血浆成纤维细胞生长因子 21 与肥胖和 2 型糖尿病患者非酒精性脂肪性肝炎严重程度相关。
Plasma Fibroblast Growth Factor 21 Is Associated With Severity of Nonalcoholic Steatohepatitis in Patients With Obesity and Type 2 Diabetes.
机构信息
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida College of Medicine, Gainesville, Florida.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida.
出版信息
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3327-3336. doi: 10.1210/jc.2018-02414.
CONTEXT
The relationship between plasma fibroblast growth factor 21 (FGF21), insulin resistance, and steatohepatitis has not been systematically assessed.
OBJECTIVE
To determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with nonalcoholic fatty liver disease (NAFLD).
DESIGN AND SETTING
Cross-sectional study in a university hospital.
PATIENTS INTERVENTIONS AND MAIN OUTCOME MEASURES
Patients with a body mass index >25 (n = 187) underwent: (i) euglycemic hyperinsulinemic clamp to assess tissue-specific insulin resistance (IR); (ii) liver magnetic resonance spectroscopy for intrahepatic triglyceride quantification, (iii) liver biopsy (if NAFLD present; n = 146); and (iv) fasting plasma FGF21 levels.
METHODS AND RESULTS
Patients were divided into three groups: (i) No NAFLD (n = 41); (ii) No nonalcoholic steatohepatitis (NASH) (patients with isolated steatosis or borderline NASH; n = 52); and (iii) NASH (patients with definite NASH; n = 94). Groups were well-matched for age/sex, prevalence of type 2 diabetes mellitus, and hemoglobin A1c. During euglycemic hyperinsulinemic insulin clamp, insulin sensitivity in skeletal muscle and adipose tissue worsened from No NAFLD to NASH (both P < 0.001). Plasma FGF21 levels correlated inversely with insulin sensitivity in adipose tissue (r = -0.17, P = 0.006) and skeletal muscle (r = -0.23, P = 0.007), but not with liver insulin sensitivity. Plasma FGF21 was higher in patients with NASH (453 ± 262 pg/mL) when compared with the No NASH (341 ± 198 pg/mL, P = 0.03) or No NAFLD (325 ± 289 pg/mL, P = 0.02) groups. Plasma FGF21 increased with the severity of necroinflammation (P = 0.02), and most significantly with worse fibrosis (P < 0.001), but not with worsening steatosis (P = 0.60).
CONCLUSIONS
Plasma FGF21 correlates with severity of steatohepatitis, in particular of fibrosis, in patients with NASH. Measurement of FGF21 may help identify patients at the highest risk of disease progression.
背景
血浆成纤维细胞生长因子 21（FGF21）、胰岛素抵抗和脂肪性肝炎之间的关系尚未得到系统评估。
目的
在非酒精性脂肪性肝病（NAFLD）患者中，确定较高的血浆 FGF21 是否与肝活检中更严重的脂肪性肝炎相关。
设计和设置
在一所大学医院进行的横断面研究。
患者干预和主要观察指标
体重指数>25 的患者（n=187）进行了以下检查：（i）正葡萄糖高胰岛素钳夹以评估组织特异性胰岛素抵抗（IR）；（ii）肝脏磁共振波谱分析肝内甘油三酯定量，（iii）肝活检（如果存在 NAFLD；n=146）；和（iv）空腹血浆 FGF21 水平。
方法和结果
患者被分为三组：（i）无 NAFLD（n=41）；（ii）无非酒精性脂肪性肝炎（NASH）（单纯脂肪变性或边界性 NASH 患者；n=52）；和（iii）NASH（明确的 NASH 患者；n=94）。三组在年龄/性别、2 型糖尿病患病率和血红蛋白 A1c 方面匹配良好。在正葡萄糖高胰岛素钳夹期间，骨骼肌和脂肪组织的胰岛素敏感性从无 NAFLD 到 NASH 恶化（均 P<0.001）。血浆 FGF21 水平与脂肪组织（r=-0.17，P=0.006）和骨骼肌（r=-0.23，P=0.007）的胰岛素敏感性呈负相关，但与肝脏胰岛素敏感性无关。与无 NASH 组（341±198pg/mL，P=0.03）或无 NAFLD 组（325±289pg/mL，P=0.02）相比，NASH 患者的血浆 FGF21 水平更高（453±262pg/mL，P=0.03）。血浆 FGF21 随着坏死性炎症的严重程度而增加（P=0.02），与纤维化的严重程度增加最显著（P<0.001），但与脂肪变性的恶化无关（P=0.60）。
结论
在 NASH 患者中，血浆 FGF21 与脂肪性肝炎的严重程度相关，尤其是纤维化的严重程度。测量 FGF21 可能有助于识别疾病进展风险最高的患者。
Zotero 插件