Risk Of Diabetic Retinopathy Research Articles

Potential Drug Targets for Diabetic Retinopathy Identified Through Mendelian Randomization Analysis.

This study aimed to investigate the causal effect of plasma proteins on diabetic retinopathy (DR) risk and identify potential drug targets for this disease. Two-sample Mendelian randomization was performed to explore potential drug targets for DR. A total of 734 proteins were selected as instrumental variables. The Steiger filtering test and colocalization analysis were conducted to determine the causal direction and genetic pleiotropy. Plasma proteins from the decode study were used to validate the findings. Eleven plasma proteins were associated with DR risk. Genetically predicted high levels of CCL3L1 (odds ratio [OR] = 0.582; 95% confidence interval [CI], 0.343-0.986; P = 0.044), PAM (OR = 0.782; 95% CI, 0.652-0.937; P = 0.008), GP1BA (OR = 0.793; 95% CI, 0.632-0.994; P = 0.044), GALNT16 (OR = 0.832; 95% CI, 0.727-0.952; P = 0.008), POGLUT1 (OR = 0.836; 95% CI = 0.703-0.995; P = 0.043), and DKK3 (OR = 0.859; 95% CI, 0.777-0.950; P = 0.003) have the protective effect on DR risk. Genetically predicted high levels of GFRA2 (OR = 1.104; 95% CI, 1.028-1.187; P = 0.007), PATE4 (OR = 1.405; 95% CI, 1.060-1.860; P = 0.018), GSTA1 (OR = 1.464; 95% CI, 1.163-1.842; P = 0.001), SIRPG (OR = 1.600, 95% CI, 1.244-2.057; P = 2.51E-04), and MAPK13 (OR = 1.731; 95% CI, 1.233-2.431; P = 0.002) were associated with an increased risk of DR. However, the colocalization analysis results suggested that SIRPG and GP1BA have a shared causal variant with DR. CCL3L1, PAM, GALNT16, POGLUT1, DKK3, GFRA2, PATE4, GSTA1, and MAPK13 were associated with DR risk and were identified as potential drug targets for DR. The present study has highlighted the role of CCL3L1, PAM, GALNT16, POGLUT1, DKK3, GFRA2, PATE4, GSTA1, and MAPK13 in the development of DR.

NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY.

Novel therapies for diabetes have potent effects on glycemic control, obesity, and cardiovascular risk reduction, but some, including the popular drug semaglutide, have also been implicated in worsening of diabetic retinopathy (DR). Given the ubiquity of these new agents, understanding the risks to vision is important. Here, we review the data for several newly available agents in terms of systemic efficacy and retinal safety. Literature review. Novel antihyperglycemic treatments include incretin mimetics and enhancers, sodium-glucose cotransporter inhibitors, long-acting insulins, and insulin delivery systems. All improve glycemic control, and some have been shown to reduce major cardiovascular outcomes. In a pivotal trial, semaglutide was associated with approximately 75% increased risk of DR worsening. The novel long-acting insulin icodec, formulated for once weekly dosing, showed increased risk of DR worsening over a once daily insulin. No other recent antihyperglycemic agent was associated with DR worsening, although following the semaglutide trials, nearly all studies excluded patients with preexisting DR. Cases of DR worsening were rare in all instances. Dedicated safety studies for semaglutide in DR are currently underway. For most patients being considered for treatment with a novel antihyperglycemic agent, benefits on systemic metabolic and cardiovascular health are very likely to outweigh potential retinal harms. Although the true risks of the new agents on DR are unclear because their safety data come from secondary end points, the most vulnerable patients are those with preexisting high-risk DR, poor baseline glycemic control, and using insulin.

Changes in urine dipstick proteinuria and its relation to the risk of diabetic retinopathy and neuropathy.

Proteinuria is considered as a predictor for cardiovascular complications in diabetes mellitus (DM). However, no study has examined the association between changes in proteinuria and the risk of diabetic microvascular complications. Study participants were 71,825 DM patients who received urine dipstick test for proteinuria both in 2003-2004 and 2006-2007. They were categorized into four groups according to changes in proteinuria over 3 years (negative: negative → negative, resolved: proteinuria ≥ 1+ → negative, incident: negative → proteinuria ≥ 1+, persistent: proteinuria ≥ 1+ → proteinuria ≥ 1+). Cox-proportional hazard model was used in assessing the adjusted hazard ratios (HR) and 95% confidence interval (CI) for incidence of retinopathy, and neuropathy (adjusted HR [95% CI]). In all of DM patients, risk for comprehensive incidence of retinopathy and neuropathy increased in all types of proteinuria changes. In type 1 DM, HR for retinopathy and neuropathy generally increased in order of negative (reference), resolved (2.175 [1.150-4.114] and 1.335 [0.909-1.961]), incident (2.088 [1.185-3.680] and 1.753 [1.275-2.409]), and persistent proteinuria (1.314 [0.418-4.134] and 2.098 [1.274-3.455]). This pattern of relationship was similarly observed in type 2 DM for retinopathy and neuropathy: negative (reference), resolved (1.490 [1.082-2.051] and 1.164 [0.988-1.371]), incident (1.570 [1.161-2.123] and 1.291 [1.112-1.500]), and persistent proteinuria (2.309 [1.407-3.788] and 1.272 [0.945-1.712]). Risk for diabetic retinopathy and neuropathy generally increased in order of negative, resolved, incident, and persistent proteinuria. Once manifested proteinuria was associated with the increased risk of diabetic retinopathy and neuropathy even after remission of proteinuria.

Continuous Glucose Data Construction and Risk Assessment Application of Diabetic Retinopathy Complications for Patients with Type 2 Diabetes Mellitus

Managing diabetes mellitus (DM) includes achieving acceptable blood glucose levels and minimizing the risk of complications from DM. The appropriate glucose sensing method is continuous glucose monitoring (CGM). Effective evaluation metrics that reflect glucose fluctuations can be realized. However, compared with self-monitoring of blood glucose (SMBG), CGM data are not easy to obtain. Therefore, this article studies a fusion model to achieve this objective, including Gaussian process regression (GPR) and long short-term memory (LSTM). Compared with the three commonly used LSTM, GPR, and support vector machine, the proposed model can construct accurate results. By using the constructed CGM data, the conventional metrics, such as the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG), standard deviation (SD), and time in range (TIR), are calculated. These metrics and other variables are input into statistical methods to realize diabetic retinopathy risk assessment. In this way, the relationship between the glycemic variability of the constructed CGM data by the mathematical model and DR could be achieved. The utilized statistical methods include single-factor analysis and binary multivariate logistic regression analysis. Results show that fasting blood glucose, disease course, history of hypertension, MAGE and TIR are independent risk factors for DR.

To Determine the Risk-Based Screening Interval for Diabetic Retinopathy: Development and Validation of Risk Algorithm from a Retrospective Cohort Study.

The optimal screening interval for diabetic retinopathy (DR) remains controversial. This study aimed to develop a risk algorithm to predict the individual risk of referable sight-threatening diabetic retinopathy (STDR) in a mainly Chinese population and to provide evidence for risk-based screening intervals. The retrospective cohort data from 117,418 subjects who received systematic DR screening in Hong Kong between 2010 and 2016 were included to develop and validate the risk algorithm using a parametric survival model. The risk algorithm can be used to predict the individual risk of STDR within a specific time interval, or the time to reach a specific risk margin and thus to allocate a screening interval. The calibration performance was assessed by comparing the cumulative STDR events versus predicted risk over 2 years, and discrimination by using receiver operative characteristics (ROC) curve. Duration of diabetes, glycosylated hemoglobin, systolic blood pressure, presence of chronic kidney disease, diabetes medication, and age were included in the risk algorithm. The validation of prediction performance showed that there was no significant difference between predicted and observed STDR risks in males (5.6% vs. 5.1%, P=0.724) or females (4.8% vs. 4.6%, P=0.099). The area under the receiver operating characteristic curve was 0.80 (95% confidence interval [CI], 0.78 to 0.81) for males and 0.81 (95% CI, 0.79 to 0.83) for females. The risk algorithm has good prediction performance for referable STDR. Using a risk-based screening interval allows us to allocate screening visits disproportionally more to those at higher risk, while reducing the frequency of screening of lower risk people.

