The present study aimed to investigate the effect of metformin on diabetes-accelerated atherosclerosis and whether Nod-like receptor protein 3 (NLRP3) inflammasome is a target for metformin. ApoE^-/- male mice were divided randomly into control, streptozocin-induced diabetes mellitus and metformin groups. Metabolic parameters, atherosclerotic lesion, activation of NLRP3 inflammasomes and related signaling pathways were detected. THP-1-differentiated macrophages were used in in vitro experiments. Compared with control mice, increased plasma lipids and proinflammatory interleukin-1β, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein. Treatment with metformin alleviated diabetes-induced metabolic disorders and atherosclerosis, as well as NLRP3 inflammasomes activation and dysregulation of thioredoxin-1/thioredoxin-interacting protein. In vitro experiments showed that high glucose induced the accumulation of reactive oxygen species and activated NLRP3 inflammasomes, which was significantly suppressed by treatment with metformin or antioxidant N-acetyl-L-cysteine. Moreover, Compound C, an inhibitor of adenosine 5'-monophosphate-activated protein kinase (AMPK), blocked the anti-inflammatory effect of metformin, indicating that metformin inhibited high glucose-induced NLRP3 inflammasomes activation through AMPK activation. Moreover, high glucose decreased thioredoxin-1 expression and increased thioredoxin-interacting protein expression, which was also reversed by metformin. Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes-accelerated atherosclerosis in apoE^-/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1/thioredoxin-interacting protein.

Aims. To investigate the distribution of diabetic retinopathy (DR) by sex in patients with type 2 diabetes mellitus (T2DM) in a twelve-province cross-sectional study in China. Methods. Patients with T2DM, whose ages were ≥18 years, were recruited from 76 cities/counties in 12 provinces in mainland China between January 2015 and December 2018. All participants received a standardized interview, eye examinations, and digital fundus photography. The presence and severity of DR were diagnosed and classified by retina specialists according to the DR domestic typing method. Results. A total of 12,766 participants (5963 males and 6803 females) were eligible for this study. The total prevalence of DR was 30.1%. Females exhibited a significantly higher prevalence of DR than males (31.1% vs. 29.0%, P=0.011). A multivariate logistic regression analysis confirmed that female sex was an independent predictor for a higher prevalence of DR after adjusting for age, the duration of diabetes, economic status, and the presence of hypertension (OR: 1.096, 95% CI: 1.013-1.186, P=0.023). Even after stratification by the diabetic duration, age, and economic status, female sex was still independently associated with the presence of DR in patients whose T2DM history was more than 10 years, whose ages were over 60 years, or who were in a relatively intermediate economic area. Conclusion. Females had a higher prevalence of DR than males in T2DM patients with a diabetic history of more than 10 years, ages over 60 years, or a relatively intermediate economic status.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Background: Chronic inflammation in type 2 diabetes mellitus (T2DM) is an essential contributor to the development of diabetic retinopathy (DR). The monocyte–to–high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is a novel and simple measure related to inflammatory and oxidative stress status. However, little is known regarding the role of the MHR in evaluating the development of DR.Methods: A total of 771 patients with T2DM and 607 healthy controls were enrolled in this cross-sectional study. MHR determination and eye examination were performed. The association of MHR with the prevalence of DR in T2DM patients was analyzed.Results: The MHR in patients with DR was significantly higher than that in both non-DR diabetic patients (P < 0.05) and healthy controls (P < 0.01). No significance was observed in the MHR of different DR severity grades. Moreover, the MHR was similar between patients with non-macular oedema and those with macular oedema. Logistic regression analysis demonstrated that MHR was independently associated with the prevalence of DR in diabetic patients [odds ratio (OR) = 1.438, 95% confidence interval (CI): 1.249–1.655, P < 0.01]. After additional stratification by HbA1c level and diabetic duration, the MHR was still independently associated with the prevalence of DR.Conclusions: Our study suggests that the MHR can be used as a marker to indicate the prevalence of DR in patients with T2DM.

Early diagnosis of acute ST-segment elevation myocardial infarction (STEMI) and early determination of the culprit vessel are associated with a better clinical outcome. We developed three deep learning (DL) models for detecting STEMIs and culprit vessels based on 12-lead electrocardiography (ECG) and compared them with conclusions of experienced doctors, including cardiologists, emergency physicians, and internists. After screening the coronary angiography (CAG) results, 883 cases (506 control and 377 STEMI) from internal and external datasets were enrolled for testing DL models. Convolutional neural network-long short-term memory (CNN-LSTM) (AUC: 0.99) performed better than CNN, LSTM, and doctors in detecting STEMI. Deep learning models (AUC: 0.96) performed similarly to experienced cardiologists and emergency physicians in discriminating the left anterior descending (LAD) artery. Regarding distinguishing RCA from LCX, DL models were comparable to doctors (AUC: 0.81). In summary, we developed ECG-based DL diagnosis systems to detect STEMI and predict culprit vessel occlusion, thus enhancing the accuracy and effectiveness of STEMI diagnosis.