Association of erythropoietin gene polymorphism (rs1617640 C>T/G) with diabetic retinopathy in Type 2 diabetes mellitus patients of Punjabi population in Pakistan

Objective To establish an appropriate diabetic retinopathy (DR) risk assessment model for patients with type 2 diabetes mellitus (T2DM). Methods A retrospective clinical analysis. From January 2016 to December 2017, 753 T2DM patients in the Third Affiliated Hospital of Southern Medical University were analyzed retrospectively. Digital fundus photography was taken in all patients. Fasting plasma glucose (FPG), HbA1c, total bilirubin (TB), blood platelet, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), apolipoprotein-A (apoA), apolipoprotein-B (apoB), serum creatinine, blood urea nitrogen (BUN), blood uric acid, fibrinogen (Fg), estimated glomerular filtration (eGFR) were collected. The patients were randomly assigned to model group and testify group, each had 702 patients and 51 patients respectively. Logistic regression was used to screen risk factors of DR and develop an assessment scale that can be used to predict DR. Goodness of fit was examined using the Hosmer- Lemeshow test and the area under the receiver operating characteristic (ROC) curve. Results Among 702 patients in the model group, 483 patients were DR, 219 patients were NDR. The scores for DR risk were duration of diabetes ≥4.5 years, 4 points; total bilirubin <6.65 mol/L, 2 points; apoA≥1.18 g/L, 2 points; blood urea≥ 6.46 mmol/L, 1 points; HbA1c ≥7.75%, 2 points; HDL-c <1.38 mmol/L, 2 points; diabetic nephropathy, 3 points; fibrinogen, 1 point. The area under the receiver operating characteristic curve was 0.787. The logistic regression analysis showed that the risk factors independently associated with DR were duration of diabetes (β=1.272, OR=3.569, 95%CI 2.283−5.578, P<0.001), TB (β=0.744, OR=2.104, 95%CI 1.404−3.152, P<0.001, BUN (β=0.401, OR=1.494, 95%CI 0.996−2.240, P=0.052), HbA1c (β=0.545, OR=1.724, 95%CI 1.165−2.55, P=0.006), HDL-c (β=0.666, OR=1.986, 95%CI 1.149−3.298, P=0.013), diabetic nephropathy (β=1.151, OR=3.162, 95%CI 2.080−4.806, P=0.013), Fg (β=0.333, OR=1.396, 95%CI 0.945−2.061, P=0.094). The risk model was P=1/[1+exp−(−3.799+1.272X1+0.744X2+0.769X3+0.401X4+0.545X5+0.666X6+1.151X7+0.333X8)]. X1= duration of diabetes, X2=TB, X3=apoA, X4=BUN, X5=HbA1c, X6=HDL-c, X7=diabetic nephropathy, X8=Fg. The area under the ROC curve was 0.787 and the Hosmer-Lemeshow test suggested excellent agreement (χ2=10.125, df=8, P=0.256) in model group. The area under the ROC curve was 0.869 and the Hosmer-Lemeshow test suggested excellent agreement (χ2=5.345, df=7, P=0.618) in model group. Conclusion The area under the ROC curve for DR was 0.787. The duration of diabetes, TB, BUN, HbA1c, HDL-c, diabetic nephropathy, apoA, Fg are the risk factors of DR in T2DM patients. Key words: Diabetic retinopathy/prevention & control; Models, statistical; Forecasting

ObjectiveTo investigate the association of the rs741301 polymorphism in theELMO1 gene with diabetic retinopathy (DR) in patients with type 2diabetes mellitus (T2DM).Materials and methodsThis study analyzed 350 patients withT2DM and DR (cases) and 234 patients withT2DMwithout this complication but with more than 10 years of diabetes mellitus (DM)(controls). DR was diagnosed by indirect fundoscopy. Genotyping was performed by allelicdiscrimination real-time PCR.ResultsThe frequency of the C/C genotype of the rs741301 polymorphism in theELMO1 gene was 26.9% in cases and 17.9% in controls (P = 0.011).After adjustment for covariables, the C/C genotype was associated with an increased riskof DR [odds ratio (OR) = 1.805, 95%CI 1.101–2.961; P = 0.019]. This association remainedsignificant in dominant and additive inheritance models after adjustment for the samevariables [OR = 1.597, 95%CI 1.089-2.343; P = 0.017; and OR = 1.818, 95%CI 1.099-3.007;P = 0.020].ConclusionThis study demonstrated an association between the presence of the C allele of theELMO1 rs741301 polymorphism and an increased risk of DR in patientswith T2DM from Southern Brazil.

