1,720,985 research outputs found
The Emerging Role of Dual GLP-1 and GIP Receptor Agonists in Glycemic Management and Cardiovascular Risk Reduction
Full text linkThe incretin pathway is a self-regulating feedback system connecting the gut with the brain, pancreas, and liver. Its predominant action is on the postprandial glucose levels, with extraglycemic effects on fat metabolism and endovascular function. Of the two main incretin hormones released with food ingestion, the actions of glucagon-like peptide-1 (GLP-1) have been exploited for therapeutic benefit. However, little attention has been paid to glucose-dependent insulinotropic polypeptide (GIP) until the recent experimental introduction of dual agonists, or "twincretins". Interestingly, simultaneous activation of both receptors is not only replicative of normal physiology, it seems to be an innovative way to enhance their mutual salubrious actions. In patients with type 2 diabetes, dual agonists can have powerful benefits for glucose control and weight reduction. Additionally, there is mounting evidence of their favorable cardiovascular impact, making them potentially appealing pharmacologic agents of choice in the future. Although we seem to be poised on the horizons of exciting new breakthroughs, much knowledge has yet to be gained before these novel agents are ready for prime time
Age-Related Changes in Insulin Resistance and Muscle Mass: Clinical Implications in Obese Older Adults
Full text linkThe older segment of the global population is increasing at a rapid pace. Advancements in public health and modern medicine lengthened life expectancy and reduced the burden of disease in communities worldwide. Concurrent with this demographic change is the rise in overweight people and obesity, which is evident in all age groups. There is also an aging-related reduction in muscle mass and function, or sarcopenia, that is exacerbated by sedentary lifestyle and poor nutrition. The coexistence of muscle loss and elevated body mass index, termed “sarcopenic obesity”, has particularly deleterious consequences in older individuals. Worsening insulin resistance and a proinflammatory state operate at the pathophysiologic level and lead to adverse health outcomes such as a proclivity to cardiovascular disease, type 2 diabetes, and even cognitive dysfunction. Although the concept of sarcopenic obesity as a disease construct is being increasingly recognized, a clearer understanding is warranted in order to define its components and health impact. Research is needed at the molecular-cellular level to tie together derangements in insulin action, cytokines, myokines, and endothelial dysfunction with clinical outcomes. Lifestyle modifications as well as targeted nonpharmacologic approaches, such as supplements and antioxidants, appear to have a promising role in reducing the chronic burden of this emerging disorder. Breakthroughs in drug therapies that retard or even reverse the underlying dynamics of sarcopenia and obesity in older persons are being actively explored
New Advances in Metabolic Syndrome
Full text linkIt is with great anticipation and pride that we present a Special Issue entitled “New Advances in Metabolic Syndrome”, which provides a compendium of high-quality original papers written on novel aspects of metabolic syndrome (MetS) [...
