138 Clinical Trials for Various Conditions
The purpose of this study is to evaluate the effect of BKR-017 on insulin resistance in type 2 diabetes (T2D) subjects during 28 days of active test product administration.
The purpose of this research is to use a recently developed triple-tracer positron emission tomography (PET) method to study skeletal muscle insulin resistance. Insulin is the hormone made by your body to control the blood sugar level. "Resistance' to insulin could cause poor blood glucose control (blood sugar levels that are higher than normal). We want to use this new method to image (look at) the following three things: 1) how insulin affects blood flow in skeletal muscle 2) how insulin affects glucose (sugar) transport (movement) into muscle, and 3) how insulin affects glucose metabolism (breakdown) in skeletal muscle of healthy individuals. PET imaging is a relatively non-invasive way to obtain a "metabolic picture" of body organs and has been used successfully to study brain, heart and more recently skeletal muscle. In this research study, we will use PET, with three radioactive tracers (markers), to study skeletal muscle glucose transport in individuals with type 2 diabetes mellitus (type 2 DM) and in non-diabetic individuals who are either normal weight or overweight/obese
The goal of this study is to aggressively treat insulin resistance and its clinical manifestations when they first appear in childhood, and to prevent the subsequent progression towards impaired glucose tolerance and type-2 diabetes. In the process of this clinical trial, we will learn more about the early manifestations of insulin resistance, its treatment, and its relationship to obesity and type-2 diabetes through parallel in-vivo and in-vitro studies.
Clearly the effects of diet and exercise are beneficial for obese persons, but the underlying mechanisms for the improvements in metabolic health are not completely clear. Although mounting evidence suggests that alterations in lipid metabolism in persons with abdominal obesity are associated with a several medical complications, including diabetes, little is known about the factors responsible for this effect. The project in this application is designed to examine how the addition of endurance exercise training to a weight-loss program alters whole-body fatty acid availability, uptake, and oxidation as well as the expression of cellular factors that regulate these processes. In addition, we will evaluate whether these alterations are associated with improvements in insulin sensitivity. In the end, these experiments will provide insight into the cellular and whole-body adaptations in fatty acid metabolism in response to weight-loss and exercise training that may lead to enhancement of insulin sensitivity. Identifying relationships between gene expression, whole-body fatty acid metabolism and clinical outcome measurements, such as insulin sensitivity, may lead to improvements in the therapeutic and/or the preventative approach to obesity and its co-morbidities.
This is a single center, prospective randomized double blind, parallel and placebo controlled study to evaluate oxidative stress and inflammation before and after treatment with linagliptin for 12 weeks. We will also, testing whether Linagliptin is an insulin sensitizer.
Type 2 diabetes (T2D) in youth is increasing in prevalence in parallel with the obesity epidemic. In the US, almost half of patients with renal failure have DKD, and ≥80% have T2D. Compared to adult-onset T2D, youth with T2D have a more aggressive phenotype with greater insulin resistance (IR), more rapid β-cell decline and higher prevalence of diabetic kidney disease (DKD), arguing for separate and dedicated studies in youth-onset T2D. Hyperfiltration is common in youth with T2D, and predicts progressive DKD. Hyperfiltration may also be associated with early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Despite the high prevalence and gravity of DKD in youth-onset T2D, widely effective therapeutic options are lacking. The investigators' preliminary data support a strong association between IR and hyperfiltration in youth-onset T2D, but the pathology contributing to this relationship remains unclear. A better understanding of the pathophysiology underlying hyperfiltration and its relationship with IR is critical to inform development of new therapeutics. The investigators' overarching hypotheses are that: 1) hyperfiltration in youth-onset T2D is associated with changes in intrarenal hemodynamics, resulting in increased renal oxygen demand, 2) the demand is unmet by the inefficient fuel profile associated with IR (decreased glucose oxidation and increase free fatty acid \[FFA\] oxidation), resulting in renal hypoxia and ultimately renal damage. To address these hypotheses, the investigators will measure peripheral insulin sensitivity, adipose insulin sensitivity (FFA suppression), glomerular filtration rate (GFR), RPF, and renal oxygenation in youth with T2D (n=60), obesity (n=20) and in lean (n=20) controls. To further investigate the mechanisms of renal damage in youth with T2D, two optional procedures are included in the study: 1) kidney biopsy procedure and 2) induction of induced pluripotent stem cells (iPSCs) to assess morphometrics and genetic expression of renal tissue.
