AST/ALT ratio is an independent risk factor for diabetic retinopathy: A cross-sectional study.
Medicine
The aspartate to alanine transaminase (AST/ALT) ratio indicates oxidative stress and inflammatory reactions related to the occurrence of diabetic retinopathy (DR). Currently, there are no reports on the correlation between AST/ALT ratio and DR. Hence, this study aimed to explore the relationship between AST/ALT ratio and DR. This cross-sectional study utilized data from the Metabolic Management Center of the First People's Hospital in City. In total, 1365 patients with type 2 diabetes mellitus (T2DM) participated in the study, including 244 patients with DR and 1121 patients without DR. We collected the results of fundus photography, liver function, and other research data and grouped them according to tertiles of AST/ALT ratios. DR prevalence was the highest in the group with the highest AST/ALT ratio (22.12%, P = .004). Both univariate (OR = 2.25, 95% CI: 1.51-3.34, P < .001) and multivariable logistic regression analyses (adjusted for confounding factors) showed that the risk of DR increased by 36% when the AST/ALT ratio increased by 1 standard deviation (SD) (OR = 1.36, 95% CI: 1.16-1.59, P < .001), and 29.3% was mediated by the duration of diabetes. A sensitivity analysis confirmed the stability of the results. This study showed that an increase in AST/ALT ratio is an independent risk factor for DR.
10.1097/MD.0000000000038583
The non-linear relationship between serum albumin and diabetic retinopathy in type 2 diabetes mellitus: a secondary analysis based on a cross-sectional study.
BMC ophthalmology
BACKGROUND:Most studies had shown a linear relationship between serum albumin (sALB) and the prevalence of diabetic retinopathy (DR). Thus, the purpose of this study is to investigate whether their relationship is non-linear. METHODS:We included 426 patients with type 2 diabetes who were hospitalized in Guangdong Provincial People's Hospital from December 2017 to November 2018. The outcome was the prevalence of DR. A two-piecewise logistics regression model was performed to identify the non-linear relationship between sALB and the prevalence of DR. The inflection point was calculated to determine the saturation effect through the maximum likelihood ratio and a recursive algorithm. RESULTS:DR was diagnosed in 167 of 426 type 2 diabetic patients. The relationship between sALB and DR was nonlinear. When sALB was less than 38.10 g/L, a significant negative association was observed (OR = 0.82; 95% CI, 0.72-0.94; P = 0.0037), while no significant association was observed when sALB was greater than 38.10 g/L (OR = 1.12; 95% CI, 0.92-1.35; P = 0.2637). CONCLUSIONS:The relationship between sALB and the prevalence of DR is non-linear. sALB is negatively associated with the prevalence of DR when sALB is less than 38.10 g/L. Our findings need to be confirmed by further prospective research.
10.1186/s12886-024-03348-2
Association between albuminuria and retinal microvascular parameters measured with swept-source optical coherence tomography angiography in patients with diabetic retinopathy.
PloS one
PURPOSE:To evaluate the relationship between urine albumin excretion (UAE) and retinal microvascular parameters assessed using swept-source optical coherence tomography angiography (SS-OCTA) in patients with diabetic retinopathy (DR). METHODS:This retrospective cross-sectional study included 180 patients with diabetes and 50 age-matched controls. Patients with diabetes were grouped according to the five-stage DR severity, combined with the presence of albuminuria. All subjects underwent 12×12mm2 field SS-OCTA. The foveal avascular zone metrics, vessel density, and capillary nonperfusion area (NPA) were quantified using a semi-automatic software algorithm on three different rectangular fields (3×3 mm2, 6×6 mm2, and 10×10 mm2). The correlations between albuminuria and the four OCTA parameters were analyzed. RESULTS:A total of 105 subjects had normal UAE, and 75 subjects had albuminuria. Of the 102 subjects whose DR severity was higher than mild non-proliferative DR (NPDR), capillary NPA on the 3×3 mm2, 6×6 mm2, and 10×10 mm2 fields was significantly larger in the albuminuria group. None of the OCTA parameters were significantly different between the two groups in subjects with mild NPDR or without DR. Multiple logistic regression analysis showed that an increase in NPA in the 6×6 mm2 and 10×10 mm2 fields was a significant risk factor for the presence of albuminuria (odds ratio = 1.92 and 1.35). CONCLUSION:An increase in capillary NPA was independently associated with albuminuria in patients with clinically significant DR levels. SS-OCTA imaging can be a useful marker for the early detection of diabetic nephropathy.
10.1371/journal.pone.0295768
Circulating level of homocysteine contributes to diabetic retinopathy associated with dysregulated lipid profile and impaired kidney function in patients with type 2 diabetes mellitus.
Eye (London, England)
BACKGROUND:To test the hypothesis that elevated plasma levels of homocysteine (Hcy) and lipoprotein (a) (LPA) contribute to diabetic retinopathy (DR) associated with dysregulated lipid profile, dyslipidaemia, and kidney function. METHODS:A total of 83 patients with type 2 diabetes mellitus (T2DM) were enrolled in this prospective case-control study. Patients were categorized into those with no DR (DM), non-proliferative DR (NPDR), and proliferative DR (PDR). Age and sex-matched individuals with no diabetes were included in the control group. Biochemical tests, including fasting blood glucose (FBG), glycated hemoglobin (HbA1c), Hcy, LPA, lipid profile, and urine microalbumin (UMA), were evaluated. RESULTS:Hcy was negatively correlated with high-density lipoprotein-cholesterol (HDL-C) (p < 0.05), but positively correlated with [total cholesterol (TC)-HDL-C)/HDL-C] (p < 0.05), low-density lipoprotein cholesterol (LDL-C)/HDL-C (p < 0.05), and UMA (p < 0.05). Traditional risk factors, Hcy, arteriosclerosis-associated plasma indices, and UMA, resulted as the independent risk factors for the occurrence of DM and DR. After controlling for age, sex, duration of DM, and FBG, a multiple ordinal logistic regression model showed that LPA [OR = 2.90, 95% confidence interval (95% CI) 1.16-7.23, p = 0.023)], LDL-C (OR = 4.28, 95% CI 1.24-14.79, p = 0.021), and (TC-HDL-C)/HDL-C (OR = 1.92, 95% CI 1.05-3.53, p = 0.035) were risk factors for DM and DR. CONCLUSIONS:Hcy and LPA contributed to DM and DR. Hcy was positively correlated with kidney dysfunction and the ratios of lipid profiles, and negatively with HDL-C, LPA, LDL-C, and (TC-HDL-C)/HDL-C resulted as predictors of the occurrence of DM and severity of DR.
10.1038/s41433-022-02144-w
Association between AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes: a cross-sectional investigation.
Frontiers in endocrinology
Objective:This study aimed to explore the association between the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) and diabetic retinopathy (DR) in patients with type 2 diabetes. Methods:In this cross-sectional study, clinical data from 3002 patients with type 2 diabetes admitted to the Department of Endocrinology of our hospital between January 1, 2021, and December 1, 2022, were retrospectively collected. Measurements of AST and ALT were conducted and diabetes-related complications were screened. The association between AST/ALT ratio and diabetic retinopathy was assessed using multivariate logistic regression, and a generalized additive model (GAM) was used to investigate nonlinear relationships. Subgroup analyses and interaction tests were also conducted. Results:Among the 3002 patients, 1590 (52.96%) were male and 1412 (47.04%) were female. The mean AST/ALT ratio was 0.98 ± 0.32, ranging from 0.37 (Min) to 2.17 (Max). Diabetic retinopathy was present in 40.47% of the patients. After multivariate adjustments, for each 0.1 unit increase in AST/ALT ratio, the risk of DR increased by 4% (OR = 1.04, 95% CI: 1.01-1.07, p=0.0053). Higher AST/ALT ratio quartiles were associated with Higher prevalence of DR (OR . Q1: Q4 = 1.34 (CI: 1.03-1.75, p=0.0303).The GAM and smoothed curve fit indicated a linear relationship between AST/ALT ratio and DR risk, with no significant interaction effects across different subgroups. Conclusion:Our study demonstrates a positive correlation between the AST/ALT ratio and diabetic retinopathy risk in type 2 diabetes, suggesting its potential role in assessing DR risk.
10.3389/fendo.2024.1361707
Association Between Triglyceride-Glucose Index and Diabetic Retinopathy: A Meta-Analysis.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
The objective of this study was to assess the relationship between the triglyceride-glucose (TyG) index, a recently proposed marker of insulin resistance, and the occurrence of diabetic retinopathy (DR), a complication associated with cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between the TyG index and DR. To achieve the objective of the meta-analysis, an extensive search was conducted on databases such as PubMed, Embase, and Web of Science to identify observational studies with longitudinal follow-up. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. Twelve observational studies from 11 reports were included in the meta-analysis, which involved 16 259 patients with type 2 diabetes (T2D). Among them, 4302 (26.5%) were diagnosed as DR. Pooled results showed that a higher TyG index was associated with a higher risk of DR [odds ratio (OR) for the fourth versus the first quartile of TyG index: 1.91, 95% confidence interval (CI): 1.44 to 2.53, p<0.001; I2=72%]. Meta-analysis of TyG index analyzed in continuous variable showed consistent results (OR for per 1 unit increment of TyG index: 1.41, 95% CI: 1.08 to 1.86, p=0.01; I2=82%). Subgroup analysis showed that adjustment of HbA1c or the duration of diabetes did not significantly affect the results (p for subgroup difference all>0.05). In conclusion, a high TyG index was associated with the risk of DR in T2D patients.
10.1055/a-2279-7112
Association Between Triglyceride-Glucose Index and Waist-To-Hip Ratio with Type 2 Diabetic Retinopathy in the Chinese Population: A Cross-Sectional Study.
Endocrine research
BACKGROUND:The triglyceride-glucose (TyG) index serves as a convenient indicator of insulin resistance, which has been demonstrated to be associated with diabetic retinopathy(DR). However, the relationship between TyG-WHR, a novel index combining TyG with the central obesity indicator WHR, and retinopathy in patients with type 2 diabetes remains unclear. Therefore, this study aims to investigate the correlation between TyG-WHR and DR in adult patients with type 2 diabetes. METHODS:This cross-sectional study included 1702 patients with T2DM. Logistic regression analysis was performed to examine the associations between TyG-WHR and DR. Additionally, the receiver operating characteristic curve (ROC curve) was utilized to assess the predictive efficacy of TyG-WHR for DR. RESULTS:Patients in higher TyG-WHR quartiles demonstrated an increased presence of DR, and TyG-WHR increased with the severity of DR. Moreover, TyG-WHR remained significantly associated with a higher odds ratio (OR) for DR (OR 1.223, 95% confidence interval [CI] 1.078-1.387, < 0.05) after multivariate adjustment. Additionally, receiver operating characteristic curve analysis indicated that the optimal cutoff value for TyG-WHR in predicting DR presence was 8.8983, with a sensitivity of 61.00%, specificity of 48.50%, and area under the curve (AUC) of 0.555. CONCLUSIONS:In patients with T2DM, TyG-WHR was significantly elevated in those with DR and independently associated with an increased risk of DR presence in Chinese patients. This implies that TyG-WHR could potentially serve as a valuable and dependable biomarker for DR, underscoring the importance of giving greater consideration to T2DM patients with elevated TyG-WHR to effectively prevent and mitigate the onset of DR and associated adverse health outcomes.
10.1080/07435800.2024.2364719
The relationship between diabetic retinopathy and diabetic nephropathy in type 2 diabetes.
Frontiers in endocrinology
Context:Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear. Objective:To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods:Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored. Results:DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN. Conclusion:DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR. Trial registration:ClinicalTrails.gov, NCT03865914.
10.3389/fendo.2024.1292412
Homocysteine and other biochemical parameters in Type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy.
Huang Erh-Jung,Kuo Wei-Wen,Chen Yuh-Jyuan,Chen Ter-Hsin,Chang Mu-Hsin,Lu Min-Chi,Tzang Bor-Show,Hsu Hsi-Hsien,Huang Chih-Yang,Lee Shin-Da
Clinica chimica acta; international journal of clinical chemistry
BACKGROUND:Cardiovascular risk-related markers in type 2 diabetes mellitus (DM) have not been well understood. METHODS:Serum and urine samples for biochemical and immunologic analysis were collected from 204 normal subjects and 257 type 2 DM patients, the latter of which were further classified by different diabetic duration with or without retinopathy. RESULTS:Glycosylated hemoglobin A1c, triglyceride, lipase, free fatty acid, albumin creatinine ratio (ACR), lactate dehydrogenase (LDH) and homocysteine were significantly increased in DM patients, whereas high density lipoprotein cholesterol and bilirubin were significantly decreased in DM patients, compared with normal subjects. Lipid profiles, ACR, bilirubin, uric acid, creatine kinase, and hsCRP were not changed in DM patients with different diabetic duration or diabetic retinopathy. Lactate dehydrogenase in DM patients with duration >20 years and homocysteine in patients with duration >10 years was significantly higher than those with duration <5 years. Homocysteine was significantly increased in DM patients with retinopathy, compared with DM patients without retinopathy. CONCLUSION:The increased triglyceride, lipase, free fatty acid, albumin creatinine ratio, lactate dehydrogenase and homocysteine as well as decreased high density lipoprotein cholesterol and anti-oxidative bilirubin in DM patients should be cautious and considered as risks for increasing DM complication. Homocysteine might be associated with longer diabetic duration and microvascular complication of retinopathy in diabetes.
10.1016/j.cca.2005.10.025
Plasma apelin and asymmetric dimethylarginine levels in type 2 diabetic patients with diabetic retinopathy.
Yonem Arif,Duran Cevdet,Unal Melih,Ipcioglu Osman Metin,Ozcan Omer
Diabetes research and clinical practice
Oxidative stress is thought to be one of the underlying mechanisms of diabetic microvascular complications such as diabetic nephropathy and diabetic retinopathy (DRP). Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and increased by oxidative stress. Apelin is an endogenous ligand for human orphan G-protein-coupled receptor, APJ and increases NO generation. In this study, our aim was to evaluate ADMA and apelin levels in diabetic patients with or without retinopathy and their relationships between retinopathy stages and metabolic parameters. Seventy-nine diabetic patients were included into the study and classified into three groups. Group 1 consisted of 41 patients with no DRP (NDRP), group 2 consisted of 23 patients with nonproliferative DRP (NPDRP), and group 3 consisted of 15 patients with proliferative DRP (PDRP). Plasma ADMA and apelin levels were found to be similar in all groups. But, there was a positive correlation between apelin levels and urinary albumin/creatinine ratio. Further studies involving larger patients populations and healthy controls should be done to clarify the pathogenetic significance of ADMA and apelin in diabetic microvascular complications.
10.1016/j.diabres.2009.03.001
Circulating amino acids and the risk of macrovascular, microvascular and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE trial.
Diabetologia
AIMS/HYPOTHESES:We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. METHODS:We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. RESULTS:In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p < 0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). CONCLUSIONS/INTERPRETATION:We report distinct associations between circulating amino acids and risk of different major complications of diabetes. Low tyrosine appears to be a marker of microvascular risk in individuals with type 2 diabetes independently of fundamental markers of kidney function.
10.1007/s00125-018-4619-x
Association of Serum Ferritin Levels with Microalbuminuria, Glycemic Control and Dyslipidemia.
Dubey K, Usman K, Chaudhary S C, Sawlani K K, Verma S K, Ali W
UNLABELLED: As diabetes is on the rise worldwide, early screening and detection of its complications is crucial. The first clinical sign of renal dysfunction in diabetes is microalbuminuria. Ferritin may have a possible role in the development and prediction of microalbuminuria and other complications of diabetes by 3 possible mechanisms- 1) it is a marker of elevated body iron stores. 2) acts as acute-phase reactant and elevation reflects inflammation 3) Delayed clearance of glycosylated ferritin in patients with diabetes causes raised ferritin levels. In this premise, we studied the association between serum ferritin levels and microalbuminuria, glycemic control and dyslipidemia in type 2 diabetic patients. MATERIAL: A cross-sectional study was carried out at a tertiary hospital in northern India involving 152 patients of type 2 diabetes mellitus. Anthropometric measurements (weight, height), sample collection for basic laboratory parameters including complete blood count, kidney function tests, liver function tests, HbA1c, lipid profile, serum iron and ferritin levels, urinary albumin- creatinine ratio was done. A fundus examination was performed. Results were analyzed using descriptive statistics and making comparisons among various groups. Categorical data were summarized as proportions or percentages while discrete as mean. Chi-square test was used for testing associations. OBSERVATION: Mean serum ferritin levels were significantly higher in patients having microalbuminuria as against patients having normal urinary albumin- creatinine ratio (539 vs 292, p-value- 0.04). Patients having poor glycemic control (HbA1c > 7) had higher ferritin levels (p-value- 0.024). There was a near-significant association (p-value-0.06) between serum ferritin and triglyceride levels. More cases with raised serum ferritin had higher triglyceride levels. Patients having microalbuminuria had a higher prevalence of diabetic retinopathy (p-value- 0.003) and higher triglyceride levels (p-value- 0.041). CONCLUSION: Ferritin can act as a marker of diabetic nephropathy, poor glycemic control and dyslipidemia in type 2 diabetic patients. Our study, therefore, indicates that programs to prevent complications of diabetes would be more effective by placing greater emphasis on patients having higher ferritin levels.
Correlation study of renal function indices with diabetic peripheral neuropathy and diabetic retinopathy in T2DM patients with normal renal function.
Frontiers in public health
Background:The anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of these complications. This study aims to investigate the association between renal function-related indicators and the occurrence of peripheral neuropathy and retinopathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) who currently have normal renal function. Methods:Patients with T2DM who met the criteria were selected from the MMC database and divided into diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR) groups, with a total of 859 and 487 patients included, respectively. Multivariate logistic regression was used to analyze the relationship between blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), urine albumin(ALB), albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and diabetic peripheral neuropathy and retinopathy. Spearman correlation analysis was used to determine the correlation between these indicators and peripheral neuropathy and retinopathy in diabetes. Results:In a total of 221 patients diagnosed with DPN, we found positive correlation between the prevalence of DPN and eGFR (18.2, 23.3, 35.7%, < 0.05). Specifically, as BUN (T1: references; T2:OR:0.598, 95%CI: 0.403, 0.886; T3:OR:1.017, 95%CI: 0.702, 1.473; < 0.05) and eGFR (T1: references; T2:OR:1.294, 95%CI: 0.857, 1.953; T3:OR:2.142, 95%CI: 1.425, 3.222; < 0.05) increased, the odds ratio of DPN also increased. Conversely, with an increase in Cr(T1: references; T2:OR:0.86, 95%CI: 0.56, 1.33; T3:OR:0.57, 95%CI: 0.36, 0.91; < 0.05), the odds ratio of DPN decreased. Furthermore, when considering sensitivity and specificity, eGFR exhibited a sensitivity of 65.2% and specificity of 54.4%, with a 95% confidence interval of 0.568-0.656. Conclusion:In this experimental sample, we found a clear positive correlation between eGFR and DPN prevalence.
10.3389/fpubh.2023.1302615
Prophylactic role of taurine and its derivatives against diabetes mellitus and its related complications.
Sarkar Poulami,Basak Priyanka,Ghosh Sumit,Kundu Mousumi,Sil Parames C
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Taurine is a conditionally essential amino acid present in the body in free form. Mammalian taurine is synthesized in the pancreas via the cysteine sulfinic acid pathway. Anti-oxidation and anti-inflammation are two main properties through which it exerts its therapeutic effects. Many studies have shown its excellent therapeutic potential against diabetes mellitus and related complications like diabetic neuropathy, retinopathy, nephropathy, hematological dysfunctions, reproductive dysfunctions, liver and pancreas related complications etc. Not only taurine, a number of its derivatives have also been reported to be important in ameliorating diabetic complications. The present review has been aimed to describe the importance of taurine and its derivatives against diabetic metabolic syndrome and related complications.
10.1016/j.fct.2017.10.022
Relationship between renal and liver function with diabetic retinopathy in patients with type 2 diabetes mellitus: a study based on cross-sectional data.
Scientific reports
This study aims to explore the relationship between abnormal renal- and liver-function and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 994 T2DM patients who received inpatient treatment in the Endocrinology Department of Henan Province People's Hospital were included in the study. Logistic regression was performed to identify the relationship between abnormal renal and liver function with DR. Receiver operator characteristic analysis was performed to explore the efficacy of risk factors in predicting DR. Higher urine albumin [OR(95%CI) = 3.344(1.921-5.822), P < 0.001] and urine albumin/creatinine ratio [OR (95%CI) = 2.901(1.911-5.822), P < 0.001] were closely related to the occurrence of DR. People with low TP had a 1.624-times higher risk (95%CI: 1.008-2.617) of developing DR than those with normal total protein (P = 0.046). The more risk factors that are present, the greater the risk of DR. For every one-point incremental increase in the risk-factor score, the risk of DR increased by 31.0% (P < 0.001). The area under receiver operating curve of risk-factor score was 0.839 (0.812, 0.866), with a sensitivity of 81.9% and a specificity of 74.8%. The risk of developing DR increased with an increased risk-factor score. These findings are potentially valuable for DR screening and early diagnosis in patients with T2DM.