Protective role of SIRT1 (rs3758391 T > C) polymorphism against T2DM and its complications: Influence on GPx activity

AbstractBackground and AimsSirtuin‐1 (SIRT1) has antidiabetic effects through the regulation of insulin secretion and modulation of inflammation. The SIRT1 rs3758391 gene polymorphism affects the level of SIRT1. The current study aimed to investigate the possible influence of SIRT1 gene variants in relation to oxidative stress parameters on the susceptibility to type 2 diabetes mellitus (T2DM) and its microvascular complications.MethodsIn this case‐control study 398 individuals including 300 patients with T2DM (100 T2DM without complication, 100 diabetic neuropathy patients and 100 patients with diabetic retinopathy) and 98 healthy subjects were studied for SIRT1 rs3758391 T > C variants. Also, the glutathione peroxidase (GPx) activity and the levels of glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative status (TOS) were determined by colorimetric methods. SIRT1 genotypes were detected using the polymerase chain reaction‐restriction fragment length polymorphism method.ResultsThe C allele of SIRT1 reduced the risk of T2DM, diabetic neuropathy and diabetic retinopathy. Significantly lower levels of GSH, GPx, and TAC were found in diabetic patients compared to control group. However, the level of MDA was significantly higher in patients compared to healthy individuals. Considering all individuals, the GPx activity increased in the presence of the SIRT1 CC, and TC genotypes compared to the TT genotype. Among all studied individuals the activity of GPx was significantly higher in normal body mass index (BMI) subjects than overweight, and obese individuals. However, among overweight and obese diabetic, diabetic retinopathy and diabetic neuropathy patients the mean level of TOS was significantly higher compared to patients with normal BMI.ConclusionsOur findings suggest a protective role for SIRT1 C allele against T2DM and diabetic neuropathy and diabetic retinopathy. We found in the presence of this allele the GPx activity increased. Also, we detected an enhanced oxidative stress level among overweight and obese patients with diabetes and its complications that could be involved in the pathogenesis of the disease.

Autoimmune diseases and the risk and prognosis of latent autoimmune diabetes in adults.

The aim of this study was to clarify the impact of autoimmune disease (AD) comorbidity on the risk and prognosis of latent autoimmune diabetes in adults (LADA). We used data from a Swedish study comprising newly diagnosed cases of LADA (n=586, stratified into LADAlow and LADAhigh by autoantibody levels), type 2 diabetes (n=2003) and matched control participants (n=2355). Information on 33 ADs and diabetic retinopathy was obtained by linkage to regional and national registers. We estimated the ORs for LADA and type 2 diabetes in relation to ADs before diabetes diagnosis, and the HRs for diabetic retinopathy after diabetes diagnosis. We performed functional pathway analyses to explore biological mechanisms driving the associations. Individuals with ADs exhibit an increased susceptibility to LADA (OR 1.70; 95% CI 1.36, 2.13), particularly those with thyroid dysfunction (OR 1.88; 95% CI 1.38, 2.56), inflammatory bowel disease (OR 1.78; 95% CI 1.00, 3.16) or vitiligo (OR 3.91; 95% CI 1.93, 7.94), with stronger associations being observed for the LADAhigh phenotype. Only psoriasis was linked to type 2 diabetes (OR 1.47; 95% CI 1.08, 1.99). The biological pathways shared by LADA and ADs revolved around immune responses, including innate and adaptive immune pathways. The HRs for diabetic retinopathy in LADA patients with and without AD vs those with type 2 diabetes were 2.11 (95% CI 1.34, 3.32) and 1.68 (95% CI 1.15, 2.45), respectively. We confirm that several common ADs confer an excess risk of LADA, especially LADA with higher GADA levels, but having such a comorbidity does not appear to affect the risk of diabetic retinopathy.

Leisure screen time and diabetic retinopathy risk: A Mendelian randomization study.

