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

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.
Guangyi Hu 1,  Liping Gu 2,  Ruonan Wang 1,  Qizhi Jian 1,  Kangjia Lv 1,  Mengxue Xia 1,  Mengyu Lai 2,  Tingting Shen 2,  Jing Hu 1,  Sen Yang 3,  Cunqi Ye 3,  Xiaonan Zhang 4,  Yufan Wang 5,  Xun Xu 6,  Fang Zhang 7
Affiliations

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.

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