Background: There is general agreement that statin-treatment of patients to lower plasma cholesterol levels can increase the incidence of type 2 diabetes mellitus (T2D) in some individuals1-5. The physiologic mechanism for the increased risk for T2D from statin treatment is unknown but could result from effects on insulin sensitivity or insulin secretion. This study will evaluate how the medication atorvastatin (trade name Lipitor) works in non-diabetic individuals in regards to its effect on insulin sensitivity and insulin secretion to help further understand the possible cause of the increased occurrence of T2D in people who are at risk for T2D. This research study will also examine what metabolic characteristics and variables (for example insulin resistance, high triglycerides, or both) will identify those people at highest risk of statin-induced T2D. The goals of this study are to: 1. determine the effect of high-intensity atorvastatin (40 mg/day) for \~ 10 weeks on insulin sensitivity and insulin secretion (defined with gold standard methods) (PRIMARY OUTCOMES) as well as other glycemic traits (SECONDARY OUTCOMES); 2. compare a number of cardio-metabolic characteristics (e.g. weight, lipids) before, during, and after administration of atorvastatin; 3. determine if significant deterioration of insulin action and/or secretion following statin treatment will be confined to those with baseline insulin resistance (PRE-SPECIFIED SUBGROUP ANALYSES); 4. perform Personal Omics Profiling (iPOP) 6,7 before and after taking atorvastatin to examine treatment-associated changes in all baseline variables and to analyze not only previously-known drug efficacy but also untargeted drug efficacy (EXPLORATORY ANALYSES). General approach: This will be an open-label study to evaluate the diabetogenic effect of atorvastatin (40 mg/day for 10 weeks) on both insulin action and insulin secretion in nondiabetic individuals. To ensure we recruit individuals across a broad range of insulin sensitivity, we will target recruitment to enrich for those with combined increases in LDL-C and TG concentrations (see SIGNIFICANCE and RATIONALE). The experimental population will consist of \~75 apparently healthy, non-diabetic volunteers eligible for statin therapy but without pre-existing atherosclerotic cardiovascular disease. Following baseline assessments of co-primary outcome measures: insulin sensitivity (by insulin suppression test, IST) and insulin secretion (by graded glucose infusion test, GGIT), participants will be placed on a weight maintenance diet and treated with 40 mg/day of atorvastatin. All baseline measurements will be repeated \~10 weeks later with iPOP8 measurements done at baseline, at weeks 2, 4, and 10 on atorvastatin, and at weeks 4 and 8 off atorvastatin.
The overall aim of this pilot study is to investigate the effects of exercise training on skeletal muscle and adipose tissue insulin resistance in subjects with Type 2 Diabetes (T2D).
This study is a randomized, double-blind, placebo-controlled, dose-response study of BKR-017 and placebo that will be conducted at two investigative sites. The total duration of subject involvement is approximately 15 weeks; the screening period can be up to 3 weeks prior to the start of test period, followed by a 12-week test period. During the test period, subjects will self-administer three tablets of test product, two times daily: before breakfast and before bedtime.
The purpose of this study is to evaluate the effects of dapagliflozin on insulin sensitivity
Patients with Type 2 diabetes and severe insulin resistance with very large insulin requirements who have failed all previous insulin regimens using non-concentrated forms of insulin (U100 insulin formulations) will receive 5X concentrated insulin (U500 regular insulin)infused via insulin pump.
The purpose of this research is to obtain blood samples before and after a bariatric procedure to better understand the reasons for glucose intolerance and insulin resistance (diabetes) in the obesity, and the reasons for improvement of diabetes after bariatric surgery
The investigators are doing this study to learn more about how to prevent type 2 diabetes in teenage girls. The purpose of this study is to find out if taking part in a cognitive-behavioral therapy group, exercise training group, or a combination of cognitive-behavioral therapy and exercise training groups, decreases stress, improves mood, increases physical activity and physical fitness, and decreases insulin resistance among teenagers at risk for diabetes.
