Mitigating the Pro-inflammatory Phenotype of Obesity
Blood PressureDiabetes4 moreThe purpose of this study is to examine the hypothesize that 4 weeks of sympathetic nerve activity (SNA) inhibition (oral clonidine) will cause a significant reduction in circulating blood concentrations and endothelial cell expression of inflammatory markers (e.g., TNF-α, IL-6). Our study is a prospective study using a randomized, double-blinded design to test 4 weeks of SNA blockade (oral clonidine) compared with a BP-lowering control condition (diuretic, hydrochlorothiazide) or a placebo.
Dissecting the IMpact of 11-OXygenated and Classic Androgens on Skeletal Muscle Insulin Sensitivity...
Polycystic Ovary SyndromeInsulin Resistance2 moreAndrogen excess is the cardinal biochemical feature of polycystic ovary syndrome (PCOS). Serum testosterone correlates with insulin resistance in PCOS, however, there is an urgent need to improve our understanding of the association between androgens and the risk of type 2 diabetes. 11-oxygenated steroids are the predominant androgens in PCOS and correlate closely with markers of insulin resistance. The bioactive 11-oxygenated androgen 11-ketotestosterone (11KT) binds and activates the androgen receptor with equal affinity to testosterone, yet nothing is known about its impact on metabolism or glucose homeostasis Crucially, there are no data linking androgen excess with muscle glucose metabolism and the differential contribution of 11-oxygenated androgens to diabetes risk through these processes remains unknown. The investigators hypothesise the following: Oral androgen exposure in women with PCOS results in distinct changes in tissue-specific insulin sensitivity and muscle energy biogenesis 11-oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure The study has the following aims: To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS. To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS To compare the differential impact of 11-oxygenated androgen compared to classic androgens on glucose disposal and muscle mitochondrial function The two arms will run in parallel and all participants will undergo identical investigations before and after 7 days of either DHEA or 11KA4. Investigations will include baseline arthrometric measurements muscle biopsy, two-step hyperinsulinaemic euglycaemic clamp, breath sampling. This interventional metabolic phenotyping study will probe the role of classic and 11-oxygenated androgens in metabolic dysfunction in PCOS using gold-standard in vivo metabolic phenotyping techniques. Delineating the distinct contribution of 11-oxygenated androgens, through effects on skeletal muscle biology, to the risk of T2DM is an important step in the process of determining risk of type 2 diabetes in this vulnerable cohort.
Effect of Acute Bout of Exercise on Levels of PAHSA
Insulin SensitivityExercise represents an important tool in the prevention and treatment of metabolic disorders associated with obesity and aging, such as type 2 diabetes and cardiovascular disease. Besides skeletal muscle and its myokinins, the metabolic effects of exercise also rely on the induction of favorable changes in adipose tissue function. For example, adipose tissue is a source of lipokinins from the family of palmitic acid esters of hydroxy fatty acids (PAHSA), which have anti-inflammatory and insulin-sensitizing properties. We have recently shown that 4 months of exercise training increases PAHSA levels in adipose tissue and circulation. However, the mechanisms involved in the induction of PAHSA levels in response to exercise are unknown. The aim of the Effect of Acute Bout of Exercise on Levels of PAHSA (ETAPA) project is therefore to investigate the regulation of PAHSA metabolism in response to both acute and chronic exercise. To achieve this goal, we will employ state-of-the-art analytical methods to measure PAHSA levels in both adipose tissue and circulation of subjects of various ages and adiposity status. The main output of the ETAPA project will be the proof of principle regarding the important role of PAHSA lipokinins in exercise-induced enhancement of insulin sensitivity and the identification of potential drug targets that could be used to further improve PAHSA metabolism for the treatment of metabolic disorders associated with aging or obesity.
Monounsaturated Fatty Acid Supplementation for Overweight and Obese Individuals With Prediabetes...
PreDiabetesInsulin Resistance2 moreThe purpose of this study is to understand and determine whether Palmitoleic acid (POA), monounsaturated omega-7 fatty acid (exists in regular diet), improves insulin sensitivity and decreases liver fat accumulation in humans. Unlike others, the study will use POA as a dietary supplement, rather than complex oils, which contain a significant amount of saturated fat palmitic acid. Palmitic acid has known harmful effects on the body. Hence, eliminating palmitic acid from supplementation of POA might increase its benefits. This trial stems from the preclinical discoveries that POA acting as a fat hormone, has beneficial effects on the liver, muscle, vessels, and fat tissue. Supporting this, higher POA levels in humans have been shown to be correlated with a reduced risk of developing type-2 diabetes and cardiovascular diseases such as heart attacks. In animals, it has been observed that POA improves sugar metabolism in a number of mechanisms related to the liver and muscle. Based on these findings, the design of this study is a double-blind placebo-controlled trial that tests the effects of POA on insulin sensitivity of overweight and obese adult individuals with pre-diabetes.
Complex Effects of Dietary Manipulation on Metabolic Function, Inflammation and Health
ObesityInsulin ResistanceThe purpose of this research study is to 1) understand how some, but not all people with obesity develop obesity related conditions such as type 2 diabetes and cardiovascular disease, and 2) compare the effects of 3 popular weight loss diets (Mediterranean, low-carbohydrate, or a very-low-fat plant-based diet) in people with obesity.
Plasma Trimethylamine N-oxide Elevation Induced by L-carnitine Supplementation and Insulin Resistance...
Insulin ResistanceThe primary aims of the current study: using L-carnitine supplementation modulate the level of plasma trimethylamine N-oxide to assess its effect on circulating cytokines related to diabetes and metabolic syndrome; using simulated night-shift work intervention as a stress factor, explore the effect of circulating metabolites on insulin sensitivity The secondary aim is to evaluate the effect of carnitine supplementation on gut microbiome composition.
Stool Transplantation for Treatment of Insulin Resistance in Morbidly Obese Patients
ObesityMorbid1 moreMore and more people in Canada and around the world are severely (morbidly) obese, and this is associated with a high risk for poor blood sugar control (insulin resistance, IR) and diabetes. Weight loss is often very hard to achieve for morbidly obese patients. Bariatric surgery is a very effective treatment, but it has some risks and is not available to all patients. Therefore, alternative treatments are needed. The gut bacteria (intestinal microbiome) might play a role for the development of obesity and IR. Several studies in animals have shown that transferring stool from lean mice or humans into obese animals could lead to weight loss and improve IR. One human study has confirmed this. The investigators are therefore examining, whether transfer of stool from healthy lean people into morbidly obese patients with IR will improve blood sugar control, weight, and other obesity related parameters. This will be done in a randomized controlled trial. Effects on mental health and the bacterial in the mouth related to gum disease will also be assessed. If successful, fecal transfer could be a new alternative treatment approach for morbidly obese patients or those with IR who do not have access to or do not want to undergo bariatric surgery.
PCOS & Insulin Resistance Exercise Study
Polycystic Ovary SyndromeInsulin ResistanceThis study evaluates the feasibility and metabolic effects of implementing a structured exercise program in women with polycystic ovary syndrome and insulin resistance. Participants will be randomized to either 75 minutes of vigorous exercise or 150 minutes of moderate exercise per week.
Interventions Against Insulin Resistance in Pulmonary Arterial Hypertension
Pulmonary Artery HypertensionThe primary objective of this study is to determine the impact of two interventions against insulin resistance on the composite endpoint of 10% improvement in baseline six minute walk distance or improvement in World Health Organization (WHO) functional class in humans with pulmonary artery hypertension (PAH).
Effect of Pasteurized Akkermansia Muciniphila on Insulin Resistance in Otherwise Healthy Subjects...
Metabolic SyndromePre-diabetes1 moreThe purpose of this study is to demonstrate the efficacy of pasteurized Akkermansia muciniphila (pAKK) in improving insulin sensitivity in hyperglycaemic, but otherwise healthy persons with metabolic syndrome. This is the primary objective of this study. Secondary objectives consist of evaluation of the effects of next generation beneficial microbes on metabolic health, anthropometry and body composition, and safety. Therefore, the trial is designed as a phase 2, randomized, double-blind, placebo-controlled, parallel group, multi-center trial comparing pAKK with placebo in restoring insulin sensitivity in dysglycaemic but otherwise healthy subjects with metabolic syndrome. In total, 144 enrolled participants will attend 6 study visits in total. Study visits may be conducted in the clinic, at home by a Healthcare Professional, or by telephone / telemedicine.