SGLT-2 inhibitors and in-stent restenosis-related events after acute myocardial infarction: an observational study in patients with type 2 diabetes

BMC Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Фев. 24, 2023

No study evaluated the incidence of intra-stent restenosis (ISR)-related events in patients with type 2 diabetes (T2DM) and acute myocardial infarction (AMI) treated or not sodium/glucose cotransporter inhibitors (SGLT2i).We recruited 377 T2DM AMI undergoing percutaneous coronary intervention (PCI). Among them, 177 were SGLT2 before PCI. The primary outcome was major adverse cardiovascular (MACE) defined as cardiac death, re-infarction, heart failure related to ISR. In without ISR, minimal lumen area diameter assessed by CT-angiography at 1-year follow-up.Glycemic control similar SGLT2i-treated never SGLT2i-users. ISR-related MACE higher SGLT2i-users compared patients, an effect independent glycemic status (HR = 0.418, 95% CI 0.241-0.725, P 0.002) observed also subgroup HbA1c < 7% 0.393, 0.157-0.984, 0.027). event, stent patency greater follow-up.SGLT2i treatment is associated a reduced events, independently control.

Язык: Английский

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Immunomodulatory Effects of SGLT2 Inhibitors—Targeting Inflammation and Oxidative Stress in Aging

International Journal of Environmental Research and Public Health, Год журнала: 2023, Номер 20(17), С. 6671 - 6671

Опубликована: Авг. 29, 2023

Given that the increase in aging population has grown into one of largest public health issues, inflammation and oxidative stress, which are closely associated with process, became a focus recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, group drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement renal function cardioprotective effects. It been SGLT2 drug class, an immunomodulatory antioxidative effect, affecting endothelial well metabolic parameters. Therefore, it is not surprising various studies investigated potential mechanisms action inhibitors age-related diseases. The proposed by can achieve their anti-inflammatory include influence on AMPK/SIRT1/PGC-1α signaling, cytokines, NLRP3 inflammasome. effect related to mitochondria signaling pathways transforming growth factor β nuclear erythroid 2-related 2/antioxidant response element. Also, parameters, such uric acid reduction, stimulation ketogenesis, reduction body weight, lipolysis, epicardial fat tissue. Finally, display anti-atherosclerotic modulate inflammatory reactions, potentially resulting function. This narrative review offers complete comprehensive overview possible pathophysiologic involved process development disease. However, order use inhibitor anti-aging therapy, further basic clinical research needed elucidate complex they processes.

Язык: Английский

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The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes

The Lancet Regional Health - Europe, Год журнала: 2023, Номер 31, С. 100666 - 100666

Опубликована: Июнь 12, 2023

A delay in reaching HbA1c targets patients with newly-diagnosed type 2 diabetes (T2D) is associated an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether early introduction glucose-lowering drugs proven benefit on CVD can attenuate this unknown. Using data derived from large Italian clinical registry, i.e. the AMD Annals, we identified 251,339 subjects T2D and without at baseline. Through Cox regressions adjusted for multiple factors, examined association between having mean 7.1 8% or >8%, compared ≤7%, various periods exposure (0–1, 0–2, 0–3 years) development later (mean subsequent follow-up 4.6 ± 2.9 CVD, evaluated composite myocardial infarction, stroke, coronary peripheral revascularization, bypass. We performed analysis overall cohort then splitting population two groups patients: those that introduced sodium-glucose transport protein inhibitors (SGLT-2i) during phase not treated these drugs. Considering whole cohort, both attaining ≤ 7%, showed outcome all three assessed, highest observed > 3 years period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063–1.365). The SGLT-2i 0–1 0–2 eliminated poor glycemic control (p interaction 0.006 0.003, respectively, vs. same degree but drugs). Among newly diagnosed free baseline, first after diagnosis CVD. This no longer evident when are years, suggesting An treatment might thus promote long-lasting proper diagnosis. work was supported, part, by Ministry Health (Ricerca Corrente) IRCCS MultiMedica.

Язык: Английский

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Organ-specific biological clocks: Ageotyping for personalized anti-aging medicine

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102253 - 102253

Опубликована: Март 4, 2024

Aging is a complex multidimensional, progressive remodeling process affecting multiple organ systems. While many studies have focused on studying aging across organs, assessment of the contribution individual organs to overall processes cutting-edge issue. An organ's biological age might influence other revealing multiorgan network. Recent data demonstrated similar yet asynchronous inter-organs and inter-individuals progression aging, thereby providing foundation track sources declining health in old age. The integration omics with common clinical parameters through artificial intelligence has allowed building organ-specific clocks, which can predict development specific age-related diseases at high resolution. peculiar aging-trajectory, referred as ageotype, provide novel tool for personalized anti-aging, preventive medicine. Here, we review relative clocks omics-based data, suggesting different rates. Additional research longitudinal including young subjects analyzing sex-related differences, should be encouraged apply ageotyping analysis purposes practice.

