Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Cardiovascular Diabetology, Год журнала: 2022, Номер 21(1)

Опубликована: Май 15, 2022

Abstract Background The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along glucose-lowering properties. Therefore, we investigated link between stress hyperglycemia, burden, infarct size cohort of type diabetic presenting AMI treated versus other oral anti-diabetic (OAD) agents. Methods In this multicenter international observational registry, consecutive undergoing percutaneous coronary intervention (PCI) 2018 2021 were enrolled. Based on presence therapy at admission, divided into those receiving (SGLT-I users) OAD agents (non-SGLT2-I users). following markers evaluated different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), neutrophil-to-platelet (NPR), C-reactive protein. Infarct was assessed by echocardiography peak troponin levels. Results study population consisted 583 (with or ST-segment elevation): 98 users 485 non-SGLT-I users. Hyperglycemia admission less prevalent group. Smaller observed compared to non-SGLT2-I On 24 h, indices significantly higher patients, significant increase neutrophil levels h. At multivariable analysis, use predictor reduced (OR 0.457, 95% CI 0.275–0.758, p = 0.002), independently age, creatinine values, glycemia. Conversely, values NSTEMI occurrence independent predictors status. Conclusions Type exhibited smaller agents, glucose-metabolic control. Our findings are generating provide new insights cardioprotective setting artery disease. Trial Registration: Data part ongoing registry: PROTECT. ClinicalTrials.gov Identifier: NCT 05261867.

Язык: Английский

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Empagliflozin Improves Cognitive Impairment in Frail Older Adults With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction

Diabetes Care, Год журнала: 2022, Номер 45(5), С. 1247 - 1251

Опубликована: Март 14, 2022

To assess whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improves cognitive impairment in frail older adults with diabetes and heart failure preserved ejection fraction (HFpEF).We designed a prospective study to physical function consecutive HFpEF, comparing effects of empagliflozin, metformin, insulin.A total 162 HFpEF successfully completed study. Montreal Cognitive Assessment scores at baseline after 1 month were 19.80 ± 3.77 vs. 22.25 3.27 (P < 0.001) group, 19.95 3.81 20.71 3.56 = 0.26) metformin 19.00 3.71 19.1 0.81) insulin group. A multivariable regression analysis confirmed beneficial empagliflozin. Additionally, we observed marked amelioration impairment, assessed by 5-m gait speed test, groups but not group.This is first show significant SGLT2 on HFpEF.

Язык: Английский

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Pharmacotherapy of type 2 diabetes: An update and future directions

Metabolism, Год журнала: 2022, Номер 137, С. 155332 - 155332

Опубликована: Окт. 12, 2022

Язык: Английский

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Nicorandil alleviates cardiac microvascular ferroptosis in diabetic cardiomyopathy: Role of the mitochondria-localized AMPK-Parkin-ACSL4 signaling pathway

Pharmacological Research, Год журнала: 2024, Номер 200, С. 107057 - 107057

Опубликована: Янв. 11, 2024

Mitochondria-associated ferroptosis exacerbates cardiac microvascular dysfunction in diabetic cardiomyopathy (DCM). Nicorandil, an ATP-sensitive K+ channel opener, protects against endothelial dysfunction, mitochondrial and DCM; however, its effects on mitophagy remain unexplored. The present study aimed to assess the beneficial of nicorandil DCM underlying mechanisms. Cardiac perfusion was assessed using a lectin assay, while via mt-Keima transfection transmission electron microscopy. Ferroptosis examined mRNA sequencing, fluorescence staining, western blotting. localization Parkin, ACSL4, AMPK determined immunofluorescence staining. Following long-term diabetes, treatment improved function remodeling by alleviating injuries, as evidenced structural integrity. mRNA-sequencing biochemical analyses showed that occurred Pink1/Parkin-dependent suppressed cells after diabetes. Nicorandil mitochondria-associated promoting mitophagy. Moreover, increased phosphorylation level AMPKα1 promoted translocation, which further inhibited translocation ACSL4 ultimately ferroptosis. Importantly, overexpression mitochondria-localized (mitoAα1) shared similar benefits with mitophagy, cardiovascular protection injury. In conclusion, demonstrated therapeutic revealed AMPK-Parkin-ACSL4 signaling pathway mediates development dysfunction.

Язык: Английский

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Diabetes and restenosis

Cardiovascular Diabetology, Год журнала: 2022, Номер 21(1)

Опубликована: Фев. 14, 2022

Restenosis, defined as the re-narrowing of an arterial lumen after revascularization, represents increasingly important issue in clinical practice. Indeed, number stent placements has risen to estimate that exceeds 3 million annually worldwide, revascularization procedures have become much more common. Several investigators demonstrated vessels patients with diabetes mellitus increased risk restenosis. Here we present a systematic overview effects on in-stent Current classification and updated epidemiology restenosis are discussed, alongside main mechanisms underlying pathophysiology this event. Then, summarize presentation restenosis, emphasizing importance glycemic control diabetic patients. who underwent proper remains imperative.

