Active clinical trials for "Insulin Resistance"

The purpose of this study is to test whether anakinra is able to reduce insulin resistance. This will be tested in overweighted type I diabetes mellitus patients, which have no residual beta-cell function. By using this patient group, all positive effects on glycemic control should be the consequence of improved insulin sensitivity.

This project will examine whether short-term (over a 12-hour period) pharmacological lowering of the stress hormone 'cortisol' improves the nervous system response to food intake in overweight or obese individuals who have metabolic syndrome. The investigators know from our previous research that overweight/obese persons who are insulin resistant, have a blunted sympathetic nervous response to carbohydrate ingestion. This means that they are less able to dissipate energy from caloric intake, which would favour the maintenance of the obese state. Cortisol adversely impacts on insulin action and transport into the brain and cortisol levels are often elevated in persons with central (abdominal) obesity. A randomized, double-blind, placebo controlled, cross-over design will be used to compare the effects of overnight treatment with metyrapone (15 mg/kg at midnight and 15 mg/kg at 6 am) versus placebo on sympathetic nervous system activity in response to a standard 75-g oral sugar (glucose) tolerance test. A 2 week washout will separate treatments. Metyrapone is a drug that reversibly inhibits the enzyme 11beta-hydroxylase, and therefore the production of cortisol. It is used clinically to test the activity of the adrenal gland (the key site of cortisol production) and the pituitary gland. The investigators anticipate that at the dosage used, it will lower blood cortisol concentration by 44 to 64% during the experimental morning. The study protocol comprises two screening visits and two experimental mornings. Key procedures will include: Assessment of insulin action (sensitivity) using the gold standard 'clamp' method. Measurement of sympathetic nervous system activity by both biochemical methods (isotope dilution which provides a measure of the apparent rate of release of 'noradrenaline'-the key neurotransmitter in the sympathetic nervous system) and direct intra-neuronal nerve recordings from the peroneal nerve in the lower leg. Indirect calorimetry to assess resting metabolic rate and the response to sugar ingestion. DEXA scan to quantify fat and lean mass. Assessment of arterial elasticity and calf blood flow by non-invasive methods. A standard 75g oral sugar tolerance test. The results will provide important new information regarding the role of cortisol on nervous system function in overweight/obese individuals.

Subjects will be randomized into 4 study groups: 1. Placebo; 2. Anastrazole and Testosterone; 3. Dutasteride and Testosterone; and 4. Testosterone only. A 2 step euglycemic clamp, body composition by dual X-ray absorptiometry scan, hormone and lipid assays will be performed to monitor metabolic effects of each treatment group. We hypothesize that increasing testosterone levels would increase lean mass, decrease fat mass and improve insulin sensitivity. We further hypothesize that improvements in the metabolic profile would decrease with anastrazole and improve with dutasteride, given in conjunction with T administration.

The aim of this study is to further characterize the treatment related changes in insulin sensitivity, substrate metabolism and intra hepatic- and intramyocellular lipid content in patients with hypothyroidism

Obesity is a multinational epidemic. There is evidence that despite educational measures and increased public awareness, the number of obese individuals continues to increase. Of the numerous obesity-related comorbidities, type 2 diabetes remains one of the most significant in terms of mortality and health care costs. Gastric Bypass Surgery (GBS) not only offers an effective form of therapy for morbid obesity, but also amelioration of type 2 diabetes mellitus. The normalization of glucose levels in GBS patients occurs within days after surgery and has been shown in surgical literature to be independent of the weight loss after surgery. The proximal gut, the site of release of certain incretins, may play a role in glucose homeostasis in obese individuals with type 2 diabetes mellitus. One such incretin is GIP, which when released into the circulation during the immediate postprandial period, accentuates the insulin response to a glucose meal. It is hypothesized that overactivity of this enteroinsular axis in obese individuals produces cell resistance to insulin and subsequent type 2 diabetes mellitus. A previous study reported elevated fasting GIP levels, as well as an exaggerated GIP response to a glucose meal, in obese subjects, which was significantly reduced months after GBS following weight loss. This pilot study of obese patients scheduled for GBS will compare the serum levels of certain peptides, including GIP, following a glucose meal before and after GBS, before weight loss has occured. In order to reproduce the preoperative state, and therefore to demonstrate the physiologic change, a small group of subjects who undergo open surgery will undergo the same measurements after surgery, but using a model in which the meal traverses the stomach, duodenum and jejunum with the aid of a gastrostomy tube.

Background: Patients with congestive heart failure (CHF) show muscle mass wasting and decreased testosterone levels. Long-term testosterone supplementation improves walking distance and glucose metabolism of patients CHF. No studies have investigated the integrated effects of testosterone on exercise oxygen uptake muscle strength and glucose metabolism in patients with CHF regardless of the presence of hypogonadism. Aim: To assess the effect of a 12 week testosterone administration on maximal exercise capacity, muscle strength and insulin resistance in elderly CHF patients. Methods: Seventy elderly patients with stable CHF, mean age 71 ± 8 years, ejection fraction 34 ± 1%, NYHA class II/III 38/32, were enrolled. Of these, 35 were randomized to receive testosterone therapy (through intramuscular injection every 6 week) and 35 to receive placebo both on top of maximal medical therapy. At baseline and after 12 weeks all patients underwent echocardiogram, cardiopulmonary test, 6-minute walking test (6MWT), quadriceps maximal isometric and isokinetic strength.

The Metabolic Syndrome (MS) is prevalent in the American population and is strongly associated with premature coronary disease. Lifestyle intervention, primarily exercise and dietary changes, are foundational treatment strategies for independent components of MS, but these interventions have not been thoroughly evaluated in MS. Even with very modest weight loss, in the setting of caloric restriction and exercise, marked improvement MS parameters have been noted. However, it is not known whether it is diet with weight loss or exercise that improves the metabolic derangements associated with MS. We propose a study designed to examine the relative impact of diet or exercise on the components of MS. Furthermore, it is known that psychological factors significantly impact the ability of patients to initiate and sustain lifestyle changes. We will monitor certain psychological states to evaluate their impact on the success of weight loss and sustainability of lifestyle changes throughout this study. Specific Aims: 1.) Evaluate the relative efficacy of diet with weight loss or exercise on improving the markers of metabolic syndrome. 2.) Determine of pre-existing psychological factors influence the effectiveness of diet with weight loss or exercise on the markers of metabolic syndrome. Design: Adult women (> 18 yrs) with a body-mass index (BMI)  30 kg/m2 will be assessed for MS and randomized to one of three groups (n = 34/group), Control (C), diet with weight loss alone (D), or exercise alone (E). The intervention groups will participate in supervised dietary changes designed for weight loss or exercise for 6 months. Anthropomorphic, serologic, and psychological parameters will be monitored and compared using ANOVA. Hypothesis: As indexed by the improvement in the laboratory markers of the components of metabolic syndrome, exercise alone has a more profound positive impact on Metabolic Syndrome then diet with weight loss alone.

Obesity is characterized by continuous low-grade inflammation. This is an important link between obesity and insulin resistance. Results from the investigators' own group of in vitro and in vivo research on mice show that Interleukin-1 is involved in the process of developing insulin resistance. Earlier it has been shown that interleukin-1 receptor antagonist in human subjects improves glycemic control. The investigators' hypothesis is that this is due to improved insulin sensitivity.

The aim of this project is to study the relationship between obstructive sleep apnea (OSA) and metabolic syndrome (MS) in a population of obese patients who are candidates for bariatric surgery. The investigators will study the influence of OSA through hypoxia and sleep fragmentation on different proinflammatory adipokines and cytokines, on metabolic syndrome and on insulin resistance, as well as how these respond to treatment with continuous positive airway pressure (CPAP). In the first part of the study (part A) the investigators will perform an observational study of cases and controls. Based on the diagnostic polysomnography the patients will be divided into two groups depending on their apnea-hypopnea index (AHI): OSA (AHI >= 15/h) and non-OSA (AHI <15/h). The results will be analyzed depending on the presence or not of OSA. In the second part of the study (part B), the patients with severe OSA (AHI ≥ 30/h) will be randomized into two groups: one group will receive CPAP + diet treatment and the other group will only receive diet treatment. After 3 months of treatment (CPAP + diet vs. diet), the investigators will analyze the overall effect on metabolic syndrome and the effect on its individual components, as well as the above-mentioned inflammatory pathways and insulin sensitivity, between the 2 groups. This will be carried out through a randomized controlled study in which the investigators will compare the effect of CPAP with the effect of conservative treatment.

In this project, we propose to recruit lean and obese subjects with different ethnic background (African Americans and Caucasians) to study the alterations of lipid and carbohydrate metabolism and determine whether these disturbances are linked to genetic, inflammatory, oxidative stress, and/or nutritional factors. Because systemic inflammation and insulin resistance are frequent features of obesity, we postulate that an unbalanced diet with high saturated- and low omega 3-fatty acids is linked to obesity-related inflammation and insulin resistance. We propose to investigate fatty acid metabolism and determine the links between fatty acid composition and oxidative stress in tissues of lean and obese subjects. We propose the following aims: Specific Aim 1: Evaluate nutrient intake in lean and obese subjects using the standard NHANES Food Questionnaire. Specific Aim 2: Evaluate the fatty acid composition, including omega-3, in adipose tissue depots, blood monocytes and skeletal muscle, and examine the relationship between omega-3 content and inflammatory and oxidative stress markers. Specific Aim 3: Compare the effects of omega-3 and saturated FA supplementation on inflammatory and oxidative stress markers in vitro in adipose tissue explants, preadipocytes and monocyte culture.