- 2019Pump Priming
Towards remission of type 2 diabetes without weight lossRecipient:Dr Nicola GuessInstitution:King’s College LondonCity:LondonAmount:£18,196Description: Significant weight loss (>10kg) can help a large majority of people to come off their medications and achieve remission of their type 2 diabetes. However, for many people, weight loss might not be possible or desired. Promising studies show that low-carbohydrate diets can reduce blood sugar to the level of someone without type 2 diabetes without any weight loss. However, these low-carbohydrate diets also included a lot of high-protein foods. Protein might help the pancreas produce more insulin. Therefore it is not clear whether carbohydrate restriction alone is enough to normalise blood sugar. This study will test the effect of changing the amount of protein in the diet while people are on a low-carbohydrate diet in people with and without type 2 diabetes. We will increase and decrease the protein in random order but keep the carbohydrate intake unchanged to see what happens to blood sugar levels. This will tell us if added protein is specifically needed for carbohydrate restriction to lower blood sugar in people with type 2 diabetes.
- 2019Pump Priming
Uncovering novel, rare genetic causes of type 2 diabetes in people of Bangladeshi and Pakistani heritage participating in East London Genes and HealthRecipient:Dr Sarah FinerInstitution:Blizard Institute, Barts and the London School of Medicine and DentistryCity:LondonAmount:£19,771Description: We aim to investigate new genetic causes of type 2 diabetes (T2D) in people of Bangladeshi and Pakistani heritage, who have been recruited to a community genomics study called East London Genes and Health (ELGH). ELGH is investigating the cause of diseases, e.g. T2D, which disproportionately affect people of this heritage and yet are under-researched, and has involved 30,000 volunteers so far. Preliminary work has identified people with specific, and rare, gene changes that might predispose, or protect, them from T2D. We would now like to invite approximately 100 people with and without these gene changes to participate in more detailed studies to investigate the effect of these gene changes on their health. These studies will include a detailed assessment of their medical and family history, a physical examination and fasting blood sample. Information obtained from these volunteers will be used to perform additional laboratory tests (e.g. measurement of blood glucose, lipid levels, and DNA studies) to investigate if, and how, these gene variants might be linked to disease.
- 2018Pump Priming
A role for hypothalamic hormones in the islet adaptation to pregnancyRecipient:Dr James BoweInstitution:King’s College LondonCity:LondonAmount:£17,782Description: During healthy pregnancy insulin sensitivity in the mother decreases and the insulin-secreting beta-cells in the islets of Langerhans release more insulin and increase in number to maintain normal blood glucose levels. Gestational diabetