Active clinical trials for "Insulin Resistance"

Bariatric surgery has been proven to be an effective treatment of type 2 diabetes and it has highlighted to role of the small intestine in glucose homeostasis. Improvement of glucose homeostasis occurs just a few days after the bariatric surgery, where parts of the small intestine is bypassed, has been performed. Furthermore, conditioned medium from the duodenum and the jejunum from both diabetic rodents and humans are able to induce insulin resistance in normal mice and in myocytes. Hence the hypothesis is that the small intestine secretes factors that are able to induce insulin resistance. This project aims to study how orally ingested glucose is able to induce insulin resistance and if this response differs in patients with normal glucose tolerance, impaired glucose tolerance and in patients with type 2 diabetes mellitus. To address this question glucose homeostasis will be studied by comparing whole body glucose uptake during a progressively increased oral glucose load with a graded glucose infusion where the blood glucose levels will be kept in the same range as during the oral glucose load in patients with normal glucose tolerance, impaired glucose tolerance and patients with type 2 diabetes mellitus. Previous studied have shown that different metabolites and bile acids could be involved the regulation of glucose homeostasis. Hence, it is possible that the gut regulates metabolites that could be involved in small intestine-induced insulin resistance described above. The aim of this research is to study metabolomics in plasma collected during the oral glucose tolerance test with increasing load of glucose and the graded glucose infusion where plasma glucose level will be held in the same levels as during the oral glucose tolerance test and study the differences in patients with normal glucose tolerance, impaired glucose tolerance and in patients with type 2 diabetes mellitus. The expected results in this study will demonstrate that the gut plays an important role in glucose homeostasis and that this system is dysregulated in type 2 diabetes. More importantly, novel factors derived or regulated from the gut that regulate insulin resistance and glucose tolerance will be identified which could be possible targets for future antidiabetic therapies.

The purpose of the study is to compare the effects of nesiritide to placebo administered by a continuous IV infusion over 48 hours for the treatment of insulin resistance in healthy, obese, insulin resistant individuals.

Nine healthy, moderately fit male volunteers participated in the study. The subjects gave written informed consent after having been informed of any possible risk and discomfort associated with the study. The study was approved by the regional ethics committee in Denmark (Journal number: H-4-2013-071) and performed in accordance with the Declarations of Helsinki II. All subjects underwent 3 clinical investigations (day 1, day 2 and day 5) during a 5 day glycogen supercompensation regime. The subjects were asked to refrain from physical activity and to eat a controlled diet containing 60% carbohydrates (CHO) for 4 days prior to the initial experiments. Upon arrival at the laboratory on day 1, the subjects performed one-legged knee extensor exercise for 1 hour at 80% of PWL interspersed by 5 min bouts at 90% of PWL. This was followed by interval exercise until exhaustion containing 4 min bouts starting at 100% PWL followed by 1 min at 50% of PWL. Upon cessation of exercise the subjects showered and rested in the supine position for 4 hours. Then a 120 min hyperinsulinemic euglycemic clamp was initiated by a bolus insulin injection (9.0 mU/kg, Actrapid, Novo Nordisk, Denmark) followed by continuous insulin infusion (1.42 mU/kg/min insulin) reaching a level of plasma insulin around 100 µU/mL (n=9). At least 2 hours before the insulin clamp, catheters were placed in both femoral, one antecubital and one dorsal hand vein. A heat pad was placed around the lower part of the arm and hand in order to "arterialize" blood drawn from the hand vein. Substrate uptake/release across the legs was calculated by multiplying the arterial-venous (AV) difference in blood substrate concentration by femoral arterial blood flow (measured by ultrasound, Philips DICOM). Blood glucose levels were maintained at the euglycemic predefined target by continuously adjusting the glucose infusion rate (GIR) (20% glucose solution; Fresenius Kabi, Sweden). Concurrent measures of substrate AV differences and blood flow were performed every 20 min. Muscle biopsies from m. vastus lateralis were obtained under local anaesthesia (3-5 ml of Xylocaine, 20 mg/ml.) in the basal- and insulin-stimulated state (120 min) by use of needle biopsy technique. Muscle specimen were frozen within 20 sec in liquid nitrogen and stored at -80°C for further analysis. A new incision was made for every biopsy and spaced 4-5 cm apart. This insulin clamp procedure in combination with basal and insulin stimulated muscle biopsies was repeated in the rested state (without prior exercise) on day 2 and day 5. The subjects arrived in the morning in the overnight fasted state at day 1, day 2 and day 5. During the 5 day supercompensation regime the subjects were provided a predefined isocaloric diet containing 80% carbohydrates, 10% fat and 10% proteins. All food items were handle out to the subjects and compliance of the diet regime was ensured by survey.

Space flight is associated with detrimental changes to the human body, including bone and muscle loss, fluid changes and deconditioning of muscles in the heart and blood vessels. Bed rest experiments, on Earth, are used to study these changes in healthy volunteers, as the disuse of muscles, and impact on the body, mimic the changes seen in the low-gravity environment of Space. Moreover, these changes are similar to those reported in people who remain in bed for long periods of time, such as is seen in intensive care or stroke patients, and bed rest studies also allow the physiological and biochemical impacts of this confinement to be investigated. For example, we know from previous research that muscle inactivity can lead to the development of resistance to the action of the hormone 'insulin', which is a longer term risk factor for the development of type 2 diabetes. Previous studies suggest that this inactivity-induced insulin resistance occurs within the first 48 hours of immobilization. However, it is not clear whether the biochemical and physiological processes underlying these short-term responses to inactivity are the same as those seen in the longer term. The current study aims to investigate the biochemical and physiological changes seen after 3 days of bed rest and to compare to those measured in a previous 57 days bed rest study carried out at Institut Médecine Physiologie Spatiale (MEDES; Toulouse, France). A 3-day period of reconditioning will subsequently be used to determine if these changes can be readily reversed.

Alzheimer's disease (AD) and other forms of dementia are rapidly increasing with the aging of the population, and show a clear preponderance among people with insulin resistance. Metformin, an insulin sensitizer, is being examined in clinical trials as an anti-aging drug. However, very little objective data is available regarding metformin's effect on the brain, a major organ affected by aging.

The purpose of this project is to investigate the effect of breaking prolonged sitting on acute adipose tissue and metabolic responses.

Recent research has suggested that intranasally administered insulin can reach the brain quickly without passing through circulation and evoke increased insulin sensitivity and tissue glucose consumption during insulin stimulation (low-dose hyperinsulinemic, euglycemic clamp). It is still not known what mechanism causes these changes or what tissues are involved in this. In this study, the changes in tissue-specific insulin sensitivity and glucose uptake will be investigated by using glucose-analogue radiotracer ([18F]-fluorodeoxyglucose) with positron emission tomography (PET) imaging during insulin stimulation. Ten healthy males are studied, each receiving nasal sprays containing insulin or placebo in a randomized order on two separate days. After spray administration, glucose uptake in skeletal muscle, liver, subcutaneous and visceral adipose tissue, myocardium, intestines, brown adipose tissue and brain assessed by PET imaging and glucose uptake in these tissues is analyzed. Endogenous glucose production is calculated facilitating the measurements glucose and radiotracer uptake in tissues and tracer loss into urine. As skeletal muscle consumes most of the glucose available, it is likely that administration of insulin sprays will result in an increased uptake in this tissue. Some increase in glucose uptake might also be seen in other tissue types after insulin spray versus placebo spray administration.

The study investigators hypothesize (1) that the SCFA/acetate metabolism differs between metabolic phenotypes and (2) that using a mixture of fibres that differ in degree of polymerization and branching namely a resistant starch and a human-like milk oligosaccharide enhance the acetate availability in the distal colon and systemic circulation, consequently leading to its metabolic effects. To study this, the investigators will supplement lean, normoglycaemic vs. overweight/obese, prediabetic men with the fibre mixture the day before the clinical investigation day (CID) and study during the CID its effects on fasting and postprandial substrate and energy metabolism.

Counting Carbohydrates (CC) is the preferable method used to calculate the amount of insulin needed for a meal. This method is employed by patients with type 1 diabetes melitus (T1DM). the patients receive the general arithmetic calculation of how much insulin to inject for 15 grams/1 portion of carbohydrate (carb to insulin ratio (C:I) and insulin sensitivity (IS). However, Diabetes Educators are often confronted with difficulties guiding their T1DM patient when using this method and find patients get confused calculating the amount of carbs needed. The investigators sought to create a simple tool that would help our patients implement the CC method easily and properly.

The objective of the study is to identify biomarkers for acute intake of beer and alcohol in individuals with a high or low habitual intake. Furthermore, we wish to identify compounds and metabolites in different types of beer and alcohol, which can serve as compliance markers for intake under the test conditions (blood tests and urine samples). We also wish to determine the acute effects of these beverages on plasma glucose and insulin response, compared to regular soda.