Active clinical trials for "Insulin Resistance"

Accumulation of intramyocellular lipids (IMCLs) due to increased supply of fatty acids can induce defects in the insulin signaling cascade, causing skeletal muscle insulin resistance. However, the causes for muscle insulin resistance are not well understood. The association of elevated IMCLs and insulin resistance has been shown in obese humans and individuals with type 2 diabetes as well as several animal models of insulin resistance. Despite the strong relationship between IMCLs and insulin resistance, this suggested relationship disappears when well-trained endurance athletes are included into this consideration as this group is highly insulin sensitive. This metabolic enigma has been termed the 'athlete's paradox'. The aim of this project is to resolve the mechanisms contributing to the athlete's paradox.

The growing population of adolescents with insulin resistance (IR) is predicted to create a large public health burden in the next few decades. This study examines the function of brain blood vessels and cognitive function, to test if increasing severity of IR in adolescents is related to reduced cognitive function and reduced brain blood vessel function. Findings from this study may help create treatments to delay or prevent some of the negative effects of IR on cognitive and vascular health.

It will be evaluated whether carnitine, a dietary supplement, reduces liver fat and improves metabolism in individuals who have a high concentration of fat within their liver. Participants will be given either Carnitine or placebo, together with a meal replacement milkshake twice daily for 6 months.

Type 2 diabetes are characterized by insulin resistance in skeletal muscle. Insulin resistance plays a major role for the increased risk of heart disease seen in type 2 diabetes. No specific treatment of insulin resistance is currently available, except from increased physical activity and weight-loss. Insulin resistance is characterized by abnormalities in the use of glucose and fat in the muscle, and is associated with abnormal function and content of mitochondria (the power houses of our cells) as well as increased levels of fat within the muscle. The investigators believe that abnormalities in the use of glucose and fat in muscle cells in response to insulin and exercise can explain why insulin resistance is associated with abnormal function and content of mitochondria and an increased amount of fat in skeletal muscle of patients with type 2 diabetes and individuals with obesity. The major purpose of our project is, therefore, to investigate the effect of insulin in physiological concentrations and the effect of both acute exercise and 8 weeks of high intensity interval exercise-training on insulin sensitivity, body composition, cardiorespiratory fitness and energy metabolism, insulin signaling, mitochondrial dynamics and mitophagy in skeletal muscle 4) regulators of storage of fat into lipid droplets and their interaction with mitochondria in skeletal muscle 5) acetylation and phosphorylation of enzymes (proteins) in major metabolic and signaling pathways, as well as 6) transcriptional and signalling networks regulating mitochondrial biogenesis and substrate metabolism. The effects of insulin in physiological concentrations and a novel exercise-intervention combining biking and rowing will be studied in a comprehensive study of obese patients with type 2 diabetes compared with weight-matched obese and lean healthy controls. The effects of insulin before and after 8 weeks HIIT on whole-body metabolism will be evaluated by measurement of maximal oxygen consumption, and well-known methods to determine insulin-stimulated glucose utilization, insulin secretion and use of glucose and fat. Skeletal muscle and fat tissue samples obtained under these conditions will be used for assessment of tissue-levels of specific sets of genes and enzymes known to be involved in insulin action, quality and size of mitochondria, and storage of fat into lipid droplets and their interaction with mitochondria. This project is expected to provide important and novel insight into the causal relationship between insulin resistance, accumulation of fat and abnormal content and function of mitochondria in skeletal muscle in type 2 diabetes. The investigators ultimately expect that our findings will help us to identify novel molecules or enzymatic pathways, which can be used to develop drugs that can enhance or mimic the effects of insulin and exercise, and hence be used in the prevention and treatment of type 2 diabetes and heart disease.

Fetuin-A has been identified as a novel physiological regulator of insulin action in vitro, in intact cells and in vivo in animals. Previous research has shown that circulating levels of fetuin-A were increased in animal models of insulin resistance and diabetes. Additionally, several human investigation studies demonstrate a correlation of fetuin-A levels with body mass index, insulin resistance, and a fatty liver. Recently, the investigators have elucidated the role of fetuin-A phosphorylation in the regulation of insulin action, demonstrating that phosphorylation is critical for the inhibitory activity of fetuin-A. The objectives of this study are twofold: (1) Quantitate phosphorylated fetuin-A levels in individuals with insulin resistance and metabolic syndrome, and (2) Investigate the effects of lifestyle modifications (acute or chronic exercise and dietary modifications) on fetuin-A phosphorylation and insulin sensitivity.