The current protocol plans to enroll participants with youth-onset Type 2 Diabetes (T2D) as well as obese and lean controls from the Renal-HEIR - Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study (n=100) \[COMIRB #16-1752\] in a prospective investigation that seeks to 1) define the changes in kidney function by gold standard techniques and energetics by functional Magnetic Resonance Imaging (MRI) in adolescents with and without T2D as they transition to young adulthood; 2) quantify kidney oxidative metabolism by 11C-acetate Positron Emission Tomography (PET) in a subset of participants who are ≥18 years of age with youth-onset T2D and/or obesity; 3) determine peripheral arterial stiffness by SphygmoCor. Mechanistic insight will be provided by transcriptomic analyses of repeat biopsies 3-years after their initial biopsy for eligible participants with youth-onset T2D, as well as molecular analysis of tissue obtained from J-wire endovascular biopsies. This study will also leverage this well-characterized cohort of youths to define youth-onset T2D-related changes in brain morphology and function by structural MRI and resting-state functional MRI and through the assessment of cognitive function (fluid and crystallized intelligence) using the NIH Toolbox Cognitive Battery (NIHTB-CB), as an exploratory objective. All enrollees in Renal-HEIR have consented to be contacted for future research opportunities.
Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.
The purpose of this research study is to determine whether continuous glucose monitors (CGM) are a safe, effective, and acceptable way to evaluate type 2 diabetes risk in youth as compared to the standard 2-hour oral glucose tolerance test (OGTT). This study will involve wearing a CGM, wearing a physical activity tracker, responding to surveys, and completing at-home glucose and mixed food challenge while wearing the CGM. Subjects will also be asked to complete an interview by phone or videoconference after wearing the CGM.
Investigators propose to study youth across the spectrum of body mass index (BMI) and dysglycemia. This approach will allow investigators to disentangle the relationship of key features of type 2 diabetes (T2D) risk (e.g. obesity) with intermediary physiologic changes (e.g. insulin resistance, inflammation, β-cell dysfunction and dysglycemia) that pose a risk for the brain. Investigators will determine which of these factors are most associated with differences in brain structure and function among groups, over time, and how these effects differ from normal neurodevelopment.
Rates of type 2 diabetes (T2D) in adolescents have escalated. Adolescent-onset is associated with greater health comorbidities and shorter life expectancy than adult-onset T2D. T2D is preventable by decreasing insulin resistance, a physiological precursor to T2D. T2D prevention standard-of-care is lifestyle intervention to decrease insulin resistance through weight loss; yet, this approach is insufficiently effective in adolescents. Adolescents at risk for T2D frequently experience depression, which predicts worsening insulin resistance and T2D onset, even after accounting for obesity. Mindfulness-based intervention (MBI) may offer a targeted, integrative health approach to decrease depression, and thereby, ameliorate insulin resistance in adolescents at risk for T2D. In a single-site, pilot randomized controlled trial (RCT), we established initial feasibility/acceptability of a 6-week group MBI program, Learning to BREATHE, in adolescents at risk for T2D. We demonstrated feasible single-site recruitment, randomization, retention, protocol adherence, and MBI acceptability/credibility in the target population. Our preliminary data also suggest MBI may lead to greater reductions in stress-related behavior, vs. CBT and a didactic/health education (HealthEd) control group. The current study is multisite, pilot RCT to test multisite fidelity, feasibility, and acceptability in preparation for a future multisite efficacy trial that will have strong external validity, timely recruitment, and long-term follow-up. Adolescents (N=120) at risk for T2D will be randomized to MBI vs. CBT vs. HealthEd and followed for 1-year. Specific aims are to: (1) test multisite fidelity of training and implementation of 6-week group MBI, CBT, and HealthEd, to teens at risk for T2D; (2) evaluate multisite feasibility/acceptability of recruitment, retention, and adherence for an RCT of 6-week group MBI, CBT, HealthEd with 6-week and 1-year follow-up; and (3) modify intervention training/implementation and protocol procedures in preparation for a future, fully-powered multisite efficacy RCT.
The goal of this two-site grant proposal is to determine the role of the decreased insulin-mediated muscle perfusion found in type 2 diabetes in contributing to the development of cardiac and skeletal muscle dysfunction and subsequent functional exercise impairment. In addition, it is also our goal to determine whether exercise training attenuates insulin resistance and restores insulin-mediated perfusion to the heart and to skeletal muscle, leading to improved cardiac function and exercise performance.