Psoriasis and risk of diabetic retinopathy in patients with type 2 diabetes mellitus.

Introduction: Angiopoietin-2 (ANGPT-2) is a member of a growth factor family that binds to the endothelial receptor tyrosine kinase 2 and regulates vascular development and function. Under hyperglycemic conditions, ANGPT-2 is upregulated and leads to vascular destabilization, pericyte dropout, and aggravation of inflammation. In this context, studies have reported the involvement of ANGPT-2 in the pathogenesis of diabetic retinopathy (DR). Thus, polymorphisms in ANGPT-2 gene may be of interest in this field. Objective: To investigate the association between the rs2442598 polymorphism in the ANGPT-2 gene and DR. Methods: This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Results: Genotype distributions of this polymorphism were consistent with Hardy-Weinberg Equilibrium. Frequency of the rs2442598 A allele was higher in cases compared to controls (P= 0.011). Moreover, the A/A genotype was higher in cases than controls (P= 0.017) and was associated with risk for DR after adjustment for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and presence of hypertension (OR= 5.19, IC95% 1.21 - 22.27). This association was maintained under the recessive (OR= 4.78, IC95% 1.14 - 19.99) and additive (OR= 6.861, IC95% 1.45 - 32.38) inheritance models. Conclusion: Our data demonstrate, for the first time, the association of the ANGPT-2 rs2442598 A allele with risk for DR in T1DM patients from Southern Brazil.

As studies have reported the involvement of angiopoietin-2 (ANGPT-2) in the pathogenesis of diabetic retinopathy (DR), the aim of this study was to investigate the association between the ANGPT-2 rs2442598 polymorphism and DR. This case-control study comprised 107 patients with type 1 diabetes mellitus (T1DM) and DR (cases) and 129 patients with T1DM without DR (controls) and with ≥ 10 years of DM. The ANGPT-2 rs2442598 (G/A) polymorphism was genotyped by real-time PCR using TaqMan MGB probes. Genotype distributions of this polymorphism were consistent with the Hardy-Weinberg equilibrium. The frequency of the rs2442598 A allele was higher in cases compared to controls (p = 0.011). Moreover, the A/A genotype was more frequent in cases than in controls (p = 0.017) and was associated with risk for DR after adjustments for duration of DM, HbA1c, triglycerides, estimated glomerular filtration rate, and hypertension (odds ratio [OR] = 5.19, 95% confidence interval [CI] 1.21-22.27). This association was maintained under recessive (OR = 4.78, 95% CI 1.14-19.99) and additive (OR = 6.861, 95% CI 1.45-32.38) inheritance models. Our data demonstrated, for the first time, an association between the ANGPT-2 rs2442598 A allele and risk for DR in T1DM patients from southern Brazil. Additional studies are necessary to replicate this association in other populations.

Opioid use disorder (OUD), cannabis use disorder (CUD) and cocaine use disorder have been associated with a range of adverse health outcomes, including certain ocular manifestations; however, their impact on diabetic retinopathy (DR) remains insufficiently explored. This study aimed to measure the association between OUD, CUD and cocaine use disorder and the risk of DR among patients with type 2 diabetes mellitus (T2DM). Propensity-score-matched retrospective cohort study. This study used the TriNetX US Collaborative Network to access electronic health records (EHRs), including data on demographics, diagnoses, medication use and laboratory results. A total of 131 088 adult patients with T2DM and comorbid OUD, CUD or cocaine use disorder, and 131 088 adult patients with T2DM without these conditions, were identified following propensity score matching. The primary outcome was the risk of DR evaluated over a 5-year follow-up period. The risks of various DR subtypes and diabetic macular edema (DME) were also assessed. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Over a 5-year follow-up period, patients with T2DM comorbid with OUD, CUD or cocaine use disorder had a statistically significantly higher risk of developing DR [HR (95% CI) =2.90 (2.55-3.30), P < 0.00] compared with those without any drug use disorder. Drug use disorders were also associated with elevated risks of vision-threatening diabetic retinopathy (VTDR) [HR (95% CI) =2.78 (2.24-3.46), P < 0.00], non-proliferative diabetic retinopathy (NPDR) [HR (95% CI) =3.10 (2.61-3.68), P < 0.00], proliferative diabetic retinopathy (PDR) [HR (95% CI) =3.17 (2.26-4.45), P < 0.00] and DME [HR (95% CI) =2.64 (2.04-3.42), P < 0.00] among patients with T2DM. Opioid use disorder, cannabis use disorder and cocaine use disorder appear to be associated with an elevated risk of diabetic retinopathy among patients with type 2 diabetes mellitus.

