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.

Association between the neutrophil to lymphocyte ratio and mild cognitive impairment in patients with type 2 diabetes.

AIM: Evidence indicates that type 2 diabetes (T2D) is associated with mild cognitive impairment (MCI). Inflammation is a recognized sign of many neurodegenerative diseases. The neutrophil-to-lymphocyte ratio (NLR) is a novel and inexpensive marker of inflammation. The purpose of this study was to investigate the relationship between the NLR and MCI in patients with T2D. METHODS: The sample for this study comprised 787 patients with T2D, including 411 patients with normal cognitive function and 376 patients with MCI. Blood biochemical parameters and routine blood indicators were determined by an automatic analyzer. The NLR was calculated as the neutrophil count divided by the lymphocyte count. RESULTS: Compared with the control group, the MCI group was older and had a higher NLR but a lower education level and Montreal Cognitive Assessment (MoCA) score (p < 0.05). Spearman correlation and multiple linear regression analyses confirmed that the MoCA score was negatively associated with the NLR (p < 0.001). Multivariate logistic regression analysis demonstrated that the NLR was an independent risk factor for MCI in patients with T2D (p < 0.001). After adjusting for confounding factors, the risk of MCI for those in the third tertile of the NLR was 2.907 times higher than that of those in the first tertile of the NLR (OR = 2.907, 95%CI = 1.978-4.272, p < 0.001). CONCLUSION: An elevated NLR is associated with MCI 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.

High remnant cholesterol level is relevant to diabetic retinopathy in type 2 diabetes mellitus.

BACKGROUND: Diabetic retinopathy (DR) is the primary oculopathy causing blindness in diabetic patients. Currently, there is increasing interest in the role of lipids in the development of diabetic retinopathy, but it remains controversial. Remnant cholesterol (RC) is an inexpensive and easily measurable lipid parameter; however, the relationship between RC and DR in type 2 diabetes mellitus (T2DM) has not been elucidated. This research investigates the relevance between RC levels and DR severity while building a risk prediction model about DR. METHODS: In this single-centre retrospective cross-sectional study. Each hospitalised T2DM patient had no oral lipid-lowering drugs in the past three months, and coronary angiography showed epicardial coronary artery stenosis of less than 50% and completed seven-field stereo photographs, fluorescein fundus angiography, and optical coherence tomography detection. The RC value is calculated according to the internationally recognised formula. Binary logistic regression was used to correct confounding factors, and the receiver operating characteristic (ROC) analysis was used to identify risk factors and assess the nomogram's diagnostic efficiency. RESULTS: A total of 456 T2DM patients were included in the study. The RC levels in the DR team was higher [0.74 (0.60-1.12) mmo/l vs 0.54 (0.31-0.83) mmol/l P < 0.001] in the non-DR team. After adjusting for confounding elements, RC levels are still associated with DR risk (OR = 5.623 95%CI: 2.996-10.556 P < 0.001). The ratio of DR in every stage (except mild non-proliferative diabetic retinopathy) and DME in the high RC level team were further increased compared to the low-level team (all P < 0.001). After ROC analysis, the overall risk of DR was predicted by a nomogram constructed for RC, diabetes duration, and the neutrophil-lymphocyte ratio as 0.758 (95%CI 0.714-0.802 P < 0.001). CONCLUSIONS: High RC levels may be a potential risk factor for diabetic retinopathy, and the nomogram does better predict DR. Despite these essential findings, the limitation of this study is that it is single-centred and small sample size analysis.

Screening and validation of differentially expressed genes in adipose tissue of patients with obesity and type 2 diabetes mellitus.

White adipose tissue (WAT) plays a pivotal role in the onset of type 2 diabetes mellitus (T2DM) and obesity. Despite its significance the underlying pathogenesis and key genes associated with it remain elusive. In our study, we screened the differentially expressed genes (DEGs) in intra-abdominal WAT of T2DM patients with obesity, as well as those with simple obesity, aiming to lay a foundational theory for an in-depth investigation of T2DM pathogenesis and the identification of novel therapeutic targets. Gene expression datasets (GSE16415 and GSE71416) were retrieved from the Gene Expression Omnibus (GEO) database. We employed R for screening DEGs and conducted a functional enrichment analysis using the Metascape database. Combined Lasso regression and Boruta feature selection algorithms were used to identify key DEGs. Subsequently, these were cross-verified using the GSE29231 dataset. Samples and medical records were collected from clinical study participants. The mRNA and protein expressions of the key DEGs were verified using qRT-PCR and western blotting, respectively. We discerned a total of 130 DEGs, with 40 being upregulated and 90 downregulated. Functional and pathway enrichment analyses illuminated that these genes are instrumental in mediating metabolite and energy production, neutrophil-mediated immunity, and other associated biological processes. This includes their involvement in the tricarboxylic acid cycle, glycolysis/gluconeogenesis, peroxisome proliferator-activated receptors, and other signalling pathways. Two genes, CIDEA and FSCN1 emerged as key DEGs. The low expression of CIDEA and high expression of FSCN1 in the T2DM and obesity group were verified in clinical samples (P < 0.05). We established that CIDEA and FSCN1 manifest significant differential expression in T2DM patients who are obese. This suggests their potential as risk assessment markers and therapeutic targets for T2DM.