The aim of this study was to investigate whether leisure screen time (LST) increases the risk of diabetic retinopathy (DR) using the Mendelian randomization (MR). This study employed a two-sample MR analysis, utilizing 63 single-nucleotide polymorphisms as instrumental variables (IVs) to assess the causal relationship between LST and the risk of Dr. To ensure the robustness of the results, a multi-effect test was conducted to evaluate the validity of the IVs. Additionally, heterogeneity tests were performed to explore differences among sub-samples. Sensitivity analyses were also conducted to further validate our findings. The impact of LST on the risk of DR was observed in both inverse variance weighted (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.04-1.43, P = 1.38 × 10-2) and weighted median (OR: 1.30, 95% CI: 1.05-1.61, P = 1.46 × 10-2) analyses. However, the MR-Egger method (OR: 0.66, 95% CI: 0.32-1.36, P = .273) did not find an increased risk of DR with increased LST. The pleiotropy test yielded a P-value of P = .09. Heterogeneity tests showed that the Q value for the inverse variance weighted method was 71.39 with a P-value of 0.17, indicating no significant heterogeneity. These results suggest that the IVs might be appropriate, and the analysis results could be robust. A large-scale MR analysis suggests a causal relationship between LST and the risk of Dr.

Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients.

Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients. The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated. The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001). Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy.

Genetically mimicked effects of thyroid dysfunction on diabetic retinopathy risk: a 2-sample univariable and multivariable Mendelian randomization study.

Thyroid dysfunction exhibits a heightened prevalence among people with diabetes compared to those without diabetes. Furthermore, TD emerges as a notable correlated risk factor for the onset of diabetic retinopathy. Using data from the FinnGen database (R9), we investigated the causal relationship between thyroid dysfunction (TD) and four stages of diabetic retinopathy (DR). A two-sample univariable Mendelian randomization (UVMR) approach was employed to estimate the total causal effect of TD on four stages of DR, while multivariable Mendelian randomization (MVMR) was used to assess the direct causal effect. The meta-analysis was conducted to summarize the collective effect of TD on four stages of DR. The inverse variance weighted (IVW) method was the primary approach for Mendelian randomization analysis, with heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analyses performed to validate the robustness of the findings. In UVMR analysis, thyrotoxicosis (TOS) was significantly associated with an increased risk of diabetic retinopathy across four stages (OR, 1.10-1.19; P<0.025). However, MVMR analysis, after adjusting for Graves' disease (GD) and/or rheumatoid arthritis (RA), revealed no significant association between TOS and the four stages of diabetic retinopathy. The Meta-analysis demonstrated the collective effect of TOS on diabetic retinopathy across all stages [OR=1.11; 95% CI (1.08-1.15); P<0.01]. In UVMR analysis, the estimates for hypothyroidism (HPT) and GD were similar to those for TOS. In the MVMR analysis, after adjusting for RA, the significant effect of HPT on DR and non-proliferative diabetic retinopathy (NPDR) remained. Additionally, MVMR analysis suggested that the estimates for GD on DR were not affected by TOS, except for GD-proliferative diabetic retinopathy (PDR). However, no significant correlation persisted after adjusting for RA, including for GD-PDR. Our study demonstrated a significant association between thyroid dysfunction TD and DR, with the relationship being particularly pronounced in HPT-DR.

Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy.

To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the "leave-one-out" sensitivity analysis demonstrated that the results were stable. Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

The relationship between weight-adjusted-waist index, body mass index and diabetic retinopathy among American adults: a population-based analysis

Diabetic retinopathy (DR) is a common complication of diabetes, with its prevalence increasing globally. While previous research has linked obesity indices such as body mass index (BMI) to DR, the association with weight-adjusted-waist index (WWI) remains unclear. Additionally, the relationship between WWI and DR has not been fully elucidated. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (2005–2008) to investigate these associations in Americans aged 40 and above. The study included 5436 participants (2705 men and 2731 women). Weighted logistic regression analysis revealed a significant increase in DR prevalence with higher WWI and BMI values. Smooth curve analysis demonstrated a linear correlation between WWI and DR. The findings suggest that both WWI and BMI are independently associated with DR risk among older US adults, highlighting the importance of considering central obesity measures in assessing diabetic complications.