Diabetes and COVID-19: What 2 Years of the Pandemic Has Taught Us
No full textAs the world enters its third year of the COVID-19 pandemic, individuals with diabetes have faced particular challenges from the virus. A deleterious bidirectional relationship exists between the two disorders, with heightened inflammatory, immunologic, and cellular mechanisms leading to a more severe illness and increased morbidity and mortality. Tight glucose control, though necessary, is hampered by physical restrictions and difficulty accessing health care. Novel glucose-lowering medications may provide unique benefits in this regard. It is imperative that multi-pronged efforts be prioritized in order to reduce adverse outcomes in patients with diabetes at risk for COVID-19
Cardiovascular outcomes trials with incretin-based medications: a critical review of data available on GLP-1 receptor agonists and DPP-4 inhibitors
No full textGlucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called "incretin-based therapies" (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clinical practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored. A summary of the main findings from CVOTs performed to-date with particular emphasis on various outcomes and inconsistencies observed in the trials is provided. Overall, available data is favourable to the early deployment of GLP-1RAs in clinical practice, fully in line with recommendations from international scientific guidelines, and based on their effects on glucose metabolism parameters, body weight reduction and CV outcomes. Evidence further suggest that the CV benefits of GLP-1RAs may not be a class effect, with GLP-1 analogues having a greater benefit rather than exendin-based agents. (C) 2020 Elsevier Inc. All rights reserved
The efficacy and safety of dipeptidyl peptidase-4 inhibitors compared to other oral glucose-lowering medications in the treatment of type 2 diabetes
Full text linkIntroduction: The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based-medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents.Objective: This review discusses data concerning the use of DPP-4is and their cardiovascular profile, and gives an updated comparison with the other oral glucose-lowering medications with regards to safety and efficacy. Currently available original studies, abstracts, reviews articles, systematic reviews and meta-analyses were included in the review.Discussion: DPP4is are moderately efficient in decreasing the HbA1c by an average of 0.5% as monotherapy, and 1.0% in combination therapy with other drugs. They have a good tolerability and safety profile compared to other glucose-lowering drugs. However, there are possible risks pertaining to acute pancreatitis and pancreatic cancer.Conclusion: Cardiovascular outcome trials thus far have proven the cardiovascular safety for ischemic events in patients treated with sitagliptin, saxagliptin, alogliptin, linagliptin and vildagliptin. Data showing increased rate of hospitalisation in the case of saxagliptin did not seem to be a class effect. (C) 2020 Published by Elsevier Inc
Safety and benefit of incretin-based therapies in patients with type 2 diabetes: learnings and reflections
Full text linkCurrent and emerging drugs for the treatment of atherosclerosis: the evidence to date
No full textIntroduction: Atherosclerosis can be considered a chronic inflammatory process that stands out as a dominant cause of cardiovascular disease (CVD). Since blood lipids are the leading risk factor for atherosclerosis development, lowering low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins reduces the risk of future cardiovascular events. However, there has been significant progress in developing lipid-lowering drugs for aggressive management of dyslipidemia, the rates of CVD events remain unacceptably high, so there is great need to identify novel therapeutic pathways targeting the atherosclerosis process.Areas covered: We discussed the current guidelines on CVD prevention, the role of novel lipid-lowering drugs, as well as emerging drugs for atherosclerosis, emphasizing the current data on compounds targeting inflammatory and oxidant pathways.Expert Opinion: Although novel lipid-lowering drugs all showed their therapeutic efficacy in LDL-C lowering, data regarding their impact on cardiovascular outcomes is still inconclusive. On the other hand, some of the agents targeting inflammatory pathways, especially colchicine, showed promising results in terms of reducing CVD events. In contrast, those pointed at oxidant pathways failed to do so. Finally, exploring ways of targeting new therapeutic venues, such as adaptive immunity and clonal hematopoiesis, is a goal in the future
Genetic and Epigenetic Biomarkers For Diagnosis, Prognosis and Treatment Of Metabolic Syndrome
No full textBackground: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering the precision medicine, it would be advisable to valuate the individual cardio-metabolic risk by estimating the coesistence of risk factors (abdominal obesity, low level of High- Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality.
Objective: To identify genetic and epigenetic biomarkers may assist in the possibility of helping follow-up strategies and other measures of prevention, and in metabolic risk.
Methods: We searched for studies which valued the combination between epigenetic biomarkers and all factors of cardio-metabolic risk.
Results: Numerous researches have investigated the molecular start of metabolic alterations, focusing on the epigenetic mark, as methylation of DNA, histone modifications and non.coding RNAs. It has been found that DNA methylation is the most searched epigenetic sign in the human genome concerning the control of gene expression.
Conclusion: For the screening, diagnosis, and prognosis of metabolic syndrome and the prescription of personalized medicine, the DNA methylation biomarkers specify for subjects have been recognized as an ensuring tool. While these results are promising, further investigations are needed to unravel the complicated synergic association of the genome, epigenome and the situations related to metabolic pathology
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