Correlation of dietary inflammation index and dietary pattern with mild cognitive impairment in patients with type 2 diabetes.

OBJECTIVE: We aimed to determine the dietary patterns associated with mild cognitive impairment (MCI) in type 2 diabetes (T2DM) and the correlation of dietary inflammatory index (DII) with MCI. METHODS: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. A semi-quantitative food frequency questionnaire was used to collect dietary data and calculate DII. Dietary patterns were determined by reduced-rank regression (RRR), grouping dietary pattern scores and DII into quartiles, with logistic regression for correlation analysis. Dose-response relationships between dietary pattern scores, DII and diabetic MCI were explored using restricted cubic splines (RCS). A mediation analysis was performed to investigate whether DII mediates the association between dietary patterns and MCI. RESULTS: In the "Mediterranean-style dietary pattern", the multivariable-adjusted odds ratio of having MCI was 0.37 (95% CI: 0.20-0.68; p for trend=0.002) in the highest versus lowest quartiles of the dietary score. In the "high-meat and low-vegetable pattern", the multivariable-adjusted odds ratio of having MCI was 6.84 (95% CI: 3.58-13.10; p for trend<0.001) in the highest versus lowest quartiles of the dietary score. In the "Western-style dietary pattern", the multivariable-adjusted odds ratio of having MCI was 2.48 (95% CI: 1.38-4.46; p for trend=0.001). The multivariable-adjusted odds ratio of having MCI was 3.99 (95% CI: 2.14-7.42; p for trend<0.001) in the highest versus lowest quartiles of DII. There is a non-linear dose-response relationship between the "high-meat and low-vegetable pattern" score and the prevalence of MCI, as well as the DII and the prevalence of MCI. The DII partially mediated the impact of the "Mediterranean-style dietary pattern" and the "high-meat and low-vegetable pattern" on MCI. CONCLUSION: In T2DM patients, greater adherence to the "Mediterranean-style dietary pattern" is associated with a lower probability of having MCI. However, excessive consumption of meat, especially red meat and processed meat, combined with a lack of vegetable intake, is associated with a higher probability of having MCI. Greater adherence to the "Western-style dietary pattern" is associated with a higher probability of having MCI. In addition, a pro-inflammatory diet is associated with a higher probability of having MCI, and DII partially mediates the impact of dietary patterns on MCI.

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.

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.

LncRNAS-modulators of neurovascular units in diabetic retinopathy.

As the number of people with diabetes increases, diabetic retinopathy (DR) has become a significant health problem. However, the exact mechanism remains unclear. In recent years, people have tended to think that DR is a neurovascular disease. In the healthy retina, neurons, glial cells, and vascular cells interact with each other to maintain retinal environmental homeostasis and physiological functions. Long noncoding RNAs (lncRNAs) that do not encode proteins regulate various cellular components in the neurovascular unit and are key regulatory molecules involved in processes such as microangiopathy, neurodegeneration, and apoptosis in DR. Here we review the interactions between neurovascular units and the regulation of various cellular components by lncRNAs in an attempt to prove the promise of targeting lncRNAs for the treatment 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.

Association Among Lipid Accumulation Product, Chinese Visceral Obesity Index and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND AND AIM: Obesity often coexists with diabetes, especially abdominal obesity, recognized as a risk factor for diabetic complications. Diabetic retinopathy (DR), as one of the most common microvascular complications of diabetes, may be associated with these indices. Lipid accumulation product (LAP) and Chinese visceral obesity index (CVAI) are novel visceral obesity indicators, which have been proven to be an influential factor predicting type 2 diabetes (T2DM). However, the correlation among LAP, CVAI, and DR still lacks systematic research in T2DM. The study aimed to explore the relationship among LAP, CVAI levels in different DR stages of T2DM patients and the diagnostic efficacy of LAP and CVAI for DR. METHODS: A total of 263 participants were recruited in this cross-sectional study. We enrolled 169 patients with T2DM, divided into the non-DR group (NDR, n = 61), non-proliferative DR group (NPDR, n = 55), and proliferative DR group (PDR, n = 53). And we also enrolled 94 healthy control participants. We collected demographic, anthropometric, and biochemical data on each subject. LAP and CVAI are calculated according to different formulas for men and women. RESULTS: Compared with the control group, LAP and CVAI were significantly higher (P < 0.05). After adjusting for confounding factors, LAP (OR: 1.029, 95CI%: 1.010-1.049, P < 0.05), WC (OR: 1.073, 95CI%: 1.009-1.141, P < 0.05) and CVAI (OR: 1.017, 95CI%: 1.000-1.033, P < 0.05) were all associated with an increased risk of DR. Furthermore, increased LAP (OR: 1.020, 95% CI: 0.100-0.290) is associated with DR severity (P < 0.001). Moreover, the LAP had the most significant area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.728, 95% CI: 0.653-0.804). CONCLUSION: A high LAP is associated with an increased risk of DR in T2DM patients, and the LAP index appears to be a good predictor of DR risk and severity in patients with T2DM, compared with BMI, WC, and CVAI.

RAAS in diabetic retinopathy: mechanisms and therapies

ABSTRACT 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.