Active clinical trials for "Insulin Resistance"

For a long time, no direct connection was seen between the two common diseases diabetes mellitus and osteoporosis. However, as more and more younger people are affected by obesity, develop type 2 diabetes mellitus and suffer osteoporotic fractures, the question of a connection between these clinical pictures has now arisen. Modern magnetic resonance imaging and spectroscopy techniques allow detailed and non-invasive characterization of bone marrow in different body regions. Low body weight (BMI<20kg/m²) has been shown to be associated with decreased bone density, while obesity has long been associated with high cortical bone mass - the idea of bone health. It has now been proven that obesity also has a negative effect on bone structure. Here, it is not only BMI that is crucial, but also the localization of fat tissue in the body. Visceral fat has a directly damaging effect on bone microarchitecture through dysregulated production and release of cytokines and adipokines. Thus, it has been shown that both type 1 and type 2 diabetic patients have a decreased rate of bone remodeling and very obese patients with type 2 diabetes have an increased risk of fracture. It must be concluded that body weight, or BMI, cannot be the sole measure for estimating bone health. Thus, type 2 diabetes shows reduced bone remodeling with normal or slightly increased bone density, but inferior stability. This means that type 2 diabetes is associated with an increased risk of osteoporotic fracture, even when bone density measurements are unremarkable. Loss of trabecular bone structure in red (hematopoietic) bone marrow is also characterized by increasing infiltration of the bone marrow space with fat cells (bone marrow adipose tissue). In contrast, the yellow bone marrow, which is mainly present in the diaphysis of tabular bones, has particularly large amounts of fat incorporated into the reticulum cells. For a long time, only the role of "placeholder" was attributed to these fat cells, but it has been shown that they interact with other cells via the production of autocrine, paracrine and endocrine hormones and cytokines, or adipokines, and are thus related to the metabolic state of the entire body. A basic assumption here is that the amount of unsaturated fatty acids in the adipose bone marrow is an important and functional marker for different types of adipocytes. It has been shown that 3 individuals with poorer insulin sensitivity have more unsaturated fatty acids in yellow bone marrow. Thus, the concept of different types of adipocytes in the bone marrow, with their inherent different fatty acid composition could serve to reconcile the at first glance counterintuitive physiological regulation of bone marrow fat and its response to metabolic perturbations. In order to show whether and how the composition of the yellow (unsaturated fatty acids) and red (bone marrow adipose tissue) bone marrow differs in healthy individuals, individuals with impaired insulin sensitivity in different age groups and patients with type 2 diabetes, and whether this can be used to detect early changes in the bone matrix with regard to bone density, the proportion of bone marrow adipose tissue in the red bone marrow at different locations in the skeleton will be quantified by means of chemical-shift-selective MRI sequences as well as the composition of bone marrow fat in the yellow bone marrow with regard to the proportions of monounsaturated and polyunsaturated fatty acids by means of volume-selective MRS. A total of 96 healthy volunteers (48 each male and female) aged 25 to 75 years and with body mass index between 18.5 and 35 kg/m² will be included. In addition, 24 patients (12female/12male) with type 2 diabetes will be recruited. After magnetic resonance examination, anthropometric and metabolic characterization (oral glucose tolerance test) will take place.

The study investigates the role of mTOR in mediating enhancement of muscle insulin sensitivity following a single bout of exercise. This will be investigated in young healthy male subjects by administering the pharmacological mTOR inhibitor Rapamycin in a crossover blinded experimental setup known to enhance muscle insulin sensitivity following one-legged knee-extensor exercise.

Muscle atrophy and insulin resistance are common after bed rest in healthy older adults. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistance adults though the mechanisms are not fully known. Metformin used as a preventive strategy to maintain muscle and metabolic health in bed ridden older adults has not been investigated.

This study will be conducted to investigate the Effect of whole-body vibration on insulin resistance in obese postmenopausal women

The Offspring Born to Mothers with Polycystic Ovary Syndrome in Guangzhou Cohort study (PCOS-BIG) was established to investigate the short- and long-term effects of intrauterine exposure to maternal PCOS on the health of offspring in Guangzhou, China. Data are collected regarding maternal PCOS subtypes, nursing, diet and education as well as health outcomes in their later life. Biological samples including blood and tissue samples are also collected from participants.

