胰高血糖素样肽-1受体激动剂艾塞那肽对酒精使用障碍个体促炎和代谢生物标志物的影响：一项随机、双盲、安慰剂对照临床试验的事后分析结果
Effect of the GLP-1 receptor agonist exenatide on pro-inflammatory and metabolic biomarkers in individuals with alcohol use disorder: Post hoc results from a randomized, double-blinded, placebo-controlled clinical trial.
作者信息
Hviid Malthe E B, Christoffersen Lea A N, Klausen Mette K, Brodersen Thorsten, Pedersen Ole B, Ostrowski Sisse R, Larsen Margit H, Kongstad Mette, Jensen Mathias E, Vilsbøll Tina, Fink-Jensen Anders
机构信息
Psychiatric Centre Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark.
Department of Clinical Immunology, Zealand University Hospital, Koege, Denmark.
出版信息
Alcohol Clin Exp Res (Hoboken). 2025 Aug;49(8):1659-1666. doi: 10.1111/acer.70110. Epub 2025 Jul 9.
BACKGROUND
Alcohol use disorder (AUD) has been associated with inflammation, metabolic syndrome, and increased risk of all-cause mortality. This study aimed to compare the pro-inflammatory and metabolic biomarker profiles in individuals with AUD with individuals without AUD, and to evaluate the effect of exenatide on these biomarkers in individuals with AUD.
METHODS
Serum concentrations of 25 biomarkers (interferon-γ [IFN-γ], tumor necrosis factor-α [TNF-α], interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, monocyte chemoattractant protein-1 [MCP-1], C-peptide, gastric inhibitory polypeptide [GIP], glucagon-like peptide [GLP-1], glucagon, insulin, leptin, pancreatic polypeptide [PP], adiponectin, high sensitivity C-reactive protein [hsCRP], fibroblast growth factor 21 [FGF-21], total cholesterol [CHOL], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG]) from individuals with AUD were measured at baseline and after 26 weeks of treatment with the GLP-1 receptor agonist (GLP-1RA) exenatide once-weekly or placebo, using multiplexed immunoassays, enzyme-linked immunosorbent assay (ELISA), and line immunoassays. Serum samples from 23 individuals with no record of AUD or treatment with a GLP-1RA were measured once for comparison with individuals with AUD.
RESULTS
IL-6 (1.56 vs. 0.62 pg/mL), hsCRP (3.30 vs. 1.34 mg/L), and FGF-21 (1794.97 vs. 306.11 pg/mL) were significantly higher, whereas GIP (63.06 vs. 111.07 pg/mL) was significantly lower in individuals with AUD (n = 124) than in those without AUD (n = 23). No significant changes in biomarker levels were observed after treatment with exenatide (n = 40) compared with treatment with placebo (n = 37).
CONCLUSION
Our findings support the well-established link between AUD and inflammation. However, treatment with the GLP-1 receptor agonist exenatide did not impact pro-inflammatory and metabolic biomarkers.
背景
酒精使用障碍（AUD）与炎症、代谢综合征以及全因死亡率增加有关。本研究旨在比较患有AUD的个体与未患AUD的个体的促炎和代谢生物标志物谱，并评估艾塞那肽对患有AUD的个体这些生物标志物的影响。
方法
使用多重免疫测定、酶联免疫吸附测定（ELISA）和线性免疫测定，对124例患有AUD的个体在基线时以及接受每周一次的胰高血糖素样肽-1受体激动剂（GLP-1RA）艾塞那肽或安慰剂治疗26周后，检测25种生物标志物（干扰素-γ [IFN-γ]、肿瘤坏死因子-α [TNF-α]、白细胞介素（IL）-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70、IL-13、单核细胞趋化蛋白-1 [MCP-1]、C肽、胃抑制多肽 [GIP]、胰高血糖素样肽 [GLP-1]、胰高血糖素、胰岛素、瘦素、胰多肽 [PP]、脂联素、高敏C反应蛋白 [hsCRP]、成纤维细胞生长因子21 [FGF-21]、总胆固醇 [CHOL]、高密度脂蛋白 [HDL]、低密度脂蛋白 [LDL] 和甘油三酯 [TG]）的血清浓度。对23例无AUD记录或未接受GLP-1RA治疗的个体的血清样本进行一次检测，以与患有AUD的个体进行比较。
结果
患有AUD的个体（n = 124）中，IL-6（1.56对0.62 pg/mL）、hsCRP（3.30对1.34 mg/L）和FGF-21（1794.97对306.11 pg/mL）显著更高，而GIP（63.06对111.07 pg/mL）显著更低，与未患AUD的个体（n = 23）相比。与安慰剂治疗（n = 37）相比，艾塞那肽治疗（n = 40）后生物标志物水平未观察到显著变化。
结论
我们的研究结果支持AUD与炎症之间已确立的联系。然而，胰高血糖素样肽-1受体激动剂艾塞那肽治疗并未影响促炎和代谢生物标志物。
Zotero 插件