The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults

The prevalence of overweight and obesity in Singapore is approximately half of that in the United States, yet the incidence of type 2 diabetes is similar, and is expected to double in the near future. This indicates that metabolic dysfunction, particularly insulin resistance, is widely prevalent even among individuals who are considered normal-weight or lean by conventional measures, i.e. body mass index (BMI) and percent body fat. These individuals are often referred to as "metabolically-obese normal-weight" (MONW), and have increased risk for cardiometabolic disease despite their normal BMI and total body fat values. The prevalence of the MONW phenotype varies across populations and differs markedly among different ethnicities. However, our understanding of the complex interactions between ethnicity, body composition, and metabolic dysfunction and its reversal remains rudimentary. Previous attempts to characterize the MONW phenotype are confounded by the small but significant differences in BMI or percent body fat between groups (even if all subjects were lean, within the "normal" range), with MONW subjects being always "fatter" than the corresponding control subjects. There are no published studies that prospectively recruited groups of metabolically healthy and unhealthy lean individuals matched on BMI and percent body fat. Furthermore, although weight loss improves body composition and many of the cardiometabolic abnormalities in most obese patients, little is known about the possible therapeutic effects of calorie restriction in MONW subjects. Accordingly, a better understanding of the MONW phenotype and the evaluation of therapeutic approaches for its reversal will have important implications for public health. By facilitating earlier identification of these subjects, who are more likely to go undiagnosed and thus less likely to be treated before clinically overt cardiometabolic disease develops, results from this study will allow for earlier and effective intervention.

The objectives of this trial are to assess the effects of corn oil and coconut oil on low-density lipoprotein cholesterol (LDL-C) concentrations, and other aspects of the fasting lipoprotein lipid profile, as well as insulin sensitivity and an inflammatory marker, in men and women.

The use of natural products in the prevention or treatment of chronic diseases is an emerging field in current medicine. And studying the mechanisms of actions by which natural products act in our bodies contributes to the rational use of these products. And the combination of different natural products such as prebiotics (FOS- fructooligosaccharides, GOS-Galactooligosaccharides and beta-glucans derived from yeast), herbal medicine (Silybum marianum), and minerals (Se-selenium, Zn-Zinc, and Mg-Magnesium), o which would result in a synergistic association between them can contribute to achieving not only preventive effects but treatment for chronic diseases such as diabetes and obesity. The present study aims to study the effects of a composition containing natural products on factors and markers that are part of mitochondrial biogenesis and the neuroimmune-endocrine system in healthy volunteers and that present grade 1 overweight/obesity.

Background Surgical injury provokes a stress response. These pathways mediated by stress hormones and cytokines cause a catabolic state. The loss of body cell mass may result in prolonged convalescence and increased morbidity. Protein catabolism after colorectal surgery is even more increased in patients with type 2 diabetes mellitus. Epidural blockade, by reducing the intensity of the catabolic response, improves substrate utilization after surgery in non-diabetic patients. This effect is even more pronounced in diabetic patients receiving amino acids. The aim of the study is to explore the effect of two different protocols to manage blood glucose control on glucose and protein metabolism in patients with type 2 diabetes mellitus undergoing colon surgery and receiving epidural analgesia and perioperative feeding with amino acids. The following hypotheses are tested: Tight perioperative blood glucose control with intensified insulin therapy compared to standard blood glucose control in presence of general anesthesia with epidural analgesia and amino acid infusion would reduce endogenous glucose production and leucine oxidation. Tight blood glucose control and perioperative infusion of amino acids induce a more positive protein balance compared to standard blood glucose control by better oxidative glucose utilization and redirecting amino acids from oxidative to synthetic pathways. Material and Methods A total of 20 patients with diabetes mellitus type 2 undergoing elective colorectal surgery will be admitted to the study. Patients will be randomly assigned to receive standard blood glucose control (blood glucose target <10 mmol*l-1; control group; cytotoxic T lymphocyte (CTL) group, n=8) or to receive tight blood glucose control with intensified insulin therapy (blood glucose target<6 mmol*l-1; intensified insulin group; II group, n=8). All patients will receive general anesthesia and an epidural catheter for perioperative analgesia. During surgery (intraoperative state) and immediately after surgery (postoperative state) when receiving an amino acid infusion protein and glucose kinetics will be assessed using a stable isotope technique with L-[1-13C]leucine and [6,6-2H2]glucose and circulating concentrations of glucose, glucagon, insulin and cortisol will be measured. The primary endpoints of the study will be protein balance. Sample size is set to ensure at least 80% power at a significance level of 0.05.