for Adipose Tissue DIabetes VAriants (fATDIVA)
Diabetes MellitusThe adipose (fat) cells under the skin are where individuals store excess fat. The more excess fat they have, the more "strain" they put on these cells which then get bigger and don't work as well as they should. Having some fat under the skin is important. People who have a genetic defect which results in them having almost no fat under their skin have a very high risk of a condition called insulin resistance (where the body does not respond as well to insulin and blood sugar levels rise). This can lead to diabetes and heart disease despite them not being overweight. Scientists have only recently started to understand the importance of fat in insulin resistance and how people unable to store fat very well can have insulin resistance despite not being obese. The investigators have also recently discovered that small changes in a person's genetic code (their body's instruction manual) may also affect their ability to store fat and would like to explore this in more detail. To do this, they will recruit volunteers from the Exeter 10,000 study who gave permission to contact them about further research. The investigators will collect detailed body size measures and blood samples taken before and after a special drink that is high in fat (similar to a thick milk shake), then compare the results between people with and without the particular genetic changes of interest. Knowing more about these genetic changes and how fat cells work could help to improve understanding about why some people develop diabetes and heart disease despite a relatively normal BMI.
Fatty Acid Oxidation Defects and Insulin Sensitivity
Very Long-chain Acyl-CoA Dehydrogenase DeficiencyTrifunctional Protein Deficiency5 moreThe purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to allow insulin to keep blood sugar in the normal range. The investigators want to know if having one of the fatty acid oxidation disorders could have an influence on insulin action. Fatty acid oxidation disorders are genetic disorders that inhibit one of the enzymes that converts fat into energy. The investigators will study both normal healthy people and people with a long-chain fatty acid oxidation disorder.
The Effect of Gemcabene on Insulin Sensitivity in Nondiabetic Subjects
Insulin SensitivityThe purpose of this study is to determine the effect of gemcabene on insulin sensitivity as defined by average glucose disposal rate.
Rediscovering Hydroxychloroquine as a Novel Insulin Sensitizer
Insulin ResistanceCurrent options to treat insulin resistance in diabetes are fairly limited. For this reason, novel treatments would represent a major progress. The generic drug hydroxychloroquine (HCQ) has poorly understood effects on blood sugar metabolism. In this study, the investigators will examine the mechanisms by which this drug affects glucose metabolism and which cells are affected. Findings emanating from this project will help establish whether HCQ may be a viable treatment for disorders of glucose metabolism.
Effects of Liraglutide on Hippocampal Structure and Function in Aging Adults With Prediabetes
Insulin ResistanceDementiaThe purpose of this study is to evaluate the effects of liraglutide on the memory and attention of people with insulin resistance. Liraglutide is a medication that makes the body more sensitive to insulin, and therefore may allow it to manage sugar more effectively. The investigators are looking specifically at a region of the brain that is associated with memory and attention, called the hippocampus, in order to see whether treatment this treatment will change performance on memory and attention tasks. The investigators are also taking an MRI of the brain to see whether there are changes to the size and shape of the hippocampus after treatment. All subjects in this study will be 50-70 years old and have pre- diabetes. Half of all subjects will have a family history of dementia, while the other half will not.
Chronic Effects of Natural and Interesterified Fats Margarine on Insulin Sensitivity and Selected...
OverweightThe investigators hypothesized that there will be a significant difference between the effects of trans-free palm-, interesterified palm- and interesterified soybean oil blend on cardiovascular disease, inflammation, insulin resistance and obesity.
Microvascular Dysfunction and the Development of Whole-body Insulin Resistance
Insulin ResistanceType 2 Diabetes1 moreThis study aims to elucidate the role of the microcirculation in the development of whole body insulin resistance. The investigators hypothesize that impaired insulin signaling in the vasculature is an early phenomenon in the development of whole body insulin resistance. Furthermore, the investigators aim to identify improvement of microvascular function as a potential target in diabetes prevention and treatment.
Bromocriptine and Insulin Sensitivity
Insulin SensitivityIn this study the investigators will examine the effect of dopamine (bromocriptine) on insulin sensitivity in lean and obese subjects. Furthermore, the investigators will examine whether the timing of bromocriptine administration has influence on insulin sensitivity. To do so, the investigators will include lean and obese subjects who will use 2 times 2 weeks bromocriptine. In randomized order, they will use it in the morning or in the evening. The investigators will examine insulin sensitivity by performing a 7-point oral glucose tolerance test. Furthermore, the investigators will examine energy expenditure and subjects will keep track of their eating behaviour in the 3 days before each study visit.
Palmitoleic Isomer Study
Insulin SensitivityTrans-palmitoleic acid (trans-C16:1) is a naturally occurring trans fatty acid present in small quantities in foods, most notably in dairy products. Observational evidence suggests a positive association between trans-C16:1 and insulin sensitivity, and negative association with risk of developing type 2 diabetes mellitus [1-3]. Cis-palmitoleic acid (cis-C16:1) is found naturally in foods and is particularly high in macadamia nuts and oil extracted from the sea buckthorn plant. Animal models suggest that this palmitoleic acid isomer also improves insulin sensitivity and reduces metabolic dysfunction. This pilot dosing study is necessary to inform the design of a larger trial to test the hypothesis that both trans-C16:1 and cis-C16:1 improve insulin resistance but at different doses. Plasma phospholipid fatty acid profiles will be used as the primary outcome measure.
Effect of High-intensity Low-volume Training on Insulin Sensitivity in Type 2 Diabetes
Type 2 DiabetesHigh intensity interval training is applied for several diseases. Hypothesis: High intensity interval training improves insulin sensitivity in patients with type 2 diabetes.