The overarching goal of this proposal is to determine whether DNA methylation of the mitochondrial DNA impairs mitochondrial function in insulin resistant states such as overweight/obesity and type 2 diabetes.
This study will investigate the safety and efficacy of the investigational use of the HydraSolve T2D™ System in improving blood glucose control and insulin resistance in patients with obesity (Class 1, BMI 30-39.9 kg/m2) and type 2 diabetes who have not achieved targeted levels of blood glucose control using oral diabetes medications. The previously FDA-cleared (for liposuction and fat transfer) HydraSolve T2D™ System will be used to perform a novel, minimally invasive laparoscopic and mini-laparotomy procedure to selectively remove excess intra-abdominal fat from the mesentery (Mesenteric Visceral Lipectomy (MVL)), while not affecting surrounding tissues. The study will include several weeks of screening for eligibility before the intervention, and 12-months of follow-up post-surgery.
The study is a prospective unblinded randomized trial to evaluate the feasibility of conducting a sleep extension intervention trial and the sleep extension intervention among the young adults. The study also wants to assess whether a sleep-extension intervention has an impact on the insulin resistance levels of young adults. The intervention consists of an education session and to extend the sleep time at least one hour but can be up to 2 hours per night for 4 weeks.
This study pilots the feasibility and acceptability of a family-based lifestyle intervention for decreasing diabetes risk called "Salud sin Barreras" (meaning, "Health without Barriers") delivered in the community to Latino teens at risk for type 2 diabetes. This program combines traditional lifestyle intervention to change eating and physical activity with learning mindfulness-based stress reduction tools. We also are exploring how Salud sin Barreras lowers stress and improves insulin resistance in Latino teens, as compared to lifestyle-only intervention, the "La Vida Saludable" (meaning, the Healthy Living Program; HeLP).
This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D.
Randomized, double blind, placebo-controlled clinical trial examining the efficacy and safety of mifepristone 600 mg daily in male subjects with type 2 diabetes mellitus, not associated with Cushing's syndrome
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes. Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes. This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.
A trial of patients aged 10-24 years with type 2 diabetes mellitus to evaluate the comparative efficacy and safety between dapagliflozin and Placebo.
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes occurs when the cells of the body become resistant to the effects of insulin, and this causes high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed at preventing and treating type 2 diabetes. Mitochondria are cellular structures that are responsible for turning nutrients from food, into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas where they are needed, and can fuse together to form large, string-like, tubular networks or divide into small spherical structures. The name of this process is "mitochondrial dynamics" and the process keeps the cells healthy. However, when more food is consumed compared to the amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a leak of partially metabolized nutrients that can interfere with the ability of insulin to communicate within the cell. This may be a way for the cells to prevent further uptake of nutrients until the current supply has been exhausted. However, long term overload of the mitochondria may cause blood sugar levels to rise and lead to the development of type 2 diabetes. This study will provide information about the relationship between mitochondrial dynamics, insulin resistance and type 2 diabetes.
The role of individual leukocyte populations in type 2 diabetes (T2D) and immunometabolism in general represent important gaps in knowledge to better understand the etiopathogenesis of T2D. Emerging evidence indicates that certain leukocyte populations serve as an important nexus of T2D-associated inflammation. This novel and innovative clinical trial will test the efficacy of a leukocyte-selective anti-inflammatory small drug as adjunctive therapy in improving insulin sensitivity in obese, insulin-resistant type 2 diabetic subjects. This trial also offers a first-in-kind opportunity to better understand the role of specific leukocyte populations in type 2 diabetes. The drug's clinical profile suggests that it will be well-tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo
The investigators seek to examine the metabolic changes that occur amongst obese and lean pregnant women with normal glycemic control as well as pregnant women with diabetes mellitus (gestational diabetes and pre-existing type 2 diabetes mellitus) compared to non-pregnant age matched controls. Given the adaptive tendency of the maternal body to use alternative energy sources such as ketones and free fatty acids rather than glucose and to shunt glucose and amino acids to the fetus, the investigators hypothesize that the amino acid and fatty acid profile will be reflective of this adaptive change and that maternal insulin resistance will result in alterations in this pattern in both the plasma and CSF. Furthermore, the investigators also hypothesize that maternal degrees of insulin resistance will also be reflected in CSF hormonal changes.