10.1038/s41598-022-13164-7
Causal associations between liver enzymes and diabetic microvascular complications: A univariable and multivariable Mendelian randomization.
PloS one
BACKGROUND:Observational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications. METHODS:Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses. RESULTS:UVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications. CONCLUSIONS:Robust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention.
10.1371/journal.pone.0296894
Prediction and analysis of risk factors for diabetic retinopathy based on machine learning and interpretable models.
Heliyon
Objective:Diabetic retinopathy is one of the major complications of diabetes. In this study, a diabetic retinopathy risk prediction model integrating machine learning models and SHAP was established to increase the accuracy of risk prediction for diabetic retinopathy, explain the rationality of the findings from model prediction and improve the reliability of prediction results. Methods:Data were preprocessed for missing values and outliers, features selected through information gain, a diabetic retinopathy risk prediction model established using the CatBoost and the outputs of the mode interpreted using the SHAP model. Results:One thousand early warning data of diabetes complications derived from diabetes complication early warning dataset from the National Clinical Medical Sciences Data Center were used in this study. The CatBoost-based model for diabetic retinopathy prediction performed the best in the comparative model test. ALB_CR, HbA, UPR_24, NEPHROPATHY and SCR were positively correlated with diabetic retinopathy, while CP, HB, ALB, DBILI and CRP were negatively correlated with diabetic retinopathy. The relationships between HEIGHT, WEIGHT and ESR characteristics and diabetic retinopathy were not significant. Conclusion:The risk factors for diabetic retinopathy include poor renal function, elevated blood glucose level, liver disease, hematonosis and dysarteriotony, among others. Diabetic retinopathy can be prevented by monitoring and effectively controlling relevant indices. In this study, the influence relationships between the features were also analyzed to further explore the potential factors of diabetic retinopathy, which can provide new methods and new ideas for the early prevention and clinical diagnosis of subsequent diabetic retinopathy.
10.1016/j.heliyon.2024.e29497
Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis.
Cardiovascular diabetology
OBJECTIVE:The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings. METHODS:A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS:A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82-2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32-1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74-4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48-3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31-4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57-1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74-0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88-2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12-1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38-3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22-1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12-1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57-1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25-1.85). CONCLUSION:The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index.
10.1186/s12933-024-02392-y
Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema.
Boehm B O,Schilling S,Rosinger S,Lang G E,Lang G K,Kientsch-Engel R,Stahl P
Diabetologia
AIMS/HYPOTHESIS:Diabetic retinopathy is a frequent microvascular complication. In search of novel risk markers, we analysed the association between serum levels of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML) and prevalence of advanced stages of retinopathy in Type 2 diabetic patients without nephropathy. METHODS:We carried out a case-control study of Type 2 diabetic patients with and without advanced stages of diabetic retinopathy. Retinopathy and macular oedema were defined according to standard criteria. Serum levels of CML were estimated by means of a novel competition-based ELISA assay. RESULTS:Serum levels of CML were significantly different between age-matched controls (n=792; mean value +/- SD: 521+/-134 ng/ml), Type 2 diabetic patients without severe retinopathy (821+/-141 ng/ml; p<0.0001) and Type 2 diabetic patients with proliferative retinopathy (1182+/-346 ng/ml; p<0.0001). Levels of CML greater than 1000 ng/ml represented a 25-fold increase in risk of proliferative retinopathy. Receiver operating characteristics analysis revealed a CML threshold of 1087 ng/ml (100% sensitivity, 93% specificity) for clinically significant macular oedema. CONCLUSIONS/INTERPRETATION:High serum levels of CML were associated with advanced stages of retinopathy. Serum levels were shown to be a progressive risk marker, whereby a level of more than 1000 ng/ml induced a 25-fold increase in risk of proliferative retinopathy and clinically significant macular oedema. Our data suggest that serum levels of CML provide a novel risk marker for advanced stages of diabetic retinopathy in Type 2 diabetic patients.
10.1007/s00125-004-1455-y
The Intersection of Serine Metabolism and Cellular Dysfunction in Retinal Degeneration.
Sinha Tirthankar,Ikelle Larissa,Naash Muna I,Al-Ubaidi Muayyad R
Cells
In the past, the importance of serine to pathologic or physiologic anomalies was inadequately addressed. Omics research has significantly advanced in the last two decades, and metabolomic data of various tissues has finally brought serine metabolism to the forefront of metabolic research, primarily for its varied role throughout the central nervous system. The retina is one of the most complex neuronal tissues with a multitude of functions. Although recent studies have highlighted the importance of free serine and its derivatives to retinal homeostasis, currently few reviews exist that comprehensively analyze the topic. Here, we address this gap by emphasizing how and why the de novo production and demand for serine is exceptionally elevated in the retina. Many basic physiological functions of the retina require serine. Serine-derived sphingolipids and phosphatidylserine for phagocytosis by the retinal pigment epithelium (RPE) and neuronal crosstalk of the inner retina via D-serine require proper serine metabolism. Moreover, serine is involved in sphingolipid-ceramide balance for both the outer retina and the RPE and the reductive currency generation for the RPE via serine biosynthesis. Finally and perhaps the most vital part of serine metabolism is free radical scavenging in the entire retina via serine-derived scavengers like glycine and GSH. It is hard to imagine that a single tissue could have such a broad and extensive dependency on serine homeostasis. Any dysregulation in serine mechanisms can result in a wide spectrum of retinopathies. Therefore, most critically, this review provides a strong argument for the exploration of serine-based clinical interventions for retinal pathologies.