Язык: Английский

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Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes

Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2022, Номер 384(1), С. 116 - 122

Опубликована: Июль 25, 2022

Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial in these patients are lacking. In this study, we evaluated the expression of panel circulating microRNAs (miRs) involved regulation function frail older adults HFpEF DM that were treated for 3 months empagliflozin, metformin, or insulin. We identified unique pattern miRs significantly regulated compared healthy controls after treatment SGLT2 inhibitor empagliflozin. Three downregulated (miR-126, miR-342-3p, miR-638) two upregulated (miR-21 miR-92) controls. Strikingly, reduced 3-month empagliflozin whereas no significant differences profile miRNAs detected metformin Significance Statement have first time signature microRNA functionally is diabetes. The caused modification some direction was opposite what observed patients, indicating rescue function. Our findings relevant inasmuch as novel disease well response therapy been established.

Язык: Английский

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Hyperglycemia and Physical Impairment in Frail Hypertensive Older Adults

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Апрель 14, 2022

Frailty is a multidimensional condition typical of elders. Frail older adults have high risk functional decline, hospitalization, and mortality. Hypertension one the most common comorbidities in Hyperglycemia (HG) frequently observed frail adults, represents an independent predictor worst outcomes, with or without diabetes mellitus (DM). We aimed at investigating impact HG on physical impairment frailty.We studied consecutive frailty hypertension ASL (local health unit Italian Ministry Health) Avellino, Italy, from March 2021 to September 2021. Exclusion criteria were: age <65 years, no frailty, hypertension, left ventricular ejection fraction <25%, previous myocardial infarction, primary percutaneous coronary intervention and/or artery bypass grafting. Blood glucose, Hb1Ac, creatinine were measured all patients. Physical was assessed applying Fried Criteria; we performed 5-meter gait speed (5mGS) test patients.149 hypertensive enrolled study, which 82 had normoglycemia (NG), 67 HG. significantly slower 5mGS group compared NG (0.52 ± 0.1 vs. 0.69 0.06; p<0.001). Moreover, found strong significant correlation between glycemia (r: 0.833; A multivariable linear regression analysis using as dependent variable revealed association (p<0.001) after adjusting for likely confounders.HG drives independently DM.

Язык: Английский

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L-Arginine in diabetes: clinical and preclinical evidence

Cardiovascular Diabetology, Год журнала: 2023, Номер 22(1)

Опубликована: Апрель 18, 2023

Abstract L-Arginine (L-Arg), is a semi-essential amino acid involved in the formation of nitric oxide. The functional relevance L-Arg diabetes mellitus has been evaluated both animal models and human subjects. In literature there are several lines evidence indicating that beneficial effects numerous studies advocate its administration to attenuate glucose intolerance diabetic patients. Here we present comprehensive overview main exploring diabetes, including preclinical clinical reports on this topic.

Язык: Английский

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Stress Hyperglycemia Drives the Risk of Hospitalization for Chest Pain in Patients With Ischemia and Nonobstructive Coronary Arteries (INOCA)

Diabetes Care, Год журнала: 2022, Номер 46(2), С. 450 - 454

Опубликована: Дек. 7, 2022

OBJECTIVE Ischemia with nonobstructive coronary arteries (INOCA) is a prevailing finding in patients angina. However, the main factors underlying risk of being rehospitalized for chest pain INOCA remain mostly unknown. RESEARCH DESIGN AND METHODS We evaluated referred to “Casa di Cura Montevergine” Mercogliano (Avellino), Italy, from January 2016 2021 percutaneous intervention (PCI). In these subjects, we assessed impact stress hyperglycemia ratio (SHR), defined as mmol/L blood glucose and % HbA1c, on rehospitalization pain. RESULTS A total 2,874 successfully completed study. At 1-year follow-up, was significantly higher (P &lt; 0.001) SHR &gt;1 compared ≤1. These findings were confirmed by multivariable analyses (adjusting potential confounders, including age, BMI, pressure, heart rate, chronic kidney disease, cholesterol), propensity score matching, inverse probability treatment weighting. CONCLUSIONS Our data indicate, our knowledge first time, that hospital admission independently increases patients.

Язык: Английский

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Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart

Hypertension, Год журнала: 2023, Номер 80(9), С. 1800 - 1809

Опубликована: Июль 5, 2023

SGLT2 (sodium-glucose cotransporter 2) enables glucose and sodium reabsorption in the kidney. SGLT2-inhibitors (also known as gliflozins, which include canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) act by increasing glycosuria, thereby reducing glycemia. These drugs are critical to reach keep glycemic control, a crucial feature, especially patients with comorbidities, like frail individuals. Several studies evaluated effects of different settings beyond diabetes, revealing that they actually pleiotropic drugs. We recently evidenced favorable SGLT2-inhibition on physical cognitive impairment older adults diabetes hypertension. In present overview, we summarize latest clinical preclinical exploring main kidney heart, emphasizing their potential beneficial actions frailty.

Язык: Английский

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