Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin’s efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin’s beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.

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Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00206.2015 ◽

2016 ◽

Vol 310 (2) ◽

pp. H153-H173 ◽

Cited By ~ 41

Author(s):

Rudo F. Mapanga ◽

M. Faadiel Essop

Keyword(s):

Oxidative Stress ◽

Polyol Pathway ◽

Cardiovascular Complications ◽

Hexosamine Biosynthetic Pathway ◽

Kinase C ◽

Glycation End Products ◽

Global Health Problem ◽

Metabolic Cycle ◽

Damaging Effects

The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.

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Different antihyperglycaemic drug effects on glycaemic variability in Type 2 diabetic patients

Diabetes Mellitus ◽

10.14341/dm2014472-80 ◽

2014 ◽

Vol 17 (4) ◽

pp. 72-80 ◽

Cited By ~ 1

Author(s):

Alina Babenko ◽

Elena Ivanovna Krasilnikova ◽

Nikolay Pavlovich Likhonosov ◽

Anna Pavlovna Likhonosova ◽

Elena Nikolaevna Grineva

Keyword(s):

Treatment Strategies ◽

Vascular Complications ◽

Drug Effects ◽

Glycated Haemoglobin ◽

Cardiovascular Complications ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Glycaemic Variability ◽

Beneficial Effects

Optimizing treatments for type 2 diabetes mellitus (T2DM) remains an urgent issue. In addition to T2DM treatment strategies, such as glycaemic goals (glucose and glycated haemoglobin ? HbА1c) among different patient populations, the influence of glycaemic variability (GV) on the prognosis of patients with T2DM is also important. According to recent data, GV is associated with cardiovascular complications arising from T2DM. However, although the influence of GV on the development of vascular complications arising from diabetes and underlying mechanisms has been extensively investigated, few studies have investigated the effects of different glucose-lowering medications on GV, and there are even fewer reviews of this topic. This type of analysis is highly relevant, particularly because new classes of antidiabetic medications with potent glucose-dependent insulinotropic effects have been developed. These include groups of drugs that mimic or enhance incretin activity, such as glucagon-like peptide (GLP)-1 analogues/mimetics and dipeptidyl peptidase (DPP)-4 inhibitors. A glucose-dependent mechanism suggests that these groups of antidiabetic medications have beneficial effects on GV. Thus, the current study focusses on the comparative analysis of drugs based on their incretin effects (GLP-1 analogues/mimetics and DPP-4 inhibitors) and оther antidiabetic medications with regard to GV in the patients with T2DM.

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Escitalopram Ameliorates Cardiomyopathy in Type 2 Diabetic Rats via Modulation of Receptor for Advanced Glycation End Products and Its Downstream Signaling Cascades

Frontiers in Pharmacology ◽

10.3389/fphar.2020.579206 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lamiaa A. Ahmed ◽

Nesma A. Shiha ◽

Amina S. Attia

Keyword(s):

Glycemic Control ◽

Advanced Glycation End Products ◽

Diabetic Rats ◽

Diabetic Patients ◽

Advanced Glycation ◽

Beneficial Effects ◽

Glycation End Products ◽

End Products ◽

Type 2 Diabetic

Type 2 diabetes mellitus (T2DM) has been recognized as a known risk factor for cardiovascular diseases. Additionally, studies have shown the prevalence of depression among people with diabetes. Thus, the current study aimed to investigate the possible beneficial effects of escitalopram, a selective serotonin reuptake inhibitor, on metabolic changes and cardiac complications in type 2 diabetic rats. Diabetes was induced by feeding the rats high fat-high fructose diet (HFFD) for 8 weeks followed by a subdiabetogenic dose of streptozotocin (STZ) (35 mg/kg, i. p.). Treatment with escitalopram (10 mg/kg/day; p. o.) was then initiated for 4 weeks. At the end of the experiment, electrocardiography was performed and blood samples were collected for determination of glycemic and lipid profiles. Animals were then euthanized and heart samples were collected for biochemical and histopathological examinations. Escitalopram alleviated the HFFD/STZ-induced metabolic and cardiac derangements as evident by improvement of oxidative stress, inflammatory, fibrogenic and apoptotic markers in addition to hypertrophy and impaired conduction. These results could be secondary to its beneficial effects on the glycemic control and hence the reduction of receptor for advanced glycation end products content as revealed in the present study. In conclusion, escitalopram could be considered a favorable antidepressant medication in diabetic patients as it seems to positively impact the glycemic control in diabetes in addition to prevention of its associated cardiovascular complications.

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Particularities of Statin Therapy in Diabetic Patients

Revista de Chimie ◽

10.37358/rc.17.4.5538 ◽

2017 ◽

Vol 68 (4) ◽

pp. 720-725

Author(s):

Ana Maria Pelin ◽

Cristian Catalin Gavat ◽

Gabriela Balan ◽

Eugenia Popescu ◽

Costinela Valerica Georgescu

Keyword(s):

Area Under The Curve ◽

Cardiovascular Complications ◽

Lipid Lowering ◽

Diabetic Patients ◽

Lipid Lowering Therapy ◽

Glucose Levels ◽

Blood Glucose Levels ◽

First Choice ◽

Different Types

The purpose of conducted study was to determine which of the different types of statins ensure a better control of biological markers in diabetic patients and which of the lipid molecules studied, could be a first choice of lipid-lowering therapy in people suffering from diabetes. The measurement of blood glucose levels depending on type of statin used, was another target of this research. Dyslipidaemia was a major risk factor for cardiovascular complications in people with diabetes. It was found that atorvastatin was the most effective statin in controlling dyslipidemia in diabetic, because has ensured optimum control of HDL, LDL - cholesterol, triglycerides and glycemic values, effect which was resulted from the particular chemical structure of atorvastatin. Atorvastatin was discovered to be the best predictor in diabetes mellitus type 2 treatment, with a sensitivity about 78% and specificity to 45%., the most highest values compared to Rosuvastatin and Simvastatin. Area Under the Curve (AUC = 0.610; AUC ]0.600).

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Anti-thyroid antibodies as an additional risk factor for endothelial dysfunction in type 2 diabetic patients with subclinical hypothyroidism

Endocrine Abstracts ◽

10.1530/endoabs.41.ep222 ◽

2016 ◽

Author(s):

Lilit Petrosyan

Keyword(s):

Risk Factor ◽

Endothelial Dysfunction ◽

Subclinical Hypothyroidism ◽

Diabetic Patients ◽

Additional Risk Factor ◽

Thyroid Antibodies ◽

Type 2 Diabetic Patients ◽

Additional Risk ◽

Type 2 Diabetic

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Suicidal Erythrocyte Death in Metabolic Syndrome

Antioxidants ◽

10.3390/antiox10020154 ◽

2021 ◽

Vol 10 (2) ◽

pp. 154

Author(s):

Ignazio Restivo ◽

Alessandro Attanzio ◽

Luisa Tesoriere ◽

Mario Allegra

Keyword(s):

Metabolic Syndrome ◽

Cell Death ◽

Endothelial Dysfunction ◽

Cell Membrane ◽

Clinical Evidence ◽

Current Knowledge ◽

Vascular Complications ◽

Cardiovascular Complications ◽

Inflammatory Milieu ◽

Cardiometabolic Factors

Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed.

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