10.3390/cells9030674
Implication of Hyperhomocysteinemia in Blood Retinal Barrier (BRB) Dysfunction.
Tawfik Amany,Samra Yara A,Elsherbiny Nehal M,Al-Shabrawey Mohamed
Biomolecules
Elevated plasma homocysteine (Hcy) level, known as hyperhomocysteinemia (HHcy) has been linked to different systemic and neurological diseases, well-known as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and has been identified as a risk factor for several ocular disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Different mechanisms have been proposed to explain HHcy-induced visual dysfunction, including oxidative stress, upregulation of inflammatory mediators, retinal ganglion cell apoptosis, and extracellular matrix remodeling. Our previous studies using in vivo and in vitro models of HHcy have demonstrated that Hcy impairs the function of both inner and outer blood retinal barrier (BRB). Dysfunction of BRB is a hallmark of vision loss in DR and AMD. Our findings highlighted oxidative stress, ER stress, inflammation, and epigenetic modifications as possible mechanisms of HHcy-induced BRB dysfunction. In addition, we recently reported HHcy-induced brain inflammation as a mechanism of blood-brain barrier (BBB) dysfunction and pathogenesis of Alzheimer's disease (AD). Moreover, we are currently investigating the activation of glutamate receptor -methyl-d-aspartate receptor (NMDAR) as the molecular mechanism for HHcy-induced BRB dysfunction. This review focuses on the studied effects of HHcy on BRB and the controversial role of HHcy in the pathogenesis of aging neurological diseases such as DR, AMD, and AD. We also highlight the possible mechanisms for such deleterious effects of HHcy.
10.3390/biom10081119
Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.
Scientific reports
To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.
10.1038/s41598-021-88104-y
Plasma homocysteine levels are associated with macular thickness in type 2 diabetes without diabetic macular edema.
Dong Ning,Shi Hong,Tang Xin
International ophthalmology
PURPOSE:To explore the relationships between macular thickness and the plasma concentrations of homocysteine, vitamin B12, folate, and other known risk factors for patients with diabetes without diabetic macular edema (DME). METHODS:Fasting venous blood samples were collected from 252 subjects (126 relatively healthy subjects with type 2 diabetes without diabetic macular edema and 126 age- and gender-matched controls). Measurement of macular thickness and volume was performed for those subjects using SD-OCT. The plasma concentrations of homocysteine, vitamin B12, folate, and other known risk factors were analyzed in all the patients and controls using multiple linear regression models. RESULTS:An increase in the serum levels of homocysteine was present within patients with type 2 diabetes compared to healthy individuals. The mean total plasma homocysteine levels were associated with a greater central subfield macular thickness (CSMT), average macular thickness (AMT), and average macular volume (AMV) in patients with type 2 diabetes without DME, after adjusting for age, sex, duration of diabetes, and HbA1c. Each 1 mmol/L increase in tHcy level was associated with a 6.57 µm greater CSMT (95% confidence interval [CI] 1.78, 11.36), a 4.51 µm greater AMT (95% CI 1.05, 7.98), and a 4.72 mm greater AMV (95% CI 1.23, 8.21). CONCLUSIONS:Higher homocysteine levels were associated with an increased CSMT, AMT, and AMV in diabetic patients without DME. This link may indicate that patients with type 2 diabetes with increased levels of plasma tHcy are more prone to develop a clinical manifestation of DME.
10.1007/s10792-017-0528-0
Circulating glutamine/glutamate ratio is closely associated with type 2 diabetes and its associated complications.
Frontiers in endocrinology
Objective:This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications. Methods:Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators. Results:Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c ( = -0.228, = 0.017). Furthermore, HOMA-β exhibited a negative correlation with Glu ( = -0.301, = 0.003) but a positive correlation with Gln/Glu ( = 0.245, = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15). Conclusion:The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications.
10.3389/fendo.2024.1422674
Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia.
Frontiers in molecular biosciences
Introduction:Multifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment. Methods:The electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study's design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites. Results:Metabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism Conclusion:This review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.
10.3389/fmolb.2024.1403844
An Investigation of the Correlation Between Retinal Nerve Fiber Layer Thickness with Blood Biochemical Indices and Cognitive Dysfunction in Patients with Type 2 Diabetes Mellitus.