The investigators propose to deliver a 4-week sleep extension intervention to adolescents to evaluate feasibility of the protocol and obtain preliminary data on intra-individual changes in metabolic parameters induced by sleep extension.

In the absence of excessive alcohol consumption, increased levels of fat in the liver (>5%) are diagnosed as non-alcoholic fatty liver (NAFL). It has been shown that NAFL is strongly associated with impairments in metabolic health such as hepatic and whole-body insulin resistance. Insulin resistance is seen as the earliest hallmark in the development of type 2 diabetes. Insulin has two main effects on the liver: suppressing endogenous glucose production (EGP) and increasing glucose uptake. While the former has been extensively studied and is known to be impaired in NAFL, no studies have yet examined whether insulin-stimulated hepatic glucose uptake is affected by NAFL. Recent methodological developments allow us to visualize and quantify glucose uptake in any given tissue using dynamic Positron Emission Tomography (PET) with 18Fluorinated glucose tracer (FDG) during insulin stimulation. In the present study, we will in a first instance optimize the insulin-stimulated whole-body PET protocol and apply the dose as reported in the literature 4 megabequerels per kg of body weight (MBq/kg) (±8 mSv) in the first three subjects. It will then be evaluated whether the dose can be decreased in the remaining measurements. Another twelve individuals will then undergo the optimized dynamic PET protocol to assess insulin-stimulated hepatic glucose together with whole-body glucose uptake measures. Liver fat content and composition will be assessed by proton magnetic resonance spectroscopy (1H-MRS). Fasted De Novo Lipogenesis (DNL) will also be measured by deuterated water. Additionally, a two-step clamp will be performed to measure whole-body insulin sensitivity and insulin-stimulated suppression of EGP. The identification of the contributing factors to insulin resistance during the development of NAFL is crucial in order to develop more effective strategies for the prevention and treatment of metabolic disorders.

The overall purpose of the study is to investigate whether three weeks of intermittent fasting (alternate-day fasting, (ADF)) result in a more pronounced "metabolic shift" towards the use of ketone bodies than three weeks of Western diet. The investigators will use state-of-the-art PET/CT tracer techniques and well-established steady state kinetics methods for glucose and fatty acids. The study results will provide new insights into the physiological basis of the potential cardio-protective effects of ketone bodies during ADF and will determine whether ADF can help prevent and treat heart failure. Ketone bodies are produced in the liver as an alternative fuel when blood glucose levels are low, as can be seen with various types of diets or after strenuous exercise. The energy produced by breaking down ketone bodies has been shown to require less oxygen than breaking down glucose and fatty acids. In a previous study, the investigators observed that ketone bodies act as a kind of "super fuel" for the heart and improve the heart's energy utilization. It is still unknown how high ketone levels are needed to see these cardio-protective effects. As patients with insulin resistance and/or heart failure have a lower glucose uptake in cardiac tissue, and as energy production by the breakdown of fatty acids is oxygen-demanding, an elevated level of blood ketones can therefore potentially reduce the morbidity seen in patients with type 2 diabetes and ischemic heart disease. PET/CT is a non-invasive well-established imaging modality suitable for tracking the fate of metabolites, as most substances or metabolites can be labeled by a suitable PET isotope. PET has sufficient spatial and temporal resolution to enable direct quantification of e.g. uptake and oxidation rates and has been successfully used by the investigators' department to assess heart efficiency, oxygen consumption, and fatty acid metabolism. Currently, the investigators are in the process of validating the PET tracer 11C-beta-hydroxybutyrate (11C-3-OHB) as a radio tracer for human studies. The tracer will be able to detect changes in biodistribution and kinetics of ketone bodies during both Western diets and ADF. The subjects must go through two study periods of each 3 weeks in which the intervention is western diet (no restrictions) and intermittent fasting (fasting every other day), respectively. After both study periods, there will be an examination day with PET scans and various laboratory examinations.

This study plans to learn more about differences in heart disease risk after gender-affirming orchiectomy (i.e., testes removal) in older transgender (trans) women compared to younger trans women.

This observational study will evaluate the effect of puberty suppression on insulin sensitivity, metabolic rate and vascular health among transgender female youth at baseline and 6 months after initiation of a gondoatropin releasing hormone agonist compared to matched cisgender male controls.