scholarly journals Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes

2020 ◽  
Vol 9 (4) ◽  
pp. 912 ◽  
Author(s):  
Angelo Maria Patti ◽  
Ali A Rizvi ◽  
Rosaria Vincenza Giglio ◽  
Anca Pantea Stoian ◽  
Daniela Ligi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Subclinical Atherosclerosis ◽  
Macrophage Polarization ◽  
Vascular Complications ◽  
Rapid Progression ◽  
Glucose Lowering ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint.

scholarly journals Impact of Glucose-Lowering Medications on Cardiometabolic Risk in Type 2 Diabetes

2019 ◽  
Author(s):  
Angelo Maria Patti ◽  
Ali A Rizvi ◽  
Rosaria Vincenza Giglio ◽  
Anca Pantea Stoian ◽  
Daniela Ligi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Subclinical Atherosclerosis ◽  
Macrophage Polarization ◽  
Vascular Complications ◽  
Rapid Progression ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

Sulfonylureas in today’s blood glucose lowering therapy.New data on advantages and potential barriers of an “old” antidiabetic group

2015 ◽  
Vol 156 (13) ◽  
pp. 511-515
Author(s):  
Gábor Winkler
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Sulfonylurea Compounds ◽  
Drug Of Choice ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today’s therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs − first of all dipeptidyl peptidase-4 inhibitors − and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect. Orv. Hetil., 2015, 156(13), 511–515.

scholarly journals Molecular mechanisms and the vital roles of resistin, TLR 4, and NF-κB in treating type 2 diabetic complications

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Venkataiah Gudise ◽  
Bimalendu Chowdhury
Keyword(s):  
Type 2 Diabetes ◽  
Effective Treatment ◽  
Diabetic Complications ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Rapid Progression ◽  
Main Body

Abstract Background Type 2 diabetes in obese (≥ 25 and ≥ 30 kg/m2) patients is the foremost cause of cardiovascular complications like stroke, osteoarthritis, cancers (endometrial, breast, ovarian, liver, kidney, colon, and prostate), and vascular complications like diabetic neuropathy, diabetic and retinopathy, and diabetic nephropathy. It is recognized as a global burden disorder with high prevalence in middle-income nations which might lead to a double burden on health care professionals. Hence, this review emphasizes on understanding the complexity and vital signaling tracts involved in diabetic complications for effective treatment. Main body Type 2 diabetes in overweight patients induces the creation of specific ROS that further leads to changes in cellular proliferation, hypothalamus, and fringe. The resistin, TLR4, and NF-κB signalings are mainly involved in the progression of central and fringe changes such as insulin resistance and inflammation in diabetic patients. The overexpression of these signals might lead to the rapid progression of diabetic vascular complications induced by the release of proinflammatory cytokines, chemokines, interleukins, and cyclooxygenase-mediated chemicals. Until now, there has been no curative treatment for diabetes. Therefore, to effectively treat complications of type 2 diabetes, the researchers need to concentrate on the molecular mechanisms and important signaling tracts involved. Conclusion In this review, we suggested the molecular mechanism of STZ-HFD induced type 2 diabetes and the vital roles of resistin, TLR4, and NF-κB signalings in central, fringe changes, and development diabetic complications for its effective treatment. Graphical abstract

scholarly journals Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 233
Author(s):  
Elisabetta Bigagli ◽  
Cristina Luceri ◽  
Ilaria Dicembrini ◽  
Lorenzo Tatti ◽  
Francesca Scavone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Propensity Score ◽  
Oxidative Damage ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

Pre-clinical studies suggested potential cardiovascular benefits of dipeptidyl peptidase-4 inhibitors (DPP4i), however, clinical trials showed neither beneficial nor detrimental effects in patients with type 2 diabetes mellitus (T2DM). We examined the effects of DPP4i on several circulating oxidative stress markers in a cohort of 32 T2DM patients (21 males and 11 post-menopausal females), who were already on routine antidiabetic treatment. Propensity score matching was used to adjust demographic and clinical characteristics between patients who received and who did not receive DPP4i. Whole-blood reactive oxygen species (ROS), plasma advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), carbonyl residues, as well as ferric reducing ability of plasma (FRAP) and leukocyte DNA oxidative damage (Fpg sites), were evaluated. With the exception of Fpg sites, that showed a borderline increase in DPP4i users compared to non-users (p = 0.0507), none of the biomarkers measured was affected by DPP4i treatment. An inverse correlation between estimated glomerular filtration rate and AGEs (p < 0.0001) and Fpg sites (p < 0.05) was also observed. This study does not show any major effect of DPP4i on oxidative stress, assessed by several circulating biomarkers of oxidative damage, in propensity score-matched cohorts of T2DM patients.

scholarly journals Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Samira Tajbakhsh ◽  
Kamelya Aliakbari ◽  
Damian J. Hussey ◽  
Karen M. Lower ◽  
Anthony J. Donato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Sirtuin 1 ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Clinical Complications

Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1per seare not sufficient to prematurely shorten vascular telomeres.

Cardiovascular Outcomes Trials in Type 2 Diabetes Mellitus

Cardiology ◽  
2016 ◽  
Vol 135 (2) ◽  
pp. 108-126
Author(s):  
Karan Kapoor ◽  
Praveen George ◽  
Michael Miller
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Disease Risk ◽  
Macrovascular Disease ◽  
Cardiovascular Outcomes ◽  
Significant Shift ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 Inhibitors

Objectives: To review the spectrum of contemporary cardiovascular outcomes trials (CVOTS) in type 2 diabetes mellitus (T2DM), spanning both the pre- and post-ACCORD eras. Methods: We reviewed a total of 12 CVOTs and delineated the two eras in accordance with the 2008 US Food and Drug Administration (FDA) mandate requiring completion of CVOTs prior the licensing of new glucose-lowering agents. The salient implications regarding macrovascular disease complications were summarized. Results: Five trials in the pre-ACCORD and 7 in the post-ACCORD era were identified. Heterogeneous results pertaining to the degree of glycemic control associated with optimal macrovascular disease risk reduction, as well as the safest pharmacologic means to do so, were observed. Conclusions: The post-ACCORD era is representative of a significant shift in the landscape of CVOTs in T2DM, with an emphasis on safety of glucose-lowering agents. Recently completed and ongoing trials of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors will continue to inform clinical practice on safe and effective ways to reduce CV risk in T2DM.

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