Diabetes, metabolic syndrome and obesity : targets and therapy
Objective:The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications. Methods:Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels. Patients who met the inclusion criteria were divided as the diabetic retinopathy (DR) group (n=46) and simple diabetes group (n=34). The RNFLT, blood biochemical indexes and changes in cognitive functions of the patients were detected. The correlation between RNFLT with blood biochemical indexes and cognitive dysfunction was analyzed. Results:Compared with the simple diabetes group, patients in the DR group had much lower mean, nasal, inferior and superior thicknesses (<0.01). There existed no significant difference in blood pressure, body mass index (BMI), blood lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) between the two groups (>0.05). Compared with the simple diabetes group, patients in the DR group had much higher fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FINS), insulin resistance (HOMA-IR) index, apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) (<0.001). Besides, the DR group had sharply lower scores on the Mini-Mental State Examination (MMSE) scale and higher levels of the Trail Making Test-A (TMT-A) and TMT-B (<0.001). Spearman correlation analysis confirmed that the mean RNFLT was negatively correlated with the levels of FBG, HbA1c, HOMA-IR index, TMT-A and TMT-B (<0.05), positively correlated with the score of mini-mental state examination (MMSE) (<0.05), and was no significant correlation with FINS and ApoB/ApoA1 (>0.05). Conclusion:DR patients had significantly reduced RNFLT, elevated levels of blood glucose related indicators, and cognitive dysfunction. There existed a correlation between RNFLT and FBG, HbA1c, HOMA-IR index, TMT-A, TMT-B and MMSE.
10.2147/DMSO.S470297
Correlation of glucose and lipid metabolism, renal function and retinopathy in diabetic retinopathy patients using OCTA detection.
American journal of translational research
OBJECTIVE:To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS:A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS:Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all <0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, <0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (<0.05). CONCLUSION:Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.
10.62347/WFUF5719
Dynamic observation and analysis of factors influencing the progression of diabetic retinopathy.
Experimental gerontology
OBJECTIVE:To actively monitor and analyze the factors that affect the advancement of diabetic retinopathy (DR). METHOD:In this study, we prospectively recruited patients diagnosed with non-proliferative diabetic retinopathy (NPDR) for concurrent monitoring. A total of 75 patients who transitioned from NPDR to proliferative diabetic retinopathy (PDR) comprised the progression group, while 112 NPDR patients who did not develop PDR formed the stable group in a prospective cohort study. Follow-up assessments occurred every six months, and patients were observed continuously over an eight-year period. Clinical parameters from both NPDR and PDR groups were collected to assess the stability of these indicators (with a coefficient of variation [CV] > 5 % indicating instability and CV < 5 % indicating stability). RESULTS:In the NPDR cohort, 80.4 % Control the stability ratio regulation of glycosylated hemoglobin (HbA1c), whereas in the PDR cohort, 80.0 % Control the proportion of instability (P = 0.001); for blood creatinine (Cr), 64.3 % of NPDR patients maintained stable levels, contrasting with 77.3 % of PDR patients with fluctuating levels (P = 0.001). Blood urea nitrogen (BUN) and homocysteine (HCY) control demonstrated instability in both NPDR and PDR groups. Instability in regulating HbA1c, Cr, BUN, and HCY served as independent risk factors for DR progression, with significant associations found between HbA1c CV (HR: 15.586; 95 % CI: 14.205-15.988; p = 0.001), Cr CV (HR: 9.231; 95 % CI: 9.088-10.235; p = 0.005), BUN CV (HR: 3.568; 95 % CI: 3.183-4.367; p = 0.01), and HCY CV (HR: 8.678; 95 % CI: 7.754-8.998；p = 0.003). CONCLUSION:Inadequate regulation of HbA1c, Cr, BUN, and HCY independently impact the advancement of DR.
10.1016/j.exger.2024.112581
Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy.
World journal of diabetes
BACKGROUND:No study has investigated the change regularity between age and subfoveal choroidal thickness (SFCT) in proliferative diabetic retinopathy (PDR). AIM:To investigate the relationship between the SFCT and age in Chinese patients with PDR. METHODS:This was a cross-sectional retrospective study. The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR. Con-tralateral eyes that met the criteria were included in the study. All necessary laboratory tests were performed at the time of admission. Central macular thickness (CMT) and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography. CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software. RESULTS:The final analysis included a total of 234 individuals with PDR. The average age was 55.60 years old ± 10.03 years old, and 57.69% of the population was male. Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR [β = -2.44, 95% confidence interval (95%CI): -3.46 to -1.42; < 0.0001]. In the fully adjusted model, the correlation between SFCT and age remained steady (β = -1.68, 95%CI: -2.97 to -0.39; = 0.0117). Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear, with an inflection point at 54 years of age. CONCLUSION:Our findings suggest that age is a key determinant of choroidal thickness. The non-linear link between SFCT and age in PDR patients should be taken into account.
10.4239/wjd.v15.i9.1903
Sex Differences in Inflammation-Related Biomarkers Detected with OCT in Patients with Diabetic Macular Edema.
