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

Guangyi Hu ¹Liping Gu ²Ruonan Wang ¹Qizhi Jian ¹Kangjia Lv ¹Mengxue Xia ¹Mengyu Lai ²Tingting Shen ²Jing Hu ¹Sen Yang ³Cunqi Ye ³Xiaonan Zhang ⁴Yufan Wang ²Xun Xu ¹Fang Zhang⁵

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作者信息

1. National Clinical Research Center for Eye Diseases,Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Eye Institute of Shanghai Jiao Tong University School,Shanghai 200080,China;Shanghai Key Laboratory of Fundus Diseases,Shanghai 200080,China;Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases,Shanghai 200080,China
2. Department of Endocrinology and Metabolism,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
3. Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology,Life Sciences Institute,Zhejiang University,Hangzhou 310058,China;Kidney Disease Center,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China
4. National Clinical Research Center for Eye Diseases,Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China
5. National Clinical Research Center for Eye Diseases,Department of Ophthalmology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Department of Endocrinology and Metabolism,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China;Eye Institute of Shanghai Jiao Tong University School,Shanghai 200080,China;Shanghai Key Laboratory of Fundus Diseases,Shanghai 200080,China;Shanghai Engineering Center for Precise Diagnosis and T
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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.

Key words

Glucose-well-controlled diabetic patients/Diabetic retinopathy/Biomarker/HbA1c/Ethanolamine/Biomarker-based treatment

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基金项目

Key R&D project of the National Ministry of Science and Technology(2023YFA1801100)

Major Research Plan of the National Natural Science Foundation of China(92357307)

Major Research Plan of the National Natural Science Foundation of China(92057106)

National Natural Science Foundation of China(32171177)

National Natural Science Foundation of China(81870610)

Shanghai Jiaotong University-Gaofeng Clinical Medicine Grant()

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

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