The expression of long non-coding RNAs TP53TG1, LINC00342, MALAT1, H19 and MEG3 in type 2 &lt;i&gt;Diabetes mellitus&lt;/i&gt;

Type 2 diabetes is a complex and multifactorial metabolic disorder. The frequency of type 2 diabetes has dramatically increased worldwide. Long non-coding RNAs play a regulatory role in pathological processes of type 2 diabetes. The aim of the study was to analyze lncRNA TP53TG1, LINC00342, MALAT1, H19, MEG3 in patients with type 2 diabetes and metabolic parameters, as well as the risk of diabetic retinopathy. Participants included 51 patients with diabetes and 70 healthy individuals. The expression of TP53TG1 and LINC00342 genes was significantly decreased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was higher in diabetes patient. H19 gene was increased in the patients with diabetic retinopathy compare patients without retinopathy. TP53TG1, LINC00342 and MEG3 expression was decreased in the patients with diabetic retinopathy and MALAT1 expression was increased. H19 is positively correlated with triglyceride levels, TP53TG1 and LINC00342 are positively correlated with HbA1c levels and fasting glucose levels. MALAT1 is negatively correlated with HDL levels and positively correlated with LDL levels. A decrease in the expression level of TP53TG1 and LINC00342 and an increase in the level of MALAT1 in diabetes, as well as an association with glycemic control, indicate the role of the studied non-coding RNAs in the development of type 2 diabetes mellitus and retinopathy and can be considered as candidates for early diagnosis of type 2 diabetes.

Association of lipid-lowering drugs with the risk of type 2 diabetes and its complications: a mendelian randomized study

BackgroundThe pathogenesis of type 2 diabetes mellitus is somewhat associated with lipid metabolism. We aim to assess the impact of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors) on type 2 diabetes mellitus and its complications through a two-sample Mendelian randomization (MR) study.MethodWe identified suitable genetic instruments from the GWAS database that represent the expression levels of three genes, interpreting reduced genetically proxied gene expression as indicative of lipid-lowering drug use. We evaluated the causal relationships among these variables employing a two-sample Mendelian randomization approach, with the Inverse Variance Weighted (IVW) analysis serving as the primary method. Coronary artery disease was utilized as a positive control to validate the reliability of the selected genetic instruments.ResultIncreased genetically proxied HMGCR expression is significantly associated with a reduced risk of type 2 diabetes mellitus (OR = 0.64, 95%CI = 0.55–0.74), which was replicated in the FinnGen study with consistent results (OR = 0.65, 95%CI = 0.53–0.80). Increased genetically proxied HMGCR expression is associated with a reduced risk of diabetic retinopathy (OR = 0.23, 95%CI = 0.12–0.44) and diabetic nephropathy (OR = 0.35, 95%CI = 0.17–0.71). In contrast, increased genetically proxied PCSK9 expression is associated with a decreased risk of diabetic coma (OR = 0.70, 95%CI = 0.50–0.98), diabetic neuropathy (OR = 0.24, 95%CI = 0.14–0.42), diabetic retinopathy (OR = 0.67, 95%CI = 0.48–0.96), diabetic cardiovascular diseases (OR = 0.62, 95%CI = 0.38–0.99), and diabetic nephropathy (OR = 0.62, 95%CI = 0.41–0.95).ConclusionsThis Mendelian randomization study suggests an association between HMGCR and the pathogenesis of type 2 diabetes mellitus, with increased genetically proxied HMGCR expression reducing the risk of type 2 diabetes mellitus, while PCSK9 and NPC1L1 show no significant association with type 2 diabetes mellitus. These findings may offer more reasonable lipid-lowering drug options for patients with dyslipidemia.

Investigating the relationship between blood metabolites and diabetic retinopathy using two-sample mendelian randomization and in vivo validation

We addressed fundamental questions about the influence of metabolites on the development of Diabetic retinopathy (DR), and explored the related pathological mechanism. Genome-wide association study (GWAS) database data for metabolites and DR were used to perform Mendelian randomization (MR) studies. The inverse variance weighting (IVW) was chosen as the primary analysis method. Sensitivity analysis was conducted using MR-PRESSO, leave-one-out and Cochran’s Q test. Confounding factors were eliminated to ensure robustness. We also conducted metabolic pathway analysis. In vivo experimental validation was conducted using Sprague Dawley rats. The serum metabolites of the DR group rats and normal group rats were examined to evaluate the MR results. The screen identified eighteen metabolites associated with DR risk, twelve of which were known components. Seven metabolites were positively correlated with DR risk, while five could reduce it. Eight metabolites associated with proliferative DR (PDR) risk were identified, four of which are known components. Three of these were positively associated with PDR risk and one metabolite reduced PDR risk. Additionally, two possible metabolic pathways involved in the biological mechanism of DR were identified. The ELISA results showed that the serum levels of isoleucine and 4-HPA were significantly increased in DR rats, while the level of inosine was decreased. This study offers novel insights into the biological mechanisms underlying DR. Metabolites that are causally linked to DR may serve as promising biomarkers and therapeutic targets.

