scholarly journals Cardiovascular Benefits of GLP-1-BasedTherapies in Patients with Diabetes Mellitus Type 2: Effects on Endothelial and Vascular Dysfunction beyond Glycemic Control

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Thomas Forst ◽  
Matthias M. Weber ◽  
Andreas Pfützner
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vascular Function ◽  
Current Knowledge ◽  
Vascular Dysfunction ◽  
Cardiovascular Effects ◽  
Glucagon Secretion ◽  
Receptor Agonists ◽  
Dpp Iv

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.

scholarly journals The vascular epigenome in patients with obesity and type 2 diabetes: opportunities for personalized therapies

2020 ◽  
Vol 2 (1) ◽  
pp. H19-H28 ◽  
Author(s):  
Sarah Costantino ◽  
Shafeeq A Mohammed ◽  
Samuele Ambrosini ◽  
Francesco Paneni
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Function ◽  
Current Knowledge ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Epigenetic Modifications ◽  
Individual Risk ◽  
Limited Information ◽  
Obesity And Diabetes

Our genetic background provides limited information on individual risk of developing vascular complications overtime. New biological layers, namely epigenetic modifications, are now emerging as potent regulators of gene expression thus leading to altered transcriptional programs and vascular disease phenotypes. Such epigenetic modifications, defined as changes to the genome that do not involve changes in DNA sequence, are generally induced by environmental factors and poor lifestyle habits. Of note, adverse epigenetic signals acquired during life can be transmitted to the offspring thus leading to premature alterations of the epigenetic and transcriptional landscape eventually leading to early endothelial dysfunction and vascular senescence. Modifications of the epigenome play a pivotal role in the pathophysiology of cardiometabolic disturbances such as obesity and type 2 diabetes. In these patients, changes of DNA methylation and chromatin structure contribute to alter pathways regulating insulin sensitivity, glucose homeostasis, adipogenesis and vascular function. In this perspective, unveiling the ‘epigenetic landscape’ in cardiometabolic patients may help to identify new players implicated in obesity and diabetes-related vascular dysfunction and may pave the way for personalized therapies in this setting. In the present review, we discuss current knowledge of the epigenetic routes implicated in vascular damage and cardiovascular disease in patients with metabolic alterations.

scholarly journals Incretin-Based Antidiabetic Agents: A New Option for Type-2 Diabetes Mellitus

1970 ◽  
Vol 6 (1) ◽  
pp. 51-54
Author(s):  
F Ahammad ◽  
MAR Howlader ◽  
RC Barnab ◽  
MY Ali ◽  
S Naher ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Complex Disease ◽  
Vascular Dysfunction ◽  
Glucagon Secretion ◽  
Dipeptidyl Peptidase 4 ◽  
Glucagon Like Peptide 1 ◽  
Microvascular And Macrovascular Complications

Type 2 Diabetes Mellitus (T2DM) is a complex disease with the co-existence of several pathophysiological abnormalities. Both microvascular and macrovascular complications are the main causes of morbidity and mortality, which develops due to endothelial dysfunction. Upregulation of reactive oxygen species, chronic inflammatory and hypercoagulable states are the pathologic basis of vascular dysfunctions in T2DM. To overcome all these abnormalities, different classes of antihyperglycaemic agents have developed. Unfortunately none is able to show satisfactory glycaemic control and to modulate vascular dysfunction. Incretin hormones are secreted from intestine during meal, which enhance insulin secretion and inhibit glucagon secretion from the pancreas. The incretin effect is severely reduced or absent in T2DM. Incretin-based new antidiabetics, both Dipeptidyl Peptidase-4 (DPP-4) inhibitors (Saxagliptin, Sitagliptin, Vildagliptin) and Glucagon Like Peptide-1 (GLP-1) analogs (Exenatide) are now being used globally. They are almost equally effective as conventional antidiabetics like Sulphonylureas (SU), Metformin (MET), Thiazolidinediones (TZD) and insulin when given as monotherapy or combined with SU, MET or TZD as second line agent. Incretin-based agents do not cause hypoglycaemia, produce weight loss in spite of weight gain and do not retain salt or water and almost no gastrointestinal (GIT) symptoms. The agents correct vascular dysfunctions and dyslipidaemia and can be given in elderly and renal impaired patients. DOI: 10.3329/fmcj.v6i1.7412 Faridpur Med. Coll. J. 2011;6(1): 51-54

Abstract #295 GLP-1 Receptor Agonists and Death From Any Cause in Elderly Patients with Type 2 Diabetes Mellitus: A Post-Hoc Analysis

2018 ◽  
Vol 24 ◽  
pp. 80-81
Author(s):  
Konstantinos Toulis ◽  
Krishna Gokhale ◽  
G. Neil Thomas ◽  
Wasim Hanif ◽  
Krishnarajah Nirantharakumar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elderly Patients ◽  
Post Hoc Analysis ◽  
Receptor Agonists ◽  
Post Hoc

Glucagon-like peptide-1 agonist therapy in patients with diabetes mellitus and obesity

2020 ◽  
Vol 98 (3) ◽  
pp. 210-217
Author(s):  
A. Yu. Babenko ◽  
Yu. A. Kononova ◽  
M. V. Martjanova ◽  
A. V. Simanenkova ◽  
M. A. Kokina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Hba1c Level ◽  
High Efficiency ◽  
Receptor Agonists ◽  
Predictors Of Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Lipids Metabolism

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

Effects of three types of bariatric interventions on myocardial infarct size and vascular function in rats with type 2 diabetes mellitus

Life Sciences ◽  
2021 ◽  
pp. 119676
Author(s):  
Oleg V. Kornyushin ◽  
Dmitry L. Sonin ◽  
Alexander S. Polozov ◽  
Vitaly V. Masley ◽  
Maria S. Istomina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Infarct Size ◽  
Vascular Function ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size
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