Insulin Sensitivity

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

Many teenagers get too little and late timed sleep. High body weight and diabetes are increasing in teenagers as well. This study plans to learn more about whether improving sleep habits can help improve how the body regulates blood sugar and energy use in teenagers who have higher body weight. To answer this question, the investigators plan to enroll teenagers who get \<7 hours of sleep on school nights and measure changes in blood sugars and energy use after two weeks of typical sleep (sleeping on their normal school schedule) and two weeks of a sleep intervention that includes spending longer time in bed at night, melatonin, and morning light.

The goal of this intervention study is to learn about how weight loss impacts molecular signaling of intermuscular adipose tissue (IMAT) in individuals with obesity. The main question it aims to answer is how inflammatory molecules secreted by IMAT promote muscle insulin resistance and inflammation, and how these same molecules are diminished after weight loss. Following screening visits involving body composition measures, blood testing, strength testing, and a thigh muscle biopsy, participants will go through a 12-week dietary intervention for weight loss. After 12 weeks, this will be followed by the same testing and biopsies that were completed before the intervention. Researchers will then compare outcomes of individuals who lost weight to individuals who did not lose weight.

Study Purpose: The combination of caloric restriction and exercise is the most common first-line treatment for obesity-related disorders, yet we know very little about how these two very different treatments work together. A deeper understanding about mechanisms underlying the health benefits of adding exercise to a weight loss program will not only aid efforts to optimize more effective lifestyle interventions, but it can also uncover novel targets for the treatment/prevention of obesity-related diseases. Although a reduction in body fat is the fundamental adaptation to weight loss, we know almost nothing about the effects that adding exercise has on structural and functional changes within fat tissue that may further enhance metabolic health. This is very important because many obesity-related metabolic health complications are tightly linked with abnormalities in abdominal fat tissue. We argue exercise-induced modifications in abdominal fat tissue will reveal persistent health benefits even if some weight is regained Study Summary: 10% Weight Loss Phase - Subject participation in the study will involve a series of metabolic tests before, at midpoint, and after undergoing a 10% weight loss program (with or without exercise training depending on group randomization). During this, subjects will be randomized into one of two different experimental groups: 1. Moderate Intensity Continuous Training (MICT) exercise group 2. No exercise (control) group Follow-up Phase: After completing the metabolic testing post-weight loss, all study-related diet and exercise supervision will end and subjects will be free to make their own choices regarding diet and exercise/physical activity behavior. Subjects will then be asked to complete follow-up testing at 2-, 4- and 6- months post-weight loss. Total involvement in the study for each subject will likely be about 10-13 months (4-7 months during weight loss phase, 6 months during follow-up phase).

The goal of this clinical trial is to clarify the interaction of central insulin action and physical activity with the immune system. Therefore, participants will undergo bicycle spiroergometer tests. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray. In another trial (NCT06552130) lean participants already have been tested. Significant effects on circulating cytokines could be identified. In this amendment, overweight persons in which brain insulin resistance is expected will be tested.

The primary objective of Study GZQG is to compare the effect of retatrutide and placebo on total clamp disposition index (cDI) after 28 weeks of treatment.

The aim for this clinical trial is to evaluate if colchicine in addition to standard of care improves insulin sensitivity in individuals with type 1 diabetes, systemic low-grade inflammaiton and reduced insulin sensitivity. The insulin sensitivity will be evaluated by a hyperinsulinemic, euglycemic clamp.

This is an 8 to14-week three-arm randomized controlled in children 8 to 12 years old. The main purpose of the study is to evaluate if stevia has benefits for weight control and metabolic function relative to caloric sweeteners, and whether it provides benefits in this regard similar to water.

People who experience repeated bouts of circadian misalignment, such as shift workers, are at higher risk of cardiovascular disease (CVD) and Type 2 diabetes (T2D) compared to daytime workers. However, the mechanism(s) by which shift work and associated circadian misalignment increase CVD and T2D risk are unknown. This project will examine whether elevated plasma lipids are a mechanism by which circadian misalignment impairs vascular function, insulin sensitivity, glucose homeostasis and muscle lipid accumulation, which could be targeted to prevent and treat cardiometabolic disease in people who chronically experience circadian misalignment, which includes more than 20% of the US workforce.

