Brain Metabolism in Polycystic Ovary Syndrome
Insulin ResistanceThe purpose of this study is to investigate whether higher insulin resistance in young women with Polycystic ovary syndrome (PCOS) is associated with reduced cerebral metabolic rate of glucose (CMRglu). Brain volumes using magnetic resonance imaging (MRI) and quantitative cerebral glucose uptake using dynamic positron emission tomography (PET) were obtained.
New IR Biomarkers (Myokines) in Colombian People
Insulin ResistanceDiabetes Mellitus1 moreAround the world, the prevalence of type 2 diabetes mellitus (T2DM) has been increasing since the last two decades, with approximately 347 million patients with diabetes by 2013 according to the World Health Organization (WHO). This pronounced increase is due to an increase in the prevalence of obesity, reduction in physical activity levels, accelerated urbanization and aging of the population. In Colombia, T2DM ranks fifth in the main morbidity and mortality causes, including only deaths caused directly and without adding the strong influence that T2DM has on cardiovascular disease mortality. Insufficient tissue response to normal insulin concentrations, called insulin resistance, is one of the central pathophysiological mechanisms in the development of T2DM. However, there is currently no simple, practical, safe and reproducible method that allows the diagnosis or identification of insulin resistance, nor the follow-up to its evolution. At the moment, the gold standard for assessing the degree of insulin sensitivity or resistance is the "hyperinsulinemic-euglycemic clamp", a laborious technique, of high cost and high technical difficulty, requiring specialized personnel and hospitalization. Non-invasive methods based on mathematical regressions, such as the Homeostatic Model Assessment (HOMA-IR), are imperfect and widely variable, and have not been validated in the Latin American population, less Still Colombian. Therefore, the development of new, easily obtainable quantitative tools for the diagnosis of insulin resistance is required. This requires not only the identification of new and better biomarkers, but also the determination of their diagnostic performance and operational characteristics. This project will investigate 3 molecular targets (myokines), novel and easy to measure, with high probability of being good biomarkers of insulin resistance. The research will include validation of its association with insulin resistance measured by the reference method, as well as its measurement in apparently healthy individuals. Finally, operator-receiver characteristics of each test will be analyzed, in order to propose a cutoff point for the diagnosis of insulin resistance.
Microbiome Insulin Sensitivity Study
ObesityInsulin Resistance1 moreThe Microbiome Insulin Sensitivity Study "MISS" is a pilot study designed to study microbiome composition across puberty and how it relates to insulin sensitivity and secretion in obese girls, who are at increased risk for developing type 2 diabetes in puberty. The investigators will evaluate the gut microbiome composition in fecal samples of 57 obese girls in three groups: prepubertal (Tanner 1), early pubertal (Tanner 2-3), and late pubertal (Tanner 4-5). Insulin sensitivity will also be measured via an intravenous glucose tolerance test (IVGTT) in 18 prepubertal and late pubertal participants.
MicroRNA as Biomarkers for Development of Metabolic Syndrome in Women With Polycystic Ovary Syndrome...
Polycystic Ovary SyndromeInsulin ResistanceThe aim of this study is to explore the microRNA profile in serum of women with Polycystic Ovary Syndrome and investigate the correlation between the microRNA profile and markers of metabolic syndrome.
Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans
Insulin SensitivityInsulin Resistance1 moreParticipants will be randomly allocated to either Yakult ingestion or a control group. For the first 20 days, subjects will consume their normal diet (keeping a detailed food diary throughout). On days 21-28 they will switch to a high-fat/high-calorie diet. The investigators hypothesise that consuming a high-fat, high-energy diet for 7 days will alter the composition of the gut microbiota and induce metabolic endotoxaemia / systemic inflammation as well as decreasing whole body insulin sensitivity (as we have shown previously). In contrast, the investigators hypothesise that consuming Yakult for 21 days before and 7 days throughout the high-fat diet will maintain a favourable gut microbiota and prevent metabolic endotoxaemia / systemic inflammation and thus maintain insulin action / insulin sensitivity.
