药物刺激（腺苷 140μg/kg/min）期间的心肌血流（MBF）。排除 eGFR<60ml/min/1.73m 的患者。
结果
中位数（Q1-Q3）FGF-23 为 74（58-91）ng/L。FGF-23 中位数以上的患者在应激时的 MBF 较低（2.3±0.9 与 2.7±0.9ml/min/g，P=0.001）和整体心肌灌注储备（MPR）较低（2.7±0.8 与 3.3±1.1，P<0.001）。FGF-23 中位数以上的患者 LV 质量（143±40 与 138±36g，P=0.04）和 E/e*（8.5±3.2 与 7.6±2.7，P=0.04）更高。在调整年龄、性别、eGFR 和高血压的线性模型中，FGF-23 升高与 MPR 降低（P<0.01，R=0.11）和 E/e*升高（P<0.01，R=0.07）相关。接受胰高血糖素样肽-1（GLP-1）类似物治疗的患者 FGF-23 水平低于未接受 GLP-1 类似物治疗的患者（71（57-86）与 80（60-98）ng/L，P=0.01）。
结论
在 2 型糖尿病且肾功能正常或轻度受损的患者中，FGF-23 水平升高与舒张功能障碍和 MPR 降低有关，这是由应激时最大 MBF 减少引起的。使用 GLP-1 类似物与 FGF-23 水平降低有关。临床试验注册 https://www.clinicaltrials.gov. 独特标识符：NCT02684331. 注册日期：2016 年 2 月 18 日。
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