Animal and observational research in humans suggest that specific types of non-nutritive sweeteners (NNS) may impair glycemic control. However, whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.

The goal of this clinical trial is to determine if a weekly delivery of insulin at short intervals lasting up to 2 hours can improve insulin sensitivity and cognition in adults with Alzheimer's Disease. It will also provide information about the safety and feasibility of this intervention. The main questions it aims to answer are: Does the intervention improve insulin sensitivity (how the body uses glucose)? Does the intervention improve cognition, measured by the Montreal Cognitive Assessment (MoCA) and the Revised Memory and Behavior Problems Checklist (RMBPC)? What changes occur in brain glucose uptake (FDG-PET)? Participants will: Receive the intervention once a week for 6 months, with each session lasting up to 2 hours Complete cognitive assessments. Adverse events will be assessed throughout the study.

The study investigates the role of one single bout of exercise in mediating enhancement of muscle insulin sensitivity following a single bout of exercise. Furthermore, the study is aiming to elucidate the temporal development in insulin signaling, at the early timepoints of insulin stimulation that may be responsible for the enhanced muscle insulin sensitivity. This will be investigated in young healthy males subjected to a one-legged knee-extensor exercise followed by a hyperinsulinemic-euglycemic clamp, a setup known to enhance muscle insulin sensitivity.

the aim of this study is to investigate the effect of aerobic exercise versus the effect of added sugar elimination on the insulin sensitivity and testosterone levels in females with polycystic ovarian syndrome via measuring the level of 6 hours fasting HOMA-IR and free testosterone before and after 3 months from starting the protocol. All patients were diagnosed as polycystic ovary syndrome with low insulin sensitivity levels

Insufficient sleep and circadian misalignment are independent risk factors for the development of obesity and diabetes, yet few strategies exist to counter metabolic impairments when these behaviors are unavoidable. This project will examine whether avoiding food intake during the biological night can mitigate the impact of circadian misalignment on metabolic homeostasis in adults during simulated night shift work. Findings from this study could identify a translatable strategy to minimize metabolic diseases in populations that include anyone working nonstandard hours such as police, paramedics, firefighters, military personnel, pilots, doctors and nurses, truck drivers, and individuals with sleep disorders.

Diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in people with type 1 diabetes and are exacerbated with longer duration of diabetes and time outside goal glycemic range. Yet, type 1 diabetes is a complex disease with pathophysiology that extends beyond beta-cell injury and insulin deficiency to include insulin resistance and renal vascular resistance, factors that accelerate cardiovascular disease risk. We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections or standard insulin pumps. However, metformin's effect on kidney and endothelial outcomes, and the effects of type 1 diabetes technologies, with or without metformin, on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin delivery and decrease peripheral insulin exposure while improving time in target range and reducing hypoglycemia. We hypothesize that automated insulin delivery systems, particularly when combined with metformin, may modulate renal vascular resistance and insulin sensitivity, thereby impacting cardiometabolic function. MANATEE-T1D is a randomized, double-blind, placebo-controlled trial of 4 months of metformin 2,000 mg daily in 40 youth aged 12-25 years with type 1 diabetes on automated insulin delivery systems vs. 20 control youth with type 1 diabetes on multiple daily injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor which will assess for changes in calculated renal vascular resistance and gold standard measures of whole-body and adipose insulin sensitivity, arterial stiffness, and endothelial function.

To evaluate the effect of estradiol with or without a prior gonadotropin releasing hormone analogue on insulin sensitivity and vascular function in transgender females compared to cisgender controls.

This study aims to evaluate the effect of hepatic ultrasound treatment on changes from baseline in whole-body insulin sensitivity during a hyperinsulinemic, euglycemic clamp (HE Clamp).

