RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

Uric acid index is a risk for mild cognitive impairment in type 2 diabetes.

BACKGROUND: A new uric acid (UA) index has recently been proposed, while serum uric acid (SUA), fasting triglyceride, and fasting blood glucose levels in the index are shown to affect cognitive function. This study aims to investigate the clinical value of the UA index for assessing mild cognitive impairment (MCI) in type 2 diabetes (T2D) patients. METHODS: This was an observational cross-sectional study with 616 participants. A generalized additive model was used to determine a linear or curvilinear relationship between cognitive performance and the UA index. Logistic regression and random forest models were both developed. A receiver operating characteristic curve (ROC) was delineated and the area under the curve (AUC) was calculated. RESULTS: MCI was diagnosed in 313 participants (50.81%). Compared with the T2D-normal cognitive function group, MCI subjects had higher UA indexes, lower cognitive scores, and lower education levels (p < 0.001). Generalized additive models showed the UA index and the Montreal Cognitive Assessment (MoCA) score to be decreased linearly (p < 0.001). The UA index AUC was 0.751 (95% CI = 0.713-0.789, p < 0.001). The optimal cut-off point for the identification of MCI based on the UA index was 11.26 (sensitivity: 62.3%, specificity: 75.9%). Results for females in the cohort yielded an AUC change of + 2.5%, the less-educated population (AUC change of + 4.7%), and the hypertensive population (AUC change of + 1.1%). The AUCs were 0.791 (95% CI = 0.720-0.863) for the random forest model and 0.804 (95% CI = 0.770-0.837) for the logistic regression model, and no statistical significance was found (p = 0.758). CONCLUSION: This study showed that the increased UA index was independently associated with MCI in patients with T2D, especially among female, less-educated, and hypertensive patients. It could be a potential indicator of MCI in T2D patients.

Relationship Between Index of Cardiac Electrophysiological Balance, Frontal QRS-T Angle and Retinopathy in People with Type 2 Diabetes.

Background: Diabetic retinopathy (DR) is strongly associated with cardiovascular disease, which is a risk factor for sudden cardiac death (SCD). The index of cardiac electrophysiological balance (iCEB) and the frontal QRS-T angle are recommended to predict the risk of ventricular arrhythmias more than other ECG parameters. However, the relationships between these two markers and DR have not yet been explored. The aim of this study was to investigate the variation in the iCEB, corrected iCEB (iCEBc) and frontal QRS-T angle in different stages of DR and determine whether there are associations between these markers and DR. Methods: The sample comprised 665 patients with Type 2 diabetes mellitus (T2DM) who were classified into three groups: no DR (NDR), mild to moderate non-proliferative DR (NPDR), and vision-threatening DR (VTDR). Twelve-lead ECG was performed and the QT, QTc, QRS duration, iCEB, iCEBc and frontal QRS-T angle were recorded and compared across the groups. Results: The VTDR group had a significantly higher iCEBc and frontal QRS-T angle than the NDR and NPDR groups. After controlling for confounding variables, the correlations between the iCEBc (OR=2.217, 95% CI=1.464-3.358, P<0.001), frontal QRS-T angle (OR=1.017, 95% CI=1.008-1.025, P<0.001) and DR risk remained (P<0.05). Subjects in the fourth iCEBc quartile (adjusted OR=2.612, 95% CI=1.411-4.834, p=0.002) had a much higher chance of developing DR compared to those in the first quartile. In comparison to the first frontal QRS-T angle quartile, subjects in the third (adjusted OR=1.998, 95% CI=1.167-3.422, P=0.012) and fourth (adjusted OR=2.430, 95% CI=1.420-4.160, P=0.001) frontal QRS-T angle quartiles had significantly greater risks of DR. Conclusion: With the progression of DR, the iCEBc and frontal QRS-T angle increase. An increased iCEBc and frontal QRS-T angle are associated with an increased risk of DR.

Triglyceride Glucose Index is Related with the Risk of Mild Cognitive Impairment in Type 2 Diabetes.

Background: The triglyceride glucose (TyG) index reflects insulin resistance; the latter being associated with mild cognitive impairment (MCI). Objective: To investigate the clinical value of the TyG index to identify MCI in patients living with type 2 diabetes (T2D) using a cross-sectional study. Methods: This cross-sectional study was performed on 517 patients with T2D. The diagnosis of MCI was based on criteria established by the National Institute on Aging-Alzheimer's Association workgroup, and patients were divided into the MCI group and the normal cognitive function (NCF) group. The logistic regression analysis determines whether the TyG index is related to MCI. Subsequently, we constructed the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). The nomogram model of the influence factor was established and verified. Results: Compared to the type 2 diabetes-normal cognitive function (T2D-NCF) group, the MCI subjects were olderand had higher TyG indexes, lower cognitive scores, and lower education levels (p < 0.01). After adjusting for the confounders, the TyG index was associated with MCI (OR = 7.37, 95% CI = 4.72-11.50, p < 0.01), and TyG-BMI was also associated with MCI (OR = 1.02, 95% CI = 1.01-1.02, p<0.01). The TyG index AUC was 0.79 (95% CI = 0.76-0.83). The consistency index of the nomogram was 0. 83[95% CI (0. 79, 0. 86)]. Conclusion: Our results indicate that the TyG index and TyG-BMI are associated with MCI in T2D patients, and the TyG index is an excellent indicator of the risk of MCI in T2D patients. The nomogram incorporating the TyG index is useful to predict MCI risk in patients with T2D.

Exosomal ncRNAs: Novel therapeutic target and biomarker for diabetic complications.

Exosomes are discoid vesicles with a diameter of 40-160 nm. They are mainly derived from the multivesicular body formed by the invagination of lysosomal particles in the cell, which are released into the extracellular matrix after the fusion of the outer membrane. Exosomes are widespread and distributed in various body fluids, they are rich in nucleic acids (microRNA, lncRNA, circRNA, mRNA, tRNA, etc.), proteins, lipids, etc. As an important mediator of cellular communication, exosomes carry and transmit important signaling molecules and are widely involved in intercellular material transport and information transfer, they regulate cellular physiological activities and are closely related to the occurrence and course of various diseases. In recent years, with the deepening of exosome-related research, we discovered that exosomal non-coding RNAs are associated with diabetic complications such as diabetic retinopathy, diabetic nephropathy, diabetic foot ulcer. This article reviews the new findings of exosomal non-coding RNAs (mainly microRNAs, lncRNAs, circRNAs) in diabetic complications, and analyzes the potential of exosomal ncRNA as new biomarkers and new cell-free therapies in the diagnosis and treatment of diabetic complications, hoping to provide new ideas for the prevention, diagnosis, and treatment of diabetic complications.