Ophthalmology science
Purpose:To investigate sex-based differences in inflammation-related biomarkers on spectral-domain OCT. Design:Cross-sectional study. Participants:Patients with diabetic macular edema (DME) between February 1, 2019, and March 31, 2023, without intravitreal anti-VEGF injection within the previous 6 months. Methods:We reviewed each patient's medical record for age, biological sex, race and ethnicity, most recent glycated hemoglobin A1c (HbA1c) level, visual acuity (VA), and central macular thickness (CMT). OCT biomarkers that have been found in literature to be associated with inflammation, including disorganization of retinal inner layers (DRIL), retinal hyperreflective retinal foci (HRFs), hyperreflective choroidal foci (HCFs), subfoveal neuroretinal detachment (SND), and perturbation in retinal nerve fiber layer thickness, ganglion cell layer thickness, and inner nuclear layer (INL) thickness were evaluated by graders masked to the clinical characteristics of the patients. We performed multivariable regression analyses with the OCT biomarkers as the outcome variables and sex, age, HbA1c, and CMT as independent variables. Main Outcome Measures:OCT inflammation-related biomarkers, as listed above. Results:Female patients were, on average, 2 years older than male patients ( = 0.041). There were no significant differences in race and ethnicity, HbA1c, VA, or CMT between male and female patients. After controlling for age, HbA1c, and CMT, we found male sex to be associated with more HRF (incidence rate ratio [IRR] = 1.19; 95% confidence interval [CI] = 1.10-1.29), more HCF (odds ratio = 2.01; 95% CI = 1.12-3.64), and thicker INL (7 μm thicker in males; 95% CI = 2-12). Sex was not a significant predictor for either DRIL or SND in the multivariable regression models. Patients with higher HbA1c were more likely to have more HRF (IRR = 1.02 per 1 point increase; 95% CI = 1.00-1.04) after controlling for other factors. Conclusions:Male sex was correlated with more inflammation-related biomarkers on OCT including more HRF, more HCF, and thicker INL, after accounting for age, glycemic control, and amount of DME. Further studies are needed to evaluate the potential implications of these sex-based differences for individualized treatment. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
10.1016/j.xops.2024.100580
A spectral domain optical coherence tomography (SD-OCT) study of intraretinal hyperreflective foci and its relationship with visual acuity and grades of retinopathy among patients of diabetes mellitus in Indian population.
Medical journal, Armed Forces India
Background:Hyperreflective foci (HRF) are biomarkers in detection of diabetic retinopathy (DR). Presence of HRF on spectral domain optical coherence tomography (SD-OCT) can give a correlation with visual acuity change and grades of DR. Purpose of this study is to determine the presence, location, and role of HRF in the retina of DM patients with and without retinopathy. Methods:A total of 192 eyes of patients suffering from type II DM were evaluated. Patients were divided into 2 groups, with Group A having diabetes without retinopathy (20 patients) and group B (76 patients) having diabetes and various grades of retinopathy. SD-OCT was performed in all patients, passing through the center of fovea. On OCT, presence and absence of HRF were noted. Characteristics of the hyper-reflective spots were evaluated: location, shape, size, back shadowing and association with central macular thickness (CMT), visual acuity, and grades of retinopathy. Results:HRF were present in 169 eyes (88%) out of 192 eyes. The shape and location of HRF tend to change with disease progression. HRF were significantly associated with increasing grades of retinopathy (χ2 = 57.586, p < 0.01) Association of macular edema was significant with both retinopathy (χ2 = 8.895, p < 0.05) and HRF (χ2 = 34.720, p < 0.01). Association of best-corrected visual acuity with HRF (χ2 = 21.232, p < 0.01), macular edema (χ2 = 86.960, p < 0.01), and CMT (χ2 = 47.959, p< 0 .01) was significant. Conclusion:HRF is a great indicator for early diagnosis of subclinical retinopathy and can be used to monitor the progression of disease and development of macular edema. Significant difference is present in HRF distribution and morphology.
10.1016/j.mjafi.2024.04.019
Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy.
Srivastav Khushboo,Saxena Sandeep,Mahdi Abbas A,Shukla Rajendra K,Meyer Carsten H,Akduman Levent,Khanna Vinay K
Molecular vision
PURPOSE:To study the correlation between serum levels of vitamin B, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). METHODS:In a tertiary care center-based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40-65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. RESULTS:Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). CONCLUSIONS:This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy.
Plasma homocysteine and macular thickness in older adults-the Rugao Longevity and Aging Study.
Eye (London, England)
OBJECTIVES:To determine the association of plasma homocysteine levels with retinal layer thickness in a large community cohort of older adults. METHODS:The Rugao Longevity and Ageing Study is an observational, prospective and community-based cohort study. A total of 989 older adults who underwent spectral-domain optical coherence tomography (SD-OCT) were included and analyzed. Foveal, macular retinal nerve fibre layer (mRNFL) and ganglion cell layer plus inner plexiform layer (GC-IPL) thicknesses were measured by SD-OCT. Plasma homocysteine levels were measured using chemiluminescence immunoassay. Linear regression analyses were performed to evaluate the relationship between plasma homocysteine and retinal layer thickness while controlling for confounding factors. RESULTS:Of the 989 participants, 500 (50.56%) were men. The mean age was 78.26 (4.58) years, and the mean plasma homocysteine level was 16.38 (8.05) μmol/L. In multivariable analyses, each unit increase in plasma homocysteine was associated with an 8.84 × 10 (95% CI: -16.54 × 10 to -1.15 × 10, p = 0.032) μm decrease in the average inner thickness of the GC-IPL after controlling for confounding factors. The association remained significant even in participants without major cardiovascular disease or diabetes (β = -10.33 × 10, 95% CI: -18.49 × 10 to -2.18 × 10, p = 0.013). No significant associations of plasma homocysteine levels with macular thickness or mRNFL were found in primary and sensitivity analyses (p > 0.05). CONCLUSIONS:Increased plasma homocysteine levels are associated with a thinner GC-IPL. Plasma homocysteine may be a risk factor for thinner retinas in older adults.
10.1038/s41433-021-01549-3