Язык: Английский

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Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement

Current Problems in Cardiology, Год журнала: 2024, Номер 49(5), С. 102524 - 102524

Опубликована: Март 16, 2024

Язык: Английский

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Heart Failure With Preserved Ejection Fraction in the Elderly Population: Basic Mechanisms and Clinical Considerations

Canadian Journal of Cardiology, Год журнала: 2024, Номер 40(8), С. 1424 - 1444

Опубликована: Апрель 10, 2024

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Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical evidence to molecular mechanisms

Pharmacological Research, Год журнала: 2023, Номер 188, С. 106667 - 106667

Опубликована: Янв. 16, 2023

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are effective, well-tolerated, and safe glucose-lowering compounds for patients with type 2 diabetes mellitus (T2DM). SGLT2i benefit encompasses protection from heart kidney failure, independently of the presence diabetes. In addition, consistently reduce risk hospitalization failure and, although some heterogeneity between specific members class, favourably affect cardiovascular outcomes. The molecular mechanisms underlying favourable effect not fully clarified. Studies testing efficacy in human cohorts experimental models atherosclerotic disease (ASCVD) have reported significant differences circulating levels composition lipoprotein classes. randomized clinical trials, small but increases low-density cholesterol (LDL-C) been observed, a still undefined significance; on other hand, (although modest) effects high-density (HDL-C) triglycerides reported. At level, glycosuria may promote starving-like state that ultimately leads to metabolic improvement through mobilization fatty acids adipose tissue their oxidation production ketone bodies. This, however, also fuel hepatic synthesis, thus inhibiting atherogenic uptake liver. Long-term studies collecting detailed information lipid-lowering therapies at baseline during trials SGLT2i, as well regularly monitoring lipid profiles warranted disentangle potential implications modulating lipoprotein-mediated risk.

Язык: Английский

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Empagliflozin protects against heart failure with preserved ejection fraction partly by inhibiting the senescence-associated STAT1–STING axis

Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)

Опубликована: Июль 23, 2024

Abstract Heart failure with preserved ejection fraction (HFpEF) is a mortal clinical syndrome without effective therapies. Empagliflozin (EMPA) improves cardiovascular outcomes in HFpEF patients, but the underlying mechanism remains elusive. Here, mice were fed high-fat diet (HFD) supplemented L-NAME for 12 weeks and subsequently intraperitoneally injected EMPA another 4 weeks. A 4D-DIA proteomic assay was performed to detect protein changes failing hearts. We identified 310 differentially expressed proteins (DEPs) (ctrl vs. group) 173 DEPs (HFpEF group). The regulation of immune system processes enriched all groups interferon response genes (STAT1, Ifit1, Ifi35 Ifi47) upregulated downregulated after administration. In addition, treatment suppressed increase levels aging markers (p16 p21) Further bioinformatics analysis verified STAT1 as hub transcription factor during pathological mice. next treated H9C2 cells IFN-γ, primary agonist phosphorylation, investigate whether plays beneficial role by blocking activation. Our results showed that IFN-γ caused cardiomyocyte senescence activation, which inhibited Notably, inhibition significantly reduced cellular possibly regulating STING expression. findings revealed mitigates cardiac inflammation inhibiting STAT1–STING axis may act pivotal pathogenesis HFpEF, especially under inflammatory conditions. Graphical abstract schematic figure depicts model (this drawn using FigDraw software).

Язык: Английский

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Impact of gliflozins on cardiac remodeling in patients with type 2 diabetes mellitus & reduced ejection fraction heart failure: A pilot prospective study. GLISCAR study

Diabetes Research and Clinical Practice, Год журнала: 2023, Номер 200, С. 110686 - 110686

Опубликована: Апрель 25, 2023

Язык: Английский

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SGLT-2 inhibitors as novel treatments of multiple organ fibrosis

Heliyon, Год журнала: 2024, Номер 10(8), С. e29486 - e29486

Опубликована: Апрель 1, 2024

Fibrosis, a significant health issue linked to chronic inflammatory diseases, affects various organs and can lead serious damage loss of function. Despite the availability some treatments, their limitations necessitate development new therapeutic options. Sodium-glucose cotransporter 2 inhibitors (SGLT2i), known for glucose-lowering ability, have shown promise in offering protective effects against fibrosis multiple through glucose-independent mechanisms. This review explores anti-fibrotic potential SGLT2i across different tissues, providing insights into underlying mechanisms highlighting recent research advancements. The evidence positions as future treatments fibrotic diseases.

Язык: Английский

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