The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Sept. 2, 2023

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy ultimately increases the mortality of diabetic patients. Endothelial dysfunction, has been recognized as key factor in pathogenesis macroangiopathy, reduction NO bioavailability. Oxidative stress, main pathogenic diabetes, one major triggers endothelial dysfunction through NO. In this review, we summarize four sources ROS vasculature underlying molecular mechanisms factors hyperlipidaemia, adipokines insulin resistance induce oxidative stress cells context diabetes. addition, discuss stress-targeted interventions, including hypoglycaemic drugs, antioxidants lifestyle their effects on diabetes-induced dysfunction. summary, our review provides comprehensive insight into roles

Language: Английский

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Risk of diabetic retinopathy and diabetic macular oedema with sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database

Diabetologia, Journal Year: 2024, Volume and Issue: 67(7), P. 1271 - 1282

Published: April 8, 2024

Abstract Aims/hypothesis A protective role of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development diabetic retinopathy macular oedema has been described some recent studies, which may extend beyond glycaemic control. We aimed to review clinical impact SGLT2i GLP1-ra therapy on risk individuals with type diabetes taking insulin. Methods This is a retrospective cohort analysis approximately two million people receiving insulin across 97 healthcare organisations using global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n =176,409; =207,034) were compared against control (insulin no SGLT2i/GLP1-ra, =1,922,312). Kaplan–Meier survival was performed estimated HRs reported for each outcome. Propensity score used 1:1 match age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney HbA 1c , BMI use pioglitazone, lipid modifying agents, antilipemic ACE inhibitors, angiotensin II metformin. sub-analysis comparing also performed. Results associated reduced HR (95% CI) (0.835; 0.780, 0.893), while demonstrated lack signal statistical significance (1.013; 0.960, 1.069). not clinically significant increase developing (1.076; 1.027, 1.127), increased (1.308; 1.261, 1.357). Compared higher (1.205; 1.153, 1.259) (1.130; 1.056, 1.208). Conclusions/interpretation Our study suggests that combination lower oedema. However, an comparative showed favourable outcomes retinopathy. RCTs dedicated retinal imaging are required determine causal relationship these therapies. Graphical

Language: Английский

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New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15160 - 15160

Published: Oct. 13, 2023

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals metabolites in circulatory system. The senescence death ECs not only adverse outcomes, but also causal contributors endothelial dysfunction, an early risk marker atherosclerosis. pathophysiological process EC involves both structural functional changes has been linked various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, aberrant metabolite sensing signaling. Multiple forms have documented atherosclerosis, autophagic death, apoptosis, pyroptosis, NETosis, necroptosis, ferroptosis. Despite this, molecular mechanisms underlying or atherogenesis fully understood. To provide a comprehensive update on subject, this review examines historic latest findings alterations associated with different stages

Language: Английский

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Current Treatments for Diabetic Macular Edema

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9591 - 9591

Published: May 31, 2023

Diabetic retinopathy is a major retinal disorder and leading cause of blindness. macular edema (DME) an ocular complication in patients with diabetes, it can impair vision significantly. DME the neurovascular system, causes obstructions capillaries, damage blood vessels, hyperpermeability due to expression action vascular endothelial growth factor (VEGF). These changes result hemorrhages leakages serous components that failures units (NVUs). Persistent retina around macula neural cells constitute NVUs resulting diabetic neuropathy reduction quality. The NVU disorders be monitored by optical coherence tomography (OCT). Neuronal cell death axonal degeneration are irreversible, their development permanent visual loss. Treating before these detected OCT images necessary for neuroprotection maintenance good vision. This review describes effective treatments therefore neuroprotective.

Language: Английский

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Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

Diabetes & Metabolism Journal, Journal Year: 2023, Volume and Issue: 47(3), P. 394 - 404

Published: March 6, 2023

Background: To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.Methods: This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database Taiwan. Totally, 33,021 with type 2 diabetes mellitus using SGLT2is GLP1-RAs 2016 2019 were identified. 3,249 excluded due to missing demographics, age <40 years, prior use any drug, diagnosis retinal disorders, history receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or follow-up data. Baseline characteristics balanced inverse probability treatment weighting propensity scores. DR diagnoses interventions served as primary outcomes. Occurrence proliferative regarded vision-threatening DR.Results: There 21,491 SGLT2i 1,887 GLP1-RA users for analysis. Patients GLP-1 RAs exhibited comparable rate (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 1.03), whereas (SHR, 0.53; CI, 0.42 0.68) was significantly lower group. Also, showed reduced composite surgical outcome 0.58; 0.48 0.70).Conclusion: Compared GLP1-RAs, had interventions, although groups. Thus, may be associated but not development.

Language: Английский

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Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010403 - e010403

Published: Jan. 1, 2025

Tumor cells can drive the senescence of effector T by unbalancing their lipid metabolism, thereby limiting adoptive cell therapy and contributing to tumor immune evasion. Our objective is provide a feasible strategy for enhancing treatment efficacy against solid tumors. In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was anchored onto surface via bioorthogonal reactions, aiming specifically inhibit group IVA cytosolic phospholipase A2α (cPLA2α), key enzyme facilitating phospholipid metabolism senescent state cells. The engineering exerted rare side effects on activation migration cells, but local sustained extravasation ATK downregulated cPLA2α expression, reprogrammed inhibited droplet accumulation. This endows with delayed declined apoptosis maintain tumor-killing potency. Systemic administration surface-engineered resulted in superior infiltration tumors improved antitumor secretion cytotoxic molecules, prolonging survival mice bearing colorectal carcinoma melanoma xenografts. Lipid-metabolically remodeled increase microenvironment, highlighting novel immunotherapy.

