Insulin Resistance Clinical Trials

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for muscle insulin resistance, although it has been shown that raising FFA with Intralipid can cause muscle insulin resistance within 4 hours. The investigators do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators propose to alter the profile and concentrations of FFA of healthy, non-obese adults using an overnight, intra-duodenal palm oil infusion vs. an overnight intra-duodenal Intralipid infusion (both compared to saline control). The investigators will compare the muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates, providing the first measure of how different FFA profiles alter muscle FFA trafficking and insulin action at the whole body and cellular/molecular levels. By identifying which steps in the insulin signaling pathway are most affected, the investigators will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance. Hypothesis 1: Palm oil infusion will result in abnormal FFA trafficking into intra-myocellular ceramides and abnormal insulin signaling. Hypothesis 2: Intralipid infusion will result in abnormal FFA trafficking into intra-myocellular saturated DG and abnormal insulin signaling. Read Less

This 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 evidence of insulin resistance (i.e., fasting hyperinsulinemia plus prediabetes and/or impaired fasting glucose and/or Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] score >=2.73), and 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. Read Less

With this study the investigators want to understand the physiological differences for people developing pre-diabetes and diabetes. The investigators hypothesize that different individuals go through different paths in the development of the disease. By understanding the personal mechanism for developing disease, the investigators will find a personalized approach to prevent that development. The investigators are also hoping to be able to find a biomarker that will pinpoint to the particular defect and thus, diagnose the problem at an earlier stage and have the information to give personalized diet recommendations to prevent the development of diabetes more effectively. Read Less

The purpose of this project is to examine the impact of increases in brain insulin on sympathetic nervous system activity, as well as peripheral and cerebral blood flow in humans. Read Less

Disordered sleep is a health issue with significant impacts on physical and psychological well-being that has increased in prevalence, but its impact on transgender adolescents has not been fully quantified. While there is found to be an impact of sex steroids on sleep, and sex-dependent differences in the impact of sleep duration and quality on insulin resistance (IR), there is limited available information regarding the impact of Gender Affirming Hormone Therapy (GAHT) for transgender individuals on sleep and IR. Our study aims to quantify the impacts of GAHT on sleep and IR in the pediatric transgender population as well as determine the degree of correlation of sleep to IR in this population. Read Less

The objective of this project is to determine if mTORC1 inhibition by 24 weeks of daily (0.5 mg/day) or weekly (5 mg/week) everolimus can safely improve physiological and molecular hallmarks of aging in humans. Participants who are 55-80 years old and insulin resistant or prediabetic will be randomized to treatment and can expect to be on study for up to approximately 38 weeks. Participants aged 18-35 will not receive the intervention and can expect to be on study for up to approximately 8 weeks. Read Less

This study is designed to determine the impact of extending sleep duration on glucose metabolism in people with obesity. Half of the participants will be instructed to increase their time-in-bed by one hour (sleep extension) while the other half will be be instructed to maintain their current sleep habits. Read Less

To determine if Inositol, a dietary supplement, will improve ovarian and adrenal androgen excess in women with Polycystic Ovarian Syndrome(PCOS). Read Less

The 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. Read Less

A combination of generally regarded as safe (GRAS) compounds named GLY-LOW, which included: alpha lipoic acid, pyridoxamine, nicotinamide, piperine and thiamine, were examined in pre-clinical experiments. GLY-LOW supplementation reduced caloric intake and increased insulin sensitivity in mice. In female mice, GLY-LOW supplementation reversed aging-related declines in female hormones. Studies in humans are needed to examine the feasibility, utility and efficacy of GLY-LOW supplementation in post-menopausal women with obesity toward improving aging-related impairments. The effect of GLY-LOW supplementation on these obesity and biological age-related impairments in post-menopausal adult female humans with obesity is unknown. We aim to translate the findings of GLY-LOW supplementation in animals to a cohort of healthy, postmenopausal females at birth with obesity by conducting a one-group, no-placebo comparer, pre post intervention clinical trial. Additionally, we propose to examine the specific effect of supplementation by GLY-LOW on biological aging via retina scan. The objectives of the proposed pilot study are: I. Conduct a 6-month pilot study to examine the feasibility, utility and efficacy of GLY-LOW supplementation in a total of 40 postmenopausal female born adults > 55 years with obesity (> 30 BMI) Ia. Examine alterations in self-reported caloric intake and the following health and biological aging, parameters prior to and after 6 months of GLY-LOW supplementation: Self-reported Caloric Intake Metabolic disease risk Cardiovascular disease risk Metabolic assessments Hormones Physical Function and Fitness Muscular strength Cognitive Function and Depression assessments Systemic inflammation Biological aging Safety parameters (also every 2 months during the intervention; ECG at baseline and 2 months only) 12, Compliance measures (pill counts and interviews every 2 months during the intervention) Read Less

The goal of this study is to collect more information from people with plaque psoriasis and to determine if insulin plays a role in the pathogenesis of psoriasis. The main question it aims to answer is if insulin action is preserved or even enhanced in psoriatic lesions despite insulin resistance elsewhere. Participants with plaque psoriasis will have punch biopsies taken of lesional and non-lesional skin after an overnight fast and then during an oral glucose tolerance test. Biopsy specimens will then be assessed for markers of insulin action. Read Less

The primary goal of this study is to determine the dose of fatty acids that acutely induces mild insulin resistance in healthy volunteers. We hypothesize that a low-dose of fatty acid infusion (Intralipid/heparin) will cause a mild insulin resistance. The dose of fatty acid infusion that reliably causes mild insulin resistance will be selected for use in future studies. Read Less