Ebrahimi Fahim, Urwyler Sandrine Andrea, Betz Matthias Johannes, Christ Emanuel Remigius, Schuetz Philipp, Mueller Beat, Donath Marc Yves, Christ-Crain Mirjam
Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.
Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
Sci Rep. 2021 Apr 12;11(1):7911. doi: 10.1038/s41598-021-87207-w.
Fibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44-66), 26% were female and median BMI was 37 kg/m (IQR 34-39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by - 200 pg/mL (95%CI - 334 to - 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: - 8.8 pg/mL (95%CI - 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI - 236 to - 113; p < 0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome.Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.
成纤维细胞生长因子-21（FGF21）在代谢综合征患者中升高。尽管确切的潜在机制仍不明确，但白细胞介素-（IL）-1β表达增加所致的慢性低度炎症可能与之有关。本研究的目的是调查两种不同的抗炎治疗（IL-1拮抗或高剂量皮质类固醇）对代谢综合征患者FGF21的影响。这是对两项针对肥胖及代谢综合征特征患者的干预性研究的二次分析。试验A是一项干预性试验（n = 73），研究IL-1拮抗剂阿那白滞素和地塞米松的短期效果。试验B是一项随机、安慰剂对照、双盲试验（n = 67），研究IL-1拮抗的长期效果。两项试验共纳入140例患者。中位年龄为55岁（四分位间距44 - 66岁），26%为女性，中位体重指数为37kg/m²（四分位间距34 - 39）。几乎一半的患者患有糖尿病（45%），C反应蛋白水平升高至3.4mg/L。FGF21水平与空腹血糖水平、稳态模型评估胰岛素抵抗指数（HOMA-index）、C肽水平、糖化血红蛋白（HbA1c）和体重指数相关。阿那白滞素短期治疗使FGF21水平降低了-200pg/mL（95%置信区间-334至-66；p = 0.004）。长期治疗后未检测到效果（组间差异：-8.8pg/mL（95%置信区间-130.9至113.3；p = 0.89）。地塞米松急性治疗使FGF21降低了-175pg/mL（95%置信区间-236至-113；p < 0.001）。IL-1拮抗和皮质类固醇的抗炎治疗在短期内均可降低代谢综合征患者的FGF21水平。试验注册：ClinicalTrials.gov标识符NCT02672592和NCT00757276。