Association between myopia and diabetic retinopathy: A two-sample mendelian randomization study

ObjectiveThe association between myopia and diabetic retinopathy (DR) is unclear, with inconsistent results reported, and whether the association represents causality remains unknown. This study aimed to investigate the causal associations of genetically determined myopia with DR, and further explore specific mechanisms. MethodsWe conducted two-sample mendelian randomization (MR) analyses of any myopia and high myopia on six DR phenotypes, including any DR, background DR, severe background DR, proliferative DR (PDR), diabetic maculopathy and unspecific DR in the primary study. Mechanism exploration of spherical equivalent refraction (SER), corneal curvature (CC) and axial length (AL) on any DR was carried out subsequently. Single-nucleotide polymorphisms (SNPs), used as genetic instruments, were derived from UK Biobank, Genetic Epidemiology Research on Adult Health and Aging cohort and FinnGen. The inverse variance weighted (IVW) method was mainly used to assess the causality, and was complemented with sensitivity analyses and causality direction analyses. ResultsUsing SNPs that have excluded possible confounders, we discovered suggestive and positive causal associations of any myopia with any DR (IVW: odds ratio [OR] = 1.133, 95% confidence interval [95%CI]: 1.070–1.201, P = 1.91×10−5) and PDR (IVW: OR = 1.182, 95%CI: 1.088–1.285, P = 8.31×10−5). Similar but more significant associations were found of high myopia with any DR and PDR (IVW: OR = 1.107, 95%CI: 1.051–1.166, P = 1.39×10−4; OR = 1.163, 95%CI: 1.088–1.244, P = 8.76×10−6, respectively). Further mechanism analyses found only AL, rather than SER or CC, was strongly and significantly associated with any DR. These associations were robust in sensitivity analyses and causality direction analyses. ConclusionsWe found significant and positive causal associations of any myopia and high myopia with the risk of DR and PDR, which might be related with AL, indicating the significance of myopia control for preventing DR development and progression.

Initial Retinal Nerve Fiber Layer Loss and Risk of Diabetic Retinopathy Over a Four-Year Period.

The purpose of this study was to investigate whether the rapid rate of peripapillary retinal nerve fiber layer (pRNFL) thinning in short-term is associated with the future risk of developing diabetic retinopathy (DR). This prospective cohort study utilized 4-year follow-up data from the Guangzhou Diabetic Eye Study. The pRNFL thickness was measured by optical coherence tomography (OCT). DR was graded by seven-field fundus photography after dilation of the pupil. Correlations between pRNFL thinning rate and DR were analyzed using logistic regression. The additive predictive value of the prediction model was assessed using the C-index, net reclassification index (NRI), and integrated discriminant improvement index (IDI). A total of 1012 patients with diabetes (1012 eyes) without DR at both baseline and 1-year follow-up were included in this study. Over the 4-year follow-up, 132 eyes (13%) developed DR. After adjusting for confounding factors, a faster rate of initial pRNFL thinning was significantly associated with the risk of DR (odds ratio per standard deviation [SD] decrease = 1.15, 95% confidence interval [CI] = 1.08 to 1.23, P < 0.001). Incorporating either the baseline pRNFL thickness or its thinning rate into conventional prediction models significantly improved the discriminatory power. Adding the rate of pRNFL thinning further enhanced the discriminative power compared with models with only baseline pRNFL thickness (C-index increased from 0.685 to 0.731, P = 0.040). The IDI and NRI were 0.114 and 0.463, respectively (P < 0.001). The rate of initial pRNFL thinning was associated with DR occurrence and improved discriminatory power of traditional predictive models. This provides new insights into the management and screening of DR.

Hemoglobin A1c Genetics and Disparities in Risk of Diabetic Retinopathy in Individuals of Genetically Inferred African American/African British and European Ancestries.