This is a parallel randomized controlled trial for the treatment of dry eye disease. The main objective is to investigate the efficacy and safety of the use of insulin eye drops in the control of moderate-severe dry eye disease. Topical insulin drops will be compared to artificial tears in improving the ocular surface interface in patients with dry eye disease over 1 year period.

The primary aim of this study is to evaluate if a single bout of AM vs PM resistance exercise has different effects on insulin sensitivity and sleep. A randomized cross-over trial be used to compare resistance exercise at two different times of the day. Each condition will take place in a laboratory setting. Each condition will consist of exercise, overnight sleep, and oral glucose tolerance tests the following day. The AM exercise will occur \~1.5 hours after habitual wake, and PM exercise will occur \~11 hours after habitual wake. After a 2-6 week washout, participants will complete the other condition. The hypothesis is that PM exercise will be more beneficial than AM exercise in improving insulin sensitivity. This study could identify if there is a better time of day to perform resistance exercise to decrease risk of developing Type 2 Diabetes Mellitus.

The overarching goal of the current study is to investigate the effect of GLP-1 on brain insulin responsiveness in a randomized, single-blinded, within subject cross-over study design. To this end, investigators will compare the effect of the administration of semaglutide versus placebo, followed by an fMRI with administration of intranasal insulin or placebo.

Metabolic flexibility is a process in which the body can switch energy substrates in different physiological states. This flexibility plays an important role in an individual's health because losing it increases the risk of obesity, metabolic syndrome, insulin resistance, and type 2 diabetes. Considering that humans spend most of their awakening hours in a postprandial (PP) state, an organism's metabolic flexibility (MF) to respond to a standardized meal's consumption would provide information on the individual's metabolic health. The PP response to glucose following an oral glucose tolerance test or consumption of a high-carbohydrate meal is well described; however, few studies assess the FM and PP metabolome using mixed meals with different macronutrients. The investigators address how metabolic flexibility and metabolome change after consuming standardized meals with different macronutrient ratios. Data collection includes clinical and diet information, indirect calorimetry, and capillary blood sampling during fasting and after consumption of standardized meals. Samples are collected weekly for one month. The data will determine the metabolic flexibility and metabolome after consuming standardized meals with different macronutrient ratios.

In humans, insulin is secreted in pulses from the pancreatic beta-cells, and these oscillations help to maintain fasting plasma glucose levels within a narrow normal range. Given the fluctuations in insulin concentrations, oscillations enhance precision of control. The hyperinsulinemic euglycemic clamp test (clamp) involves a continuous infusion of insulin and is the gold standard for measuring insulin sensitivity. In this study, insulin sensitivity measured using the standard clamp will be compared with a clamp in which the same total amount of insulin as the standard clamp is infused every five minutes instead of continuously.

The overall goal is to determine how a sleep extension intervention (increasing time in bed) in individuals who maintain less than 6.5 hours sleep per night affects their plasma ceramides and insulin sensitivity. Participants will undergo a randomized controlled trial, with sleep extension (intervention) and healthy lifestyle (control) groups. The sleep extension is designed to increase participant's time in bed by 2 hours per night. Alternatively, the control group will receive basic health information (e.g., physical activity, goal setting, and nutrition when eating out).

The overall goal is to examine the efficacy of a circadian intervention in people with overweight and obesity and habitual short sleep duration (HSSD). Participants will undergo a randomized controlled trial, with circadian intervention and control (healthy lifestyle) groups. The circadian intervention is designed to reduce nighttime light exposure and after-dinner snack food intake. Alternatively, the control group will receive basic health information (e.g., physical activity, goal setting, and nutrition when eating out).

The investigators are studying the pathophysiologic links between obesity, insulin resistance (IR), adipose tissue infection, and post-acute sequelae of COVID-19 (PASC). This study looks at whether adipose (fat) tissue contributes to PASC by driving chronic inflammation or by serving as a reservoir for SARS-CoV-2 persistence. The results will not only determine whether obesity and IR are risk factors for PASC, but will also define fundamental biology that sets the stage for the investigation of novel or existing therapies that target the causal pathways identified.