ObjectiveTo investigate the relationship between the atherogenic index of plasma (AIP) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 584 patients with T2DM were divided into two groups based on whether with DR (non-DR group, n = 382; DR group, n = 202). The association between AIP and DR was assessed by Spearman’s correlation and bivariate/multivariate logistic regression.ResultsThe patients in the DR group showed significantly higher AIP levels than those in the non-DR group (−0.009 ± 0.226 vs. 0.186 ± 0.261, p < 0.001). Compared with those without DR, DR group had higher levels of age, systolic blood pressure (SBP), body mass index (BMI), diabetes duration, triglycerides (TG), blood urea nitrogen (BUN) and creatinine (Cr), while direct bilirubin (DBIL) and high-density lipoprotein cholesterol (HDL-C) were lower (p < 0.05). According to the interquartile range of AIP, the participants were divided into four groups: Q1 (≤−0.130), Q2 (−0.129, 0.048), Q3 (0.049, 0.220), Q4 (≥0.221). After adjusting for age, BMI, SBP, diabetes duration, DBIL, BUN and Cr, the logistic regression model indicated that subjects in Q3 and Q4 still had a remarkably increased risk of DR (Q3: OR, 2.838, 95% CI: 1.268 ~ 7.067; Q4: OR, 4.414, 95% CI: 1.841 ~ 10.097; all p < 0.05). AIP provided an AUC value of 0.697 for retinopathy in patients with T2DM (95% CI: 0.652 ~ 0.741).ConclusionAIP is associated with diabetic retinopathy in patients with T2DM, and AIP may be a potential predictor of DR in patients with T2DM.

To investigate the relationship between serum C1q tumor necrosis factor-related protein 9 (CTRP9) level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 291 patients with T2DM underwent fundus examination, and their serum levels of CTRP9, insulin and adiponectin were measured using enzyme- linked immunosorbent assay. According to results of fundus examination, the patients were divided into DR group and non-DR (NDR) group, and logistic regression was used to analyze the relationship between serum CTRP9 levels and DR in T2DM patients. Compared with those in NDR group, the patients with DR showed significantly increased serum CTRP9 level (P < 0.001) and decreased serum adiponectin level (P < 0.001). Pearson correlation analysis showed that in patients with T2DM complicated by DR, serum CTRP9 levels had a significant positive correlation with DR stage (P < 0.05) and a negative correlation with serum adiponectin level (P < 0.001). Multivariate logistic regression analysis showed that with the increase of serum CTRP9 level, the risk of DR is significantly increased in patients with T2DM. In patients with T2DM complicated by DR, an increased serum CTRP9 level suggests a compensatory response to DR.

