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 c...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-wellcontrolled 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.展开更多
基金supported by the Key R&D project of the National Ministry of Science and Technology(2023YFA1801100)the Major Research Plan of the National Natural Science Foundation of China(92357307 and 92057106)+1 种基金the National Natural Science Foundation of China(32171177 and 81870610)Shanghai Jiaotong University-Gaofeng Clinical Medicine Grant。
文摘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-wellcontrolled 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.
