274 Clinical Trials for Various Conditions
This will be a validation study of Quantose IR and Quantose IGT to predict insulin resistance and identify patients with prediabetes. This is a pilot study of 100 subjects. Based on the results of this initial trial, investigators plan to perform a larger trial at UTMB. Quantose IR is a fasting blood test for insulin resistance and prediabetes, and is clinically validated in non-pregnant individuals. The Quantose IR Score is based on three novel nonglycemic biomarkers, as well as insulin, and provides a comprehensive measure of insulin resistance. These analytes include: * α-HB (α-hydroxybutyrate): positively correlated with insulin resistance and indicative of early β-cell dysfunction. * L-GPC (linoleoyl-glycerophosphocholine): negatively correlated with insulin resistance and impaired glucose tolerance. * Oleic Acid: positively correlated with increasing lipolysis and insulin resistance. * Insulin: increased insulin is characteristic of insulin resistance and is an independent risk factor for type 2 diabetes and cardiovascular disease. Quantose IGT is designed to estimate the risk of being IGT. It is calculated from a multiple logistic regression model based on the fasting plasma levels of: * Glucose. * α-HB. * β-HB. * 4-methyl-2-oxopentanoic acid. * LGPC. * Oleic acid. * Serine. * Vitamin B5. Participants in the study will be consenting to data collection and two visits for lab draw. The investigators will then evaluate the performance of the Quantose IR and Quantose IGT in the study population.
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.
Glucocorticoids are known to cause an increase in insulin resistance, leading to hyperglycemia, in both diabetic and non-diabetic patients. In both the inpatient and outpatient setting, steroids are used for their anti-inflammatory property to treat a variety of conditions. There is a paucity of information regarding the best way to treat steroid-induced hyperglycemia. In this study we will compare (1) the addition of NPH insulin, an intermediate-acting insulin, given at the time of steroid administration to the patient's standard basal/bolus insulin to (2) modification of the standard basal-bolus insulin regimen which will consist primarily increasing the prandial doses at lunch and supper in order to determine which regimen is superior for glycemic control.
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 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 study is to assess the effects of adiposity on resistance to insulin's ability to suppress hepatic glucose production and to stimulate peripheral glucose metabolism in adolescents with type 1 diabetes. In addition, this study will also examine the role of fatty liver disease on the insulin resistance of obesity in adolescents with type 1 diabetes.
The purpose of this study is to determine the key factors influencing insulin sensitivity in type 1 diabetes (T1DM) and maturity onset diabetes of the young, type 2 (MODY2). Our study tests the hypothesis that decreased insulin sensitivity is primarily driven by chronically elevated insulin levels in the blood rather than chronic elevations in blood sugar.
24 children (12 African-American, Hispanic, or American Indian, 12 Caucasian) previously diagnosed with type 1 diabetes mellitus will participate in this pilot study to evaluate the presence of hepatic and peripheral insulin resistance. The investigators will use this pilot information to test the hypothesis that insulin resistance occurs in some children with type 1 DM, is secondary to underlying risk factors, and is responsible for increased insulin needs. Methods will include a "step-up" hyperinsulinemic euglycemic clamp and infusion of the stable isotope 6,6-\[2H2\]-glucose. Patient and parent interviews will be conducted to gather information about nutritional intake, ethnicity, family history, and socioeconomic status. The investigators will also measure inflammatory cytokines and free fatty acids to determine whether they are associated with differences in insulin resistance among type 1 diabetes mellitus patients.
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.
Background: Patients who are pre-diabetic or have adult onset (type 2) diabetes have a significantly greater risk of developing heart, blood vessel, or kidney diseases. Recent studies have shown that abnormalities in white blood cell function may increase the chances of developing insulin resistance, the underlying problem in diabetic or pre-diabetic patients. Objectives: To determine levels of insulin sensitivity in selected volunteers. To compare the white blood cells of non-diabetic, pre-diabetic, and type 2 (adult onset) diabetic volunteers to evaluate possible differences in white blood cell function. Eligibility: Individuals between 21 and 60 years of age who (1) are non-diabetic, (2) are pre-diabetic (glucose intolerant or insulin resistant), or (3) have type 2 diabetes that is controlled by diet and/or medications other than insulin. Design: Evaluations before treatment: * Blood tests, including screening procedures for blood-transmitted diseases such as hepatitis B and C, insulin sensitivity and glucose tolerance tests, and liver and kidney function tests. * Pregnancy tests for women of childbearing age. Two tests will be performed during the study period: * Glucose tolerance test to determine how well the body uses glucose. * Blood drawn to study white blood cells. Participants will be financially compensated for the time spent during the study.
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.
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.
Despite advancements in care, most adolescents with T1D have higher BMI and significantly higher HbA1c than recommended and are markedly IR, placing them at increased risk for CVD1,2. Thus, alternative approaches to improve and maintain glycemic control, IR, and BMI for adolescents with T1D are urgently needed. This proposal moves beyond the current insulin and carbohydrate counting-focused lifestyle change paradigm to focus on sleep and circadian misalignment, which will allow for identification of new mechanisms that can be directly translated into future intervention and prevention trials. The goal of the current study is to utilize multiple objective measures of sleep duration, timing (actigraphy), and circadian rhythm (melatonin) in adolescents with type 1 diabetes (T1D; N = 40) and examine relationships with glycemic control, IR, vascular health, and BMI. Further, qualitative methodology will be used to identify barriers and facilitators to healthy sleep in adolescents with T1D.
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.
Background: Type 2 diabetes is a chronic disease that puts individuals at risk for serious health problems like heart disease, kidney failure, vision problems, and stroke. A major way that type 2 diabetes occurs is through insulin resistance. Insulin resistance means that insulin (an important hormone in the body to keep blood sugar normal) isn t working as well as it should, which can lead to problems with high blood sugar. Insulin resistance has been linked to mood problems, stress, and depression, especially in women. To determine if group programs can help reduce the risk for type 2 diabetes, researchers want to look at teenage girls who are at risk for developing the disease. Objectives: To test whether a group program designed to improve mood also can help improve insulin resistance in teenage girls who are at risk for developing type 2 diabetes, or whether a group program that teaches healthy living skills is just as helpful. Eligibility: Teenage girls between 12 and 17 years of age who are at risk for developing type 2 diabetes. Design: * Participants will have two screening visits to find out if they are eligible to take part in the study. The first visit takes about 3 hours and will involve a physical exam, medical history, questionnaires and an interview about mood problems and possible depression. The second visit takes about 6 hours and will involve a full body scan to measure muscle and fat, blood draws and a glucose test to determine insulin resistance, questionnaires about general well-being and eating habits, eating meals and snacks, and an exercise test. * Participants will join one of two group programs at the National Institutes of Health. One group focuses on learning skills to help with bad moods and stress. The other group covers topics that are important for teens to lead a healthy life. The groups will meet for 1 hour once a week for 6 weeks during after-school hours. * At the end of the groups, participants will have three follow-up visits. The first visit will be 6 weeks later, the second will be 6 months after the start of the group program, and the third will be 1 year after the start of the group program. Each visit will take about 6 hours. These visits are similar to the second screening visit before the groups. * Some participants will have extra tests to study stress at the second screening visit and the 6-week, 6-month, and 12-month follow-up visits. Participants will give samples of DNA, saliva to measure stress hormones, and they will take part in a brief stress test. For more information, visit the study website at: http://mir.nichd.nih.gov or contact the research coordinators for the study at 301-594-3198.
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).
The investigators will test the hypothesis that reducing insulin doses using a low carbohydrate diet (LCD) will be associated with with improved insulin sensitivity (Aim 1) and blood vessel health (Aim 2).
The aim of this study is to learn more about how physical activity and cardiorespiratory fitness are related to diabetes risk among breast cancer patients prescribed an endocrine therapy.
The primary purpose of this study is to determine the sex-specific metabolic and molecular response, among adults with prediabetes, when moving from a Western Diet to plant-based diet.
This is a single-center, prospective, randomized, controlled (crossover) clinical study designed to investigate the impact of lowering insulin levels on hepatic glucose production (HGP) vs de novo lipogenesis (DNL) in people with insulin resistance. 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 metabolic dysfunction-associated steatotic liver disease (MASLD). Participants will undergo two pancreatic clamp procedures -- one in which serum insulin levels are maintained near hyperinsulinemic baseline (Maintenance Hyperinsulinemia or "MH" Protocol) and the other in which serum insulin levels are lowered by 50% (Reduction toward Euinsulinemia or "RE" Protocol). In both clamps the investigators will use stable-isotope tracers to monitor hepatic glucose and triglyceride metabolism. The primary outcome will be the impact of steady-state clamp insulinemia on HGP vs DNL.
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
This research study collects health-related information and blood samples to better understand how body composition, lifestyle habits, and diet influence meta-inflammatory monocytes (MiMos) in adolescents. The hypothesis of this study is that adolescents at risk for metabolic disease have enhanced MiMo related activities leading to insulin resistance.
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.