Hernández Cristina, Gómez-Peralta Fernando, Simó-Servat Olga, García-Ramírez Marta, Abreu Cristina, Gómez-Rodríguez Sara, Simó Rafael
Department of Endocrinology, Vall d'Hebron University Hospital, Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Diabetes Y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain.
Acta Diabetol. 2022 Nov;59(11):1437-1442. doi: 10.1007/s00592-022-01928-6. Epub 2022 Aug 4.
The response to Glucagon-like peptide-1 receptor agonists (GLP-1RAs) is highly varia-ble among patients. Thus, the identification of predictive biomarkers of therapeutic response to GLP-1 RA could help us to optimize the use of this class of drugs. GLP-1RAs increase exchange proteins directly activated by cAMP (EPAC). The aim of the present study was to assess whether the increase of EPAC1 after GLP-1RAs treatment could be a biomarker of clinical response.
After showing that GLP-1 (10 ng/mL) significantly increased the expression of EPAC1 in human endo-thelial vascular cells (HUVEC), a pilot clinical study was planned. For this purpose 49 patients with type 2 diabetes who started treatment with liraglutide were included. EPAC1 concentration was determined by ELISA before and at one month of liraglutide treatment.
We found that serum concentration of EPAC1 increased significantly after treatment with liraglutide. Only in those patients in whom EPAC1 increased (64%), a significant decrease in HbA1c, LDL-C, body mass index (BMI), and waist circumference was shown.
This pilot study suggests that the increase of circulating EPAC1 after GLP-1RAs treatment could be a useful biomarker to predict clinical GLP1-RAs response.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）在患者中的反应差异很大。因此，识别GLP-1 RA治疗反应的预测生物标志物有助于我们优化这类药物的使用。GLP-1RAs可增加直接由环磷酸腺苷（cAMP）激活的交换蛋白（EPAC）。本研究的目的是评估GLP-1RAs治疗后EPAC1的增加是否可能是临床反应的生物标志物。
在证实GLP-1（10 ng/mL）可显著增加人内皮血管细胞（HUVEC）中EPAC1的表达后，计划开展一项初步临床研究。为此，纳入了49例开始使用利拉鲁肽治疗的2型糖尿病患者。在利拉鲁肽治疗前及治疗1个月时通过酶联免疫吸附测定（ELISA）法测定EPAC1浓度。
我们发现利拉鲁肽治疗后EPAC1的血清浓度显著增加。仅在那些EPAC1增加的患者（64%）中，糖化血红蛋白（HbA1c）、低密度脂蛋白胆固醇（LDL-C）、体重指数（BMI）和腰围显著降低。
这项初步研究表明，GLP-1RAs治疗后循环中EPAC1的增加可能是预测GLP-1RAs临床反应的有用生物标志物。