Objective To investigate the correlation between serum bilirubin level and the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus of different sexes. Methods A total of 1 304 patients with type 2 diabetes mellitus were included in this study. The clinical data were collected and fundus examination was performed. According to the results of fundus examination, the patients were divided into DR group and Non-DR (NDR) group. The correlation between the levels of serum total bilirubin, direct bilirubin, indirect bilirubin, and the occurrence of DR was analyzed. Results The levels of total bilirubin, direct bilirubin, and indirect bilirubin in DR group were significantly lower than those in NDR group. Univariate analysis showed that the levels of total bilirubin and indirect bilirubin were negatively correlated with the occurrence of DR (P<0.01). There was no significant correlation between the level of direct bilirubin and the occurrence of DR. Smooth curve fitting showed that there was a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in women, while a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in men. The results of multiple regression analysis showed that in men total bilirubin increased by 1 μmol/L, the risk of DR decreased by 8% (OR=0.92, 95%CI 0.88-0.98, P<0.01). Indirect bilirubin increased by 1 μmol/L, and the risk of DR decreased by 9% (OR=0.91, 95%CI 0.84-0.96, P<0.01). In women, when total bilirubin<12.8 μmol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR decreased by 17%(OR=0.83, 95%CI 0.72-0.95, P<0.01); When total bilirubin≥12.8 umol/L, for every 1 μmol/L increase in total bilirubin, the risk of DR increased by 10%(OR=1.10, 95%CI 1.01-1.20, P<0.05); When indirect bilirubin<9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR decreased by 20%(OR=0.80, 95%CI 0.68-0.94, P<0.01); When indirect bilirubin≥9.8 μmol/L, for every 1 μmol/L increase in indirect bilirubin, the risk of DR increased by 13%(OR=1.13, 95%CI 1.01-1.25, P<0.05). Conclusion This study shows that there is a U-shaped relationship between the levels of total bilirubin and indirect bilirubin and the risk of DR in female patients with type 2 diabetes mellitus, and there is a negative correlation between total bilirubin, indirect bilirubin and the risk of DR in male patients. However, there was no significant correlation between direct bilirubin and DR risk. Key words: Diabetes mellitus, type 2; Diabetic retinopathy; Bilirubin

ObjectiveThis study sought to explore the association of magnesium (Mg) status and blood glucose control, represented by Mg depletion score (MDS) and hemoglobin A1c (HbA1c) level, respectively, with the risk of diabetic retinopathy (DR) among type 2 diabetes mellitus (T2DM) patients, and whether there were interactions between Mg status and blood glucose control on the risk of DR.MethodsData of this cross-sectional study were extracted from the National Health and Nutrition Examination Surveys (NHANES) database 2005–2018. MDS was an indicator to assess the overall Mg status in the human body that considers the pathophysiological factors influencing the kidneys’ reabsorption capability. Blood glucose control was represented by hemoglobin A1c (HbA1c) and HbA1c level ≥7% referred to poor blood glucose control. Receiver Operating curve (ROC) analysis was performed to evaluate the predictive performance of MDS and HbA1c for DR. Weighted univariate and multivariate analyses were utilized to explore the MDS and HbA1c and their interactions effects on the risk of DR, with odds ratios (ORs), 95% confidence intervals (CIs), relative excess risk due to interactions (RERI) and attributable proportion due to interactions (AP). These interactions were further explored based on the age, gender, and cardiovascular disease (CVD) history.ResultsA total of 4487 T2DM patients were included, of whom 942 (20.99%) had DR. After covariate adjustment, both high MDS (≥2) and elevated HbA1c levels (≥7%) demonstrated significant independent associations with increased DR risk. ROC analysis showed MDS (AUC = 0.766) and HbA1c (AUC = 0.749) in fully adjusted models. Significant interactions between MDS and HbA1c amplified DR risk beyond individual effects, with this pattern most pronounced among female patients, those aged ≥60 years, and individuals with a cardiovascular disease history.ConclusionsThe results of this study suggested that high MDS as well as high HbA1c level may have interaction effects on the high risk of DR among T2DM patients.