Language: Английский

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Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(10), P. 5634 - 5634

Published: May 18, 2022

Sodium-glucose co-transporter 2 inhibitors, also known as gliflozins, were developed a novel class of anti-diabetic agents that promote glycosuria through the prevention glucose reabsorption in proximal tubule by sodium-glucose 2. Beyond regulation homeostasis, they resulted being effective different clinical trials patients with heart failure, showing strong cardio-renal protective effect diabetic, but non-diabetic patients, which highlights possible existence other mechanisms gliflozins could be exerting their action. So far, have been approved for therapeutic use T2DM, and diabetic kidney disease countries, all them diseases common deregulation inflammatory process associated pathology, perpetuates worsens disease. This has observed many diseases, led scientific community to growing interest understanding biological processes lead or control inflammation order able identify potential targets revert this situation contribute amelioration In line, recent studies showed act an anti-inflammatory drug, proposed useful strategy treat linked addition such diabetes, obesity, atherosclerosis, non-alcoholic fatty liver work, we will review regarding role main inhibitors inflammation.

Language: Английский

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Metabolomics of various samples advancing biomarker discovery and pathogenesis elucidation for diabetic retinopathy

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 27, 2022

Diabetic retinopathy (DR) is a universal microvascular complication of diabetes mellitus (DM), which the main reason for global sight damage/loss in middle-aged and/or older people. Current clinical analyses, like hemoglobin A1c, possess some importance as prognostic indicators DR severity, but no effective circulating biomarkers are used clinic currently, and studies on latent pathophysiology remain lacking. Recent developments omics, especially metabolomics, continue to disclose novel potential several fields, including not limited DR. Therefore, based overview we reviewed progress analytical technology prominent roles current status DR, update various DR-related samples via tear well vitreous humor, aqueous retina, plasma, serum, cerebrospinal fluid, urine, feces. In this review, underscored in-depth analysis elucidation common different biological integrated results, namely, alanine, lactate, glutamine. Alanine may participate regulate glucose metabolism through stimulating N-methyl-D-aspartate receptors subsequently suppressing insulin secretion, pathogenesis Abnormal lactate could cause extensive oxidative stress neuroinflammation, eventually leading retinal hypoxia metabolic dysfunction; other hand, high-level damage structure function endothelial cell barrier G protein-coupled receptor 81. glutamine indicates disturbance glutamate recycling, affect activation Müller cells proliferation PPP1CA–YAP–GS–Gln–mTORC1 pathway.

Language: Английский

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Sodium glucose co-transporter 2 (SGLT2) inhibition via dapagliflozin improves diabetic kidney disease (DKD) over time associatied with increasing effect on the gut microbiota in db/db mice

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 26, 2023

Background The intestinal microbiota disorder gradually aggravates during the progression of diabetes. Dapagliflozin (DAPA) can improve diabetes and diabetic kidney disease(DKD). However, whether gut plays a role in protection DAPA for DKD remains unclear. Methods To investigate effects on composition disease progression, our study, we performed 16S rRNA gene sequencing fecal samples from db/m mice (control group), db/db (DKD model those treated with (treat group) at three timepoints 14weeks\18weeks\22weeks. Results We found that remarkably prevented weight loss lowered fasting blood glucose eventually delaying DKD. Intriguingly, study strongly suggested there is aggravated dysbacteriosis increased bile acid development More importantly, comparisons relative abundance phylum level partial least squares-discriminant analysis (PLS-DA) plots roughly reflected effect modulating flora time. Specifically, dominant Firmicutes Bacteroidetes was not meaningfully changed among groups 14 weeks as previous studies described. Interestingly, they were altered treat group compared to more protracted intervention 18 22 weeks. Furthermore, decrease Lactobacillus increase norank_f:Muribaculaceae could account differences observed between Conclusion firstly protective may be related dynamic improvement over time, possibly associated impact pool its antioxidation effect.

Language: Английский

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Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes

JAMA Network Open, Journal Year: 2023, Volume and Issue: 6(12), P. e2348431 - e2348431

Published: Dec. 20, 2023

Importance Diabetic nephropathy and diabetic retinopathy share many similarities in pathophysiological processes. Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) a protective role the risk of retinopathy. Objective To compare sight-threatening associated with SGLT2is other second-line glucose-lowering medications (including pioglitazone, sulfonylureas, dipeptidyl peptidase-4 [DPP-4is]) patients type diabetes (T2D). Design, Setting, Participants This cohort study Taiwan applied new-user active-comparator design. Patient demographic clinical data were obtained from National Health Insurance Research Database. Adult newly diagnosed T2D January 1, 2009, to December 31, 2019, recruited followed up until 2020. Propensity score matching was used identify pairs treated SGLT2i vs DPP-4i, sulfonylurea 2016, 2019. Data analyzed between August 18, 2022, May 5, 2023. Exposures Treatment SGLT2i, sulfonylureas starting on 2016. Main Outcomes Measures The main outcome participants. Cox proportional hazards regression models assess relative matched case control groups. Results A total 3 544 383 identified. After 1:1 propensity matching, 65 930 93 760 42 121 These included 236 574 males (58.6%), mean (SD) age 56.9 (11.8) years. In cohorts, had significantly lower than DPP-4i (adjusted hazard ratio [AHR], 0.57; 95% CI, 0.51-0.63), pioglitazone (AHR, 0.75; 0.69-0.81), 0.62; 0.53-0.71). Kaplan-Meier curves showed cumulative incidence (3.52 6.13; P &amp;lt; .001), (4.32 5.76; (2.94 4.67; .001). Conclusions Relevance found compared sulfonylureas. finding suggests may play not only reduced but also slow progression T2D.

Language: Английский

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