Individuals with diabetes who carry genetic variants that lower hemoglobin A1c (HbA1c) independently of glycemia may have higher real, but undetected, hyperglycemia compared with those without these variants despite achieving similar HbA1c targets, potentially placing them at greater risk for diabetes-related complications. We sought to determine whether these genetic variants, aggregated in a polygenic score, and the large-effect African ancestry-specific missense variant in G6PD (rs1050828) that lower HbA1c were associated with higher retinopathy risk. Using data from 29,828 type 2 diabetes cases of genetically inferred African American/African British and European ancestries, we calculated ancestry-specific nonglycemic HbA1c polygenic scores (ngA1cPS) composed of 122 variants associated with HbA1c at genome-wide significance, but not with glucose. We tested the association of the ngA1cPS and the G6PD variant with retinopathy, adjusting for measured HbA1c and retinopathy risk factors. Participants in the bottom quintile of the ngA1cPS showed between 20% and 50% higher retinopathy prevalence, compared with those above this quintile, despite similar levels of measured HbA1c. The adjusted meta-analytic odds ratio for the bottom quintile was 1.31 (95% CI 1.0, 1.73; P = 0.05) in African ancestry and 1.31 (95% CI 1.15, 1.50; P = 6.5 × 10-5) in European ancestry. Among individuals of African ancestry with HbA1c below 7%, retinopathy prevalence was higher in individuals below, compared with above, the 50th percentile of the ngA1cPS regardless of sex or G6PD carrier status. Genetic effects need to be considered to personalize HbA1c targets and improve outcomes of people with diabetes from diverse ancestries.

Prevalence and Assessment of Diabetic Retinopathy in a Densely Populated Suburban Area of Tianjin, China – The Beichen Eye Study

PurposeThe aim of this study is to explore the prevalence, associated risk factors, and the influence of urbanization on the epidemiology of diabetic retinopathy (DR) and diabetic macular edema (DME). MethodsThis study utilized a cross-sectional design to survey residents aged 50 and older in the Beichen community, Tianjin. Participants underwent thorough examinations, including questionnaire surveys, laboratory blood tests, eye assessments, fundus photography, and optical coherence tomography (OCT) scans. DR was diagnosed using the retinopathy severity scale from fundus photographs based on the Early Treatment Diabetic Retinopathy Study (ETDRS) classification system. DME was identified through medical history records and OCT evaluations. In this study, we analyzed and assessed the prevalence and risk factors associated with DR and DME. ResultsThe study included 5,648 participants, and 1,182 of these were diagnosed with diabetes. Among the diabetic individuals, the prevalence of DR was 28.8%. Among the eyes of those diagnosed with DR, 37.12% had mild non-proliferative DR (NPDR), 54.81% had moderate NPDR, 6.35% (33 eyes) showed severe NPDR, and 1.73% had proliferative DR (PDR). The prevalence of DME among diabetic patients was 14.13%. Age was negatively correlated with DR (OR, 0.924), while blood glucose levels (OR, 1.123) and the duration of diabetes (OR, 1.090) were positively correlated. Additionally, blood glucose levels (OR, 1.121) and the duration of diabetes (OR, 1.070) were positively associated with DME. ConclusionIn this study, the prevalence of DR and DME was high in the Beichen District of Tianjin than in other parts of China. Maintaining effective glycemic control is the most important modifiable factor in reducing the risk of DR and DME progression and minimizing the risk of vision loss.

The influence of insulin on diabetic retinopathy and retinal vessel parameters in diabetes

AimTo investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM).MethodsA total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed.ResultsAfter adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08–2.48, P < 0.001), larger CRVE (β = 3.92, 95%CI = 2.46–5.37, P < 0.001), smaller AVR (β=-0.0083, 95%CI=-0.0121- -0.0046, P < 0.001), and larger vascular curvature (β = 0.19, 95%CI = 0.05–0.33, P = 0.008). After 3 years, insulin users had a higher risk of developing DR (OR = 1.94; 95% CI = 1.37–2.73, P = 0.002), and greater change in CRVE (β = 3.92, 95%CI = 0.96–6.88, P = 0.009).ConclusionsThe impact of insulin on the retinal microvasculature provides support for linking insulin to the increased risk of DR, as well as cardiovascular events in T2DM.