Screening for Diabetic Retinopathy in Youth-Onset Diabetes

Background Diabetic retinopathy (DR) is one oi primary causes of blindness in young adutts with the increase of incidence of diabetes mellitus (DM).To strengthen the anlysis of risk factors for incidence and progression of retinopathy is very important for the prevention and control of DR in China.Objective The aim of this study was to describe the risk factors associated with DR in type 2 DM patients aged 40 ycars and older in Hengli town,Dongguan city in Southern China.Methods A population-based cross-sectional study was performed.A total of 8952 Han Chinese from 16 villages and a community participated in the census of DM based on the diagnosis criteria of American Diabetic Association (2010 Version),and then the DR was screened and staged from the DM patients according to International Clinical Classification System of DR and DME (Sydney,2002).Participants underwent standardized interview,physical,laboratory and ocular examination.Ocular examination included visual acuity(best corrected visual acuity and presenting visual acuity),intraocular pressure,anterior and posterior segment examinations,fundus and optic disc photography.x2 test,independent sample t test and one way analysis of virance was respectively used to compare the differences of examing indexes between DR and non-DR (NDR).Univariate and stepwise logistic regression analysis were used to identify independent risk factors.Results Stepwise logistic regression analysis revealed that male,longer DM course,systolic pressure,hyperglycemia and glycosylated hemoglobin were the independent risk factors of DR.Compared with females,males had a higher risk of DR (OR =1.914) (95％CI:1.382-2.651).The risk of DR was significantly increased in the DM patients with the duration of 1-4 years,5-9 years and ≥ 10 years in comparison with newly diagnosed DM patients (OR =3.336,95％ CI:2.322-4.880 ; OR =3.890,95％ CI:2.327-6.503 ; OR =12.499,95％ CI:6.607-23.647).DM patients with blood pressure 120-139 mmHg and ≥ 140 mmHg showed a higher risk of having any DR than those with blood pressure ≤ 120 mmHg (OR =1.953,95％ CI:1.081-3.528 ; OR =1.950,95％ CI:1.076-3.532).Compared with DM patients with fasting blood glucose ≤5.6 mmol/L,DM patients with 5.6-6.9 mmol/L and≥7.0 mmol/L had a higher risk of having any DR (OR=1.567,95％ CI:0.889-2.732) and OR =2.170,95％ CI:1.252-3.761).Compared with DM patients with glycosylated hemoglobin＜6.5％,DM patients with ≥ 6.5％ had a higher risk of having any DR (OR =1.577,95％ CI:1.105-2.253).Conclusions This study indicates that male,duration of diabetes,systolic pressure,hyperglycemia and glycosylated hemoglobin are independent risk factors of DR in type 2 DM patients.These findings suggest that controlling hyperglycemia,hypertension and body weight index may lower the risk of having DR associated with type 2 DM. Key words: Diabetes mellitus/complication; Diabetic retinopathy; Risk factor; Epidemiology

To investigate the association of diabetic self-management with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. Cross-sectional study. Recruited patients with type 2 diabetes mellitus in the Desheng community of urban Beijing between November 2009 and May 2011. All patients were surveyed using a standardized questionnaire and underwent detailed ophthalmic examination. Patients were classified into DR group or diabetic without retinopathy (DWR) group according to the grading of fundus color photographs using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard grading protocol. In the DR group, proliferative diabetic retinopathy (PDR) was further defined. The overall levels of diabetes self-management in the study population were assessed and compared for the differences between DR and DWR, PDR and NPDR groups. One thousand one hundred patients with type 2 diabetes mellitus were recruited. The prevalence of DR was 32.1% (353/1100) in the study population. Sixty-three percent (652/1035) of patients had glycated hemoglobin (HbA1c) level less than 7.0%. The majority of patients (85.4%, 916/1072) conducted a diet control, 77.3% (827/1070) exercised, 56.0% (609/1088) monitored blood glucose regularly, 56.8% (416/733) detected HbA1c more than once every six months, 71.7% (762/1062) had ophthalmologic examination after the diagnosis of diabetes mellitus, and 47.9% (525/1097) had mydriatic check-up. Increased risk of DR was associated with longer duration of diabetes (more than 10 years) (OR = 3.90, 95% CI:2.97-5.51, P < 0.05), higher HbA1c level of ≥ 7.0% (OR = 3.23, 95% CI:2.44-4.28, P < 0.05), insulin therapy (OR = 4.82, 95% CI:3.55-6.57, P < 0.05), male gender (OR = 1.41, 95% CI:1.08-1.84, P < 0.05), lower level of education (OR = 1.90, 95% CI:1.39-2.62, P < 0.05), lower monthly income (OR = 1.46, 95% CI:1.12-1.91, P < 0.05), lower obedience to diet control (OR = 1.72, 95% CI:1.22-2.43, P < 0.05), no exercise (OR = 1.42, 95% CI:1.04-1.94, P < 0.05), change of therapeutic protocol during the last five years (OR = 1.78, 95% CI:1.32-2.41, P < 0.05), and family history of diabetes (OR = 1.35, 95% CI:1.01-1.78, P < 0.05). Increased risk of PDR was associated with the diagnosis age of diabetes (OR = 0.92, 95% CI:0.89-0.95, P < 0.05), longer duration of diabetes (more than 10 years) (OR = 4.54, 95% CI:1.95-12.32, P < 0.05), and insulin therapy (OR = 4.85, 95% CI:2.34-10.90, P < 0.05). In the multifactor logistic regression model, male gender (OR = 2.21, 95% CI:1.57-3.11, P < 0.05), lower level of education (OR = 1.98, 95% CI:1.33-2.94, P < 0.05), lower monthly income (OR = 1.66, 95% CI:1.15-2.39, P < 0.05) ,longer duration of diabetes (more than 10 years) (OR = 2.46, 95% CI:1.77-3.41, P < 0.05) ,HbA1c ≥ 7.0% (OR = 2.24, 95% CI:1.64-3.07, P < 0.05) and insulin therapy (OR = 3.38, 95% CI:2.38-4.8, P < 0.05) were associated with higher risk of DR. The diagnosis age of diabetes (OR = 0.94, 95% CI:0.91-0.98, P < 0.05) and insulin therapy (OR = 3.49, 95% CI:1.47-8.27, P < 0.05) were associated with PDR. Higher risk of DR is associated with longer duration of diabetes,insulin therapy, higher HbA1c level, male gender, and lower level of education, whereas higher risk of DR is also associated with lower obedience to diet control and less exercise, which suggest that lower level of diabetic self-management increased the risk of DR.

