上海交通大学医学院Fang Zhang 、Xun Xu和Yufan Wang小组合作的研究发现，在血糖控制良好的糖尿病患者（GW-DR）中，乙醇胺可作为糖尿病视网膜病变（DR）的生物标志物和基于生物标志物的治疗方法。相关论文于2024年1月2日发表在《科学通报》杂志上。

在这项研究中，研究人员严格遵守血糖控制指南，并在中位2年的随访期内定期进行视网膜检查，建立了一个前瞻性GW-DR队列。该队列包括从基线招募的292名糖尿病患者中挑选出的71人，他们的血红蛋白A1c（HbA1c）水平始终保持在7%以下，且未发生低血糖。在这71人的队列中，有21人随后出现了新发GW-DR，发病率为29.6%。

在验证队列中，研究人员也观察到了显著的GW-DR发生率，为17.9%。研究利用靶向代谢组学研究了GW-DR患者血清的代谢特征，发现乙醇胺水平较低与GW-DR风险之间存在显著关联。这种关联在验证队列中得到了证实，与传统的风险因子HbA1c相比，乙醇胺水平在区分GW-DR和糖尿病方面表现出更优越的诊断性能，发现队列和验证队列的AUC分别为0.954：0.506和0.906：0.521。

此外，在链脲菌素（STZ）诱导的糖尿病大鼠模型中，乙醇胺减轻了糖尿病视网膜炎症，同时抑制了小胶质细胞二酰甘油（DAG）依赖性蛋白激酶C（PKC）通路的激活。总之，研究认为乙醇胺是一种潜在的生物标志物，其表明基于生物标志物治疗GW-DR的方案具有可行性。

研究人员表示，糖尿病视网膜病变是劳动适龄人口失明的主要原因。虽然控制血糖水平能有效地将DR的发病率和发展率降低到50%以下，但目前还没有针对血糖控制良好糖尿病患者DR进展的诊断生物标志物或有效治疗方法。

附：英文原文

Title: Ethanolamine as a biomarker and biomarker-based therapy for diabetic retinopathy in glucose-well-controlled diabetic patients

Author: anonymous

Issue&Volume: 2024/01/02

Abstract: Diabetic retinopathy (DR) is the leading cause of blindness among the working-age population. Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period. The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline, all of whom consistently maintained hemoglobin A1c (HbA1c) levels below 7% without experiencing hypoglycemia. Within this cohort of 71 individuals, 21 subsequently experienced new-onset GW-DR, resulting in an incidence rate of 29.6%. In the validation cohort, we also observed a significant GW-DR incidence rate of 17.9%. Employing targeted metabolomics, we investigated the metabolic characteristics of serum in GW-DR, revealing a significant association between lower levels of ethanolamine and GW-DR risk. This association was corroborated in the validation cohort, exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c, with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts, respectively. Furthermore, in a streptozotocin (STZ)-induced diabetic rat model, ethanolamine attenuated diabetic retinal inflammation, accompanied by suppression of microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. In conclusion, we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.

DOI: 10.1016/j.scib.2023.12.053

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927323009398