View clinical trials related to Metabolic Disorder.
Filter by:Dietary interventions have been consistently proposed as a part of a comprehensive strategy to lower the incidence and severity of atherosclerosis and coronary vascular disease. Excessive comsumption of fats enriched in saturated fatty acids (SFAs) is associated with an increased risk of atherosclerosis and other cardiovascular diseases (CVD). In contrasts, replacement of SFAs with monounsaturated fatty acids (MUFAs) and omega-3 long chain polyunsaturated fatty acids (ω3-LCPUFAs) has been reported to be inversely associated with risk of atherosclerosis. This is partly due to the ability of MUFAs (and ω3-LCPUFAs) to modulate lipoprotein composition, oxidation state, and consequently their functionality, among others. While most of the nutritional studies have focused on elucidating the mechanisms by which dietary fats affect lipoprotein particles, little or nothing is known about the regulatory effect of dietary fatty acids on extracellular vesicles (EVs). EVs are small phospholipid particles that convey molecular bioactive cargoes and play essential roles in intercellular communication and, hence, a multifaceted role in health and disease. For the first time, the purpose of this project is to establish whether the type of major fatty acids present on a diet (SFAs, MUFAs, or ω3-LCPUFAs) may alter the structure, cargo, and functionality of postprandial- and long-term-EVs. In the precision nutrition era, the investigators expect to offer a new insight on EVs and their relationship with dietary fatty acids through the following objectives: 1) To map changes in the lipidome, proteome, microtranscriptome, and functional properties of circulating EVs in healthy subjects and patients with metabolic syndrome (MetS) both at fasting and at postprandial state upon a challenge of a meal rich in SFAs, MUFAs, and ω3-LCPUFAs; 2) To analyse the contribution of postprandial triacylglyceride-rich lipoproteins (TRL) on EVs-mediated intercellular communication in a fatty acid-dependent manner; and 3) To determine the influence of diets rich in SFAs, MUFAs, and ω3-LCPUFAs on EVs in an animal model of atherosclerosis in the setting of MetS. Collectively, this project will provide fundamental insight into EV biology, and remarks the clinical and functional relevance and divergent consequences of dietary fatty acids in health and disease.
Advances in patient selection, organ procurement and preservation, surgical technique, immunosuppression, and infection prevention have conferred significant decrease in rejection, infection, and subsequently improve cause-specific graft failure rates after kidney transplantation (KT). However, cardiovascular diseases (CVD) remained the main burden impairing both short-and long-term survival. Compared with the general population, conventional CVD risk factors, including obesity, liver and muscle insulin resistance, dyslipidemia, hypertension, and diabetes mellitus, are all highly prevalent in this population. Risk factors of these metabolic disorders are generally reported, including common risk factors and those specifically for kidney transplants, including long-term exposure to steroids and calcineurin inhibitors. Previous studies demonstrated that adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and a key player in regulating cellular energy metabolism. Activation of AMPK by pharmacological agents may hold a considerable potential to reverse the metabolic abnormalities in chronic metabolic diseases. Metformin, a widely used antidiabetic drug, have been reported to act as an AMPK activator by inhibiting complex I of the mitochondrial electron transport chain in many tissues, including adipose, skeletal muscle, and heart. A recent small clinical trial observed that metformin administration did improve some of the metabolic profiles for glucocorticoid-treated patients with inflammatory disease but without pre-existing diabetes. In addition, another antidiabetic drug sodium-glucose-cotransporter-2 (SGLT-2) inhibitors can improve metabolic parameters and cardiovascular risk in patients with or without diabetes in preclinical and clinical studies. A small clinical trial reported that compared to metformin, significant improvement in anthropometric parameters and body composition, in overweight and obese women with polycystic ovary syndrome after 12 weeks of treatment with empagliflozin. Hence, metformin and SGLT2 agents may be used as potential adjuvant therapies to improve metabolic disorders after KT. However, both metformin and SGLT-2 inhibitors were not recommended in patients with impaired kidney function considering their elimination and action mechanism. Although several preliminary clinical trials showed that metformin and SGLT-2 inhibitors can be used safely and improve glucose control after KT, but they are small-sample sized and only include patients with diabetes. We will conduct a prospective clinical trial with the first aim of exploring the safety of metformin and SGLT-2 inhibitors in kidney transplant recipients with or without diabetes, and the second aim of exploring their roles in improving metabolic profiling.