Effect of Consumption of Non Caloric Sweeteners and Insulin Sensibility
Insulin SensitivityThis study will compare the effect of acute consumption of two carbonated drinks, sweetened with sugar or with non-caloric sweeteners, over the insulin response of healthy adults who normally consumed foods or drinks that contain non-caloric sweeteners
Impact of Muscle Insulin Resistance on the Pathogenesis of Non Alcoholic Steatohepatitis
Non Alcoholic Fatty Liver Diseases (NAFLD)The incidence of Non alcoholic fatty liver disease (NAFLD) continues to increase, and prevalence estimates for NAFLD range from 17-33%, making it is the most common cause of chronic liver disease in North America. It is associated with increased cardiovascular morbidity as well as progression to cirrhosis is a subset of patients. There is currently no approved treatment for NAFLD. A key barrier to the development of effective therapies is a lack of consensus on the criteria for diagnosis and endpoints for studies evaluating diagnostic markers, prognosis and therapeutic modalities. NAFLD encompasses an entire pathological spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive non alcoholic steatohepatitis (NASH) associated with inflammation, fibrosis, and necrosis. It has been estimated that 20-30% of patients with NAFLD will exhibit biochemical and histological changes characteristic of NASH, and 15-20% of those patients will progress to have cirrhosis. NASH remains an important phenotypic state, because this sub-group of patients is deemed at high-risk for developing progressive disease resulting in cirrhosis, liver failure requiring transplantation, or death. Although NAFLD has not to date been included as a component of the metabolic syndrome, there is increasing evidence that NAFLD frequently accompanies the development of insulin resistance and therefore may be an indicator or predictor of future cardiometabolic risk. Moreover, recent findings in skeletal muscle of experimental insulin resistance (lipid infusion) as well as naturally occurring obese and type 2 diabetic, insulin resistant patients show that skeletal muscle inflammation leads to a pattern of extracellular matrix, structural, and remodeling abnormalities that closely resemble the TGFb, connective tissue growth factor (CTGF) mediated fibrotic response that differentiates simple steatotic liver from NASH. This suggests there may be a common underlying mechanism. Given the ready availability of skeletal muscle tissue using percutaneous needle muscle biopsies, compared to the more invasive liver biopsy, it may be possible to use characteristics of skeletal muscle to distinguish the severity of liver fibrosis. Given the preponderance of patients being identified with NAFLD, the recognition of less and non invasive tests that help to discriminate the different phenotypic types of NAFLD would be highly practical and useful. This would help identify patients at risk of progression to cirrhosis, and thus make them the target of any available therapeutic interventions. The investigators hypothesize that 1. Insulin resistance measured through glucose tolerance test directly correlates with the extent of liver and muscle fibrosis, and 2. Inflammation and fibrosis in the skeletal muscles correlates with the histopathological changes seen in patients with NAFLD, and potentially skeletal muscle inflammation may be used as a diagnostic predictor to differentiate patients with NASH from patients with simple steatosis. The overall goal of this project is to determine the extent to which inflammation and fibrosis in skeletal muscle mirrors and is predictive of the level of liver inflammation and can distinguish NASH from simple steatosis. Specifically, the investigators propose the following Aims: To use estimates of insulin sensitivity from modeling of oral glucose tolerance tests to test the hypothesis that the extent of liver and muscle fibrosis is directly related to insulin resistance. To use liver and muscle biopsies to characterize the changes in abundance of mRNAs and proteins that characterize inflammation, extracellular matrix remodeling, and fibrosis. The investigators will use quantitative rt-PCR and immunoblot analysis to compare mRNA expression and protein abundance of collagens I and III, fibronectin, and connective tissue growth factor (CTGF) to test the hypothesis that there is a direct relationship between the levels of these proteins in muscle and liver and the degree of fibrosis. To establish a biospecimen repository of serum, mRNA from circulating white blood cells, liver and muscle tissue, and DNA to serve as the substrate for future studies of the pathogenesis of NASH.
Neural Functioning of Feeding Centers in Obese Youth
ObesityInsulin ResistanceTo explore whether obese adolescents with insulin resistance and relative low leptin levels exhibit functional alterations of the neuronal circuits involved in the regulation of energy metabolism and food seeking behaviors. We here propose to test the hypothesis that the reward circuitry is dysregulated in obese adolescents and is related to the degree of insulin resistance and hyperinsulinemia.
IRAPs (Secreted Insulin Regulated AminoPeptidase): a New Insulin Sensitivity Biomarker
Insulin ResistancePrevious studies have demonstrated defects in the trafficking and translocation of GLUT4 glucose transporter in skeletal muscle and adipose tissue to be a major cause of insulin resistance in humans. IRAP (Secreted Insulin Regulated AminoPeptidase) is a protein which collocalizes and is translocated with GLUT4 to the plasma membrane in response to insulin. The extracellular domain of IRAP is cleaved and released in the bloodstream. Therefore, IRAP plasma concentration could be a good marker of insulin sensitivity. In this study the investigators seek to confirm this hypothesis by using the gold standard of insulin sensitivity assessment: the hyperinsulinemic-euglycemic clamp. It is a multicenter descriptive study.
Effect of Omega-3 Fatty Acids on Insulin Sensitivity in Chinese Type 2 Diabetic Patients
Type 2 DiabetesInsulin ResistanceThis study is to examine the change of fasting insulin, glucose, insulin sensitivity and related traits in response to the six month treatment of omega-3 fatty acids, including fish oil and flaxseed oil, in Chinese type 2 diabetic patients. Corn oil, rich in omega-6 fatty acids, will be selected as a controlled oil. The investigators hypothesize that omega-3 fatty acids could improve insulin sensitivity and glucose metabolism in Chinese type 2 diabetic patients.