Purpose To assess the relationship between metformin use and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of metformin dosage on reducing the incidence of DR. Methods The study population included patients with newly diagnosed T2DM, who were aged ≥20 years and prescribed with antidiabetic drug therapy lasting ≥90 days, as identified using the National Health Insurance Research Database between 2000 and 2012. We matched metformin users and nonusers by a propensity score. Cox proportional hazard regression analyses were used to compute and compare the risk of developing nonproliferative diabetic retinopathy (NPDR) in metformin users and nonusers. Results Overall, 10,044 T2DM patients were enrolled. Metformin treatment was associated with a lower risk of NPDR (aHR 0.76, 95% CI 0.68–0.87) and sight-threatening diabetic retinopathy (STDR, aHR 0.29, 95% CI 0.19–0.45); however, the reduction in risk was borderline significant for STDR progression among NPDR patients (aHR 0.54, 95% CI 0.28–1.01). Combination therapy of metformin and DPP-4i exhibited a stronger but inverse relationship with NPDR development (aHR 0.32, 95% CI 0.25–0.41), especially at early (<3 months) stages of metformin prescription. These inverse relationships were also evident at different metformin doses and in adapted Diabetes Complications Severity Index scores (aDCSI). Moreover, combination therapy of metformin with sulfonylureas was associated with an increased risk of NPDR. Conclusion Metformin treatment in patients with T2DM was associated with a reduced risk of NPDR, and a potential trend was found for a reduced STDR risk in patients who had previously been diagnosed with NPDR. Combining metformin with DPP-4i seemingly had a significantly beneficial effect against NPDR risk, particularly when aDCSI scores were low, and when metformin was prescribed early after T2DM diagnosis. These results may recommend metformin for early treatment of T2DM.

Objective To conduct a systematic review and updated meta-analysis on the potential association between endothelial nitric oxide synthase (eNOS) 4a/b polymorphism and the risk of developing diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to identify possible clinical biomarkers for early screening of DR. Materials and methods A meta-analysis based on case-control or cross-sectional studies was conducted to examine the correlation between eNOS 4a/b polymorphism and DR. Pooled odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association strength. Results We included 19 studies, covering 7838 subjects. An association was observed in Caucasians (allelic model: OR = 1.273, 95% CI: 1.006–1.610, p = .045; recessive model: OR = 0.575, 95% CI: 0.371–0.892, p = .014; dominant model: OR = 1.268, 95% CI: 1.052–1.528, p = .013; homozygote model: OR = 1.833, 95% CI: 1.176–2.856, p = .007). Moreover, population-based studies have indicated an association between eNOS 4a/b polymorphism and DR susceptibility. Conclusions The present study showed that intron 4a allele of eNOS 4a/b is a risk factor for DR in Caucasians with T2DM. Thus, eNOS 4a/b may be used as a biomarker for the early screening and diagnosis of DR in Caucasian T2DM patients.