key: cord-0867624-obhuzi2t authors: Rizvi, Ali Abbas; Stoian, Anca Pantea; Rizzo, Manfredi title: Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies date: 2021-09-17 journal: Int J Mol Sci DOI: 10.3390/ijms221810038 sha: 191fd1469f56de03b783a5fe4ef4ea1130f5e5ab doc_id: 867624 cord_uid: obhuzi2t The metabolic syndrome (MetS) consists of a cluster of metabolic abnormalities including central obesity, insulin resistance, glucose intolerance, hypertension, and atherogenic dyslipidemia [...]. The metabolic syndrome (MetS) consists of a cluster of metabolic abnormalities including central obesity, insulin resistance, glucose intolerance, hypertension, and atherogenic dyslipidemia [1] ; it is rapidly emerging as a global health problem that increases the risk of developing type 2 diabetes and cardiovascular diseases [2] . An early recognition using clinical parameters and inflammatory markers is imperative in order to reduce morbidity and possibly mortality too, attributable to the syndrome. In addition, a number of susceptibility genes and adipokines have been identified that are thought to play a role in the genetic etiology of MetS, thus paving the way to new molecular insights [3] [4] [5] . Knowledge of the etiopathogenic pathways could facilitate novel therapeutic approaches to managing and treating MetS. The link between MetS and diabetes and its complications, such as cardiovascular diseases, is a newly developing paradigm with the central point being early atherosclerosis and endovascular inflammation, where atherogenic dyslipidemia seems to have a critical role [6] . LDL seems to be pivotal for the formation and progression of atherosclerotic plaques; however, LDL are not homogenous particles, since they differ for many important pro-atherogenic properties, including metabolic behaviour, affinity to the LDL receptor and susceptibility to oxidation [7] . Indeed, small, dense LDL particles are those with stronger atherogenic potential, and recognized as an independent risk factor for cardiovascular diseases [8] . This highlights the clinical importance of both quality and quantity of LDL. Patients at higher cardiovascular risk have elevated concentrations of small, dense LDL [9] [10] [11] [12] [13] , which are strictly linked to the early stages of subclinical atherosclerosis and endothelial dysfunction, both enhancing the risk of cardiovascular events [14] . Of interest, some novel anti-diabetic agents have shown favorable effects in subjects with the MetS [15] due to an improvement of patho-physiological alterations [16, 17] , and increasing evidence is accumulating for incretin-based therapies as effective measure for preventing of cardiometabolic complications [18] . In the last 18 months the MetS has received particular attention, since diabetes, obesity, and hypertension have been shown to be significantly associated with an increased risk for more severe forms of COVID-19 and related deaths [19] . The optimal management to address the multiple components of cardiometabolic risk during COVID-19 is still evolving. It has been suggested that a thoughtful approach to the management of cardiometabolic disorders would reduce inflammation, improve immune response, and prevent deterioration in case of SARS-Cov-2 infection [20] . The data gathered thus far could guide future management of patients with the MetS in order to reduce the risk of developing these complications [21] . This Special Issue aims to provide an update on the latest research in MetS, shedding light on emerging markers, unravelling potential molecular mechanisms, and highlighting innovative remedies to be utilized in concert with lifestyle modifications. We hope that the issue will assist readers in keeping abreast of the health challenges and their emerging solutions in the modern era of the COVID-19 pandemic. Our intention is to gather relevant knowledge under one umbrella as a resource for clinicians and for the benefit of patients with the MetS and its complications. Banting lecture 1988. Role of insulin resistance in human disease The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes American College of Endocrinology position statement on the insulin resistance syndrome Resistin: An inflamma-tory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome Cytokine biomarkers, endothelial inflammation, and atherosclerosis in the metabolic syn-drome: Emerging concepts Metabolic origins and clinical significance of LDL heterogeneity Who needs to care about small, dense low-density lipoproteins? Atherogenic forms of dyslipidemia in women with polycystic ovary syndrome Atherogenic lipoprotein phenotype and LDL size and sub-classes in patients with peripheral arterial disease Athero-genic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes Ethnic differences in serum lipoproteins and their determinants in South African women Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with early rheumatoid arthritis Endothelial dysfunction and carotid le-sions are strong predictors of clinical events in patients with early stages of atherosclerosis: A 24-month follow-up study Liraglutide improves metabolic parameters and carotid inti-ma-media thickness in diabetic patients with the metabolic syndrome: An 18-month prospective study Exenatide once-weekly improves metabolic parameters, endothelial dysfunction and carotid intima-media thickness in patients with type-2 diabe-tes: An 8-month prospective study Lirag-lutide reduces carotid intima-media thickness by reducing small dense low-density lipoproteins in a re-al-world setting of patients with type 2 diabetes: A novel anti-atherogenic effect The Evolving Story of Incretins (GIP and GLP-1) in Metabolic and Cardiovascular Disease: A Pathophysiological Update COVID-19 and diabetes management: What should be considered? COVID-19 editorial: Mechanistic links and therapeutic challenges for metabolic diseases one year into the COVID-19 pandemic Diabetes and the COVID-19 Pandemic: How Insights from Re-cent Experience Might Guide Future Management