| BackgroundDiabetic retinopathy(DR)is the most common microvascular complication of diabetes mellitus(DM).The prevalence of DR in DM is as high as 51.3%,and it is still the main cause of blindness in people of working age.China has the largest number of DR patients in the world,and the awareness rate of DR among Chinese residents is only about 50%.Due to the low awareness of DR,weak concept of disease prevention and treatment,delay in diagnosis and treatment and miss the best treatment opportunity,serious cases lead to irreversible vision loss,seriously affect people’s quality of life,but also caused a huge burden on the social economy.Current methods of diagnosis and treatment cannot effectively avoid the progression of DR,and the prognosis of late DR is not optimistic,so early screening is of great significance in the diagnosis and treatment of DR.Biomarkers have been used to diagnose and classify a variety of diseases,including DM and DR.Melatonin(MT)is an endogenous indoleamine compound synthesized by the pineal gland and part of the retina.It has antioxidant and anti-apoptotic effects,is associated with a variety of metabolic diseases,and has a protective effect on the brain,heart,liver and other important organs.Studies have also found that MT has a potential role in the treatment of DR.At present,there are few studies on the correlation between plasma MT and DR.By detecting the plasma melatonin level of DR patients,we aim to analyze whether MT can be used as a biomarker of DR,break the traditional diagnosis and treatment method of DR,and provide a new entry point for the diagnosis and treatment of DR.ObjectiveBy studying the changes of plasma melatonin level in patients with type 2 diabetes mellitus(with or without retinopathy)and exploring the correlation between this level change and diabetes mellitus with retinopathy progression from type 2 diabetes mellitus alone,the possibility of melatonin as a marker for the early diagnosis of DR was explored,so as to provide a new idea for the diagnosis and treatment of DR.MethodsProspective case-control study.Diabetes patients were screened in the First Affiliated Hospital of Zhengzhou University from May 2020 to October 2020,and healthy people without diabetes confirmed by physical examination were included as the control group(118cases).Patients diagnosed with type 2 diabetes and treated in the ophthalmology department were the study group(182 cases).According to the 2019 Clinical Guidelines for Diabetic Retinopathy(DR PPP),DR was diagnosed and graded,and combined with the results of fundus examination,the study group was divided into 3 subgroups:the non-DR group(NDR group,57 cases),the non-proliferating DR group(NPDR group,64 cases),and the proliferating DR group(PDR group,61 cases).The plasma melatonin level was detected by ELISA kit to evaluate the relationship between plasma melatonin level and the risk and severity of DR.The changes of triglyceride(TG),total cholesterol(TC),low-density lipoprotein(LDL-C),high-density lipoprotein(HDL-C),total bilirubin(Tb),hypersensitive C-reactive protein(hs-CRP),homocysteine(Hcy),parathyroid hormone(PTH),25-hydroxyvitamin D3(25(OH)VitD3)and other indexes were compared in each group.Results1.General information:there was no statistically significant gender difference among the groups(P=0.947),the age of NPDR group and PDR group was higher than that of the control group(both P<0.001),and the differences in the course of diabetes,fasting blood glucose and hemoglobin Alc content were statistically significant(all P<0.001).Biochemical indicators:There were statistically significant differences in total bilirubin,hypersensitive C-reactive protein,blood homocysteine and 25 hydroxyvitamin D3 among all groups(P<0.05).Compared with the healthy control group and the NDR group,low bilirubin level was significantly associated with the risk of NPDR and PDR.2.The plasma melatonin levels of control group,NDR group,NPDR group and PDR group were 72.83±16.25(pg/mL),60.38±13.43(pg/mL),44.48±10.30(pg/mL)and 44.69±8.95(pg/mL),respectively,and the differences among groups were statistically significant(P<0.001).The diagnostic effect of plasma melatonin on DR was detected by ROC curve analysis.It was found that plasma melatonin could be used as a potential biomarker for the diagnosis of DR(AUC=0.893,P<0.001),and the sensitivity=0.896 and specificity=0.789 when cut off=0.685.3.Higher FBG and lower melatonin concentrations and lower 25(OH)VitD3 were associated with an increased risk of NPDR(P<0.001).In further analysis of PDR risk studies,higher levels of HbAlc and hs-CRP were found to be risk factors for PDR(P<0.001).4.There was a significant positive correlation between total bilirubin and melatonin content(P<0.001),and there was no significant correlation between PTH and MT(P=0.808).FBG and HbAlc contents,hs-CRP,and Hcy were negatively correlated with melatonin concentration(P<0.001).5.There was a significant linear correlation between total bilirubin and melatonin concentrations in subjects including control group,NDR group,NPDR group and PDR group(R2=0.438,P<0.001).Considering different DR stages,there was a significant correlation between total bilirubin and melatonin content between the NPDR and PDR groups(R2=0.360,P<0.001).Conclusions1.The plasma melatonin concentration of DR patients decreased,and the plasma melatonin can be used as a biomarker of DR,and become a sensitive and specific index for the diagnosis of DR.2.Total bilirubin and melatonin in all subjects were positively correlated;In different stages of DR,there was significant correlation between total bilirubin and melatonin contents between NPDR group and PDR group(R2=0.360,P<0.001),3.There is a negative correlation between hs-CRP and Hcy and plasma melatonin level,while 25(OH)VitD3 is positively correlated with plasma melatonin level. |
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