Pancreatic Clamp in NAFLD
Insulin ResistancePrediabetic State3 moreThis is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the specific dose-response impact of insulin infusion rate (IIR) on blood glucose levels during a pancreatic clamp study. The investigators will recruit participants with a history of overweight/obesity and prediabetic state (i.e., prediabetes or impaired fasting glucose, with fasting hyperinsulinemia), with evidence of, or clinically judged to be at high risk for, uncomplicated non-alcoholic fatty liver disease (NAFLD). Participants will undergo two pancreatic clamp procedures in which individualized basal IIR are identified, followed in one by maintenance of basal IIR (maintenance hyperinsulinemia, MH) and in the other by a stepped decline in IIR (reduction toward euinsulinemia, RE). In both clamps the investigators will closely monitor plasma glucose and various metabolic parameters. The primary outcome will be the absolute and relative changes in steady-state plasma glucose levels at each stepped decline in IIR.
Effect of Alpelisib in Healthy Volunteers
Insulin ResistanceHyperinsulinemia1 moreThe goal of this clinical trial is to test a single dose of the phosphoinositide-3-kinase (PI3K) inhibitor alpelisib versus placebo in healthy volunteers. The main questions it aims to answer are the impact of acute alpelisib-induced insulin resistance on parameters of glucose and lipid metabolism (how healthy people respond to temporary insulin resistance so that the investigators can see what happens to how the liver handles fat and sugar). Participants will: Consume their total calculated daily caloric needs in nutritional supplements, divided in three meals, and otherwise fast for 24 hours Take a dose of alpelisib 300 mg or placebo at bedtime Wear a continuous glucose monitor for 72 hours Participate in an oral glucose tolerance test (OGTT) Researchers will compare blood tests before and during OGTT in participants randomized (like the flip of a coin) to alpelisib versus placebo to see how the drug treatment affects plasma glucose, serum insulin, and serum lipid parameters (triglycerides, free fatty acids, and apolipoprotein B).
Abscisic Acid Effects on Glucose Homeostasis and Insulin Sensitivity
Pre DiabetesThe purpose of this study is to determine the effects of oral abscisic acid (ABA) on glucose metabolism in subjects with defined prediabetes.
Enhancing Brain Health by tDCS in Persons With Overweight and Obesity
Insulin ResistanceObesity1 moreDisturbances in the hypothalamus communication pathways with other regions in the brain and the periphery may represent a potential link between metabolic and cognitive health. The current project evaluates whether enhancing synaptic plasticity of this pathway can improve weight management, insulin sensitivity, and cognitive functions. In recent studies, we were able to show that the human brain is sensitive to insulin with favorable effects on peripheral metabolism and cognition. These brain regions encompass the hypothalamus and its connections to the striatum and prefrontal cortex. We want to investigate whether it is possible to enhance neuroplasticity of insulin-responsive brain regions to suppress the weight gain trajectory and improve dopamine-dependent cognitive functions in people with a high risk to develop type 2 diabetes. For this purpose, neuroimaging tools using high-definition transcranial direct current stimulation (HD-tDCS) and magnetic resonance imaging (MRI) will be implemented to assess synaptic plasticity of a neural network essential for metabolic and cognitive health.
Improving Glycemic Control With Electrical Stimulation in Mexican-Americans
ObesityOverweight1 moreOnce written consent is obtained, the participant will be provided with an accelerometer to be worn for 7 days to assess current physical activity levels. Subjects will be provided with a standardized diet (55/15/30% CHO/PRO/FAT) prior to collection of pre-intervention data of insulin sensitivity. Individuals will then participate in an 8-week electrical stimulation intervention (30min/day, 3x/week) and randomized into placebo/control, NMES, resistance training combined with NMES (RT +NMES), or resistance training (RT) group (n=15 per group), followed by collection of post-intervention data. The control group will receive electrical stimulation up to sensory level, the NMES group will receive stimulation up to tolerable intensity to induce visible muscle contraction, the RT+ NMES will receive stimulation up to tolerable intensity during resistance training, and the RT group will only receive exercise training. Pre-and post-intervention data includes measurements for body composition, resting metabolic rate, VO2max, insulin sensitivity, and comprehensive blood work.
Effects of Obesity and Intensity of Exercise on Ghrelin Levels
ObesityInsulin Resistance1 moreThis study is investigating the effect of different intensities of exercise on levels of the hormone, ghrelin. In addition, we will be examining the relationship between any exercise induced changes in ghrelin and insulin sensitivity, obesity, and vascular function.
Exercise in Adolescents With Insulin Resistance
Insulin ResistanceThe 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.
Study Testing Benefits of Ursolic Acid (UA) as a Countermeasure To Myopenia and Insulin Resistance...
Spinal Cord InjuriesTetraplegia5 moreThis study will evaluate if Ursolic Acid supplementation may be effective in reducing muscle loss and improving blood sugar control in the SCI community.
The Effects of an Obesogenic Lifestyle in Recreationally Active, Young Adults
Insulin ResistanceImpaired Glucose Tolerance2 moreThe goal of this clinical trial is to learn about the alterations insulin resistance and metabolic flexibility following a transition to an obesogenic lifestyle in fit young men. The main questions it aims to answer are: Does the addition of excess carbohydrates when transitioning to a sedentary lifestyle promote insulin resistance in fit young men? Does the addition of excess carbohydrates when transitioning to a sedentary lifestyle lower the body's ability to break down fats and carbohydrates in fit young men?
Metabolic Effects of Angiotensin-(1-7)
ObesityInsulin Resistance2 moreThe overall purpose of this study is to learn more about the metabolic effects of angiotensin-(1-7) in the insulin resistant state associated with obesity. Pharmacologic approaches to increase angiotensin-(1-7) levels or its actions are currently in development for treatment of metabolic-related diseases such as obesity and type II diabetes, based on findings from animal studies. It is unclear if this peptide contributes to the regulation of metabolism in humans. The investigators will test if angiotensin-(1-7) infusion can improve insulin sensitivity measured by hyperinsulinemic-euglycemic clamp methods in individuals with obesity and insulin resistance. The investigators will also examine for changes in blood pressure and related hemodynamic and hormonal changes following angiotensin-(1-7) infusion.