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

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

doi:10.1016/j.scib.2023.12.053

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

Sci Bull (Beijing). 2024 Jan 2:S2095-9273(23)00939-8. doi: 10.1016/j.scib.2023.12.053. Online ahead of print.

Authors

Guangyi Hu¹, Liping Gu², Ruonan Wang¹, Qizhi Jian¹, Kangjia Lv¹, Mengxue Xia¹, Mengyu Lai², Tingting Shen², Jing Hu¹, Sen Yang³, Cunqi Ye³, Xiaonan Zhang⁴, Yufan Wang⁵, Xun Xu⁶, Fang Zhang⁷

Affiliations

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 Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: yyffwang@sina.com.
⁶ 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. Electronic address: drxuxun@sjtu.edu.cn.
⁷ 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 Treatment of Eye Diseases, Shanghai 200080, China. Electronic address: zhangfang2018@sjtu.edu.cn.

PMID: 38423871
DOI: 10.1016/j.scib.2023.12.053

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.

Keywords: Biomarker; Biomarker-based treatment; Diabetic retinopathy; Ethanolamine; Glucose-well-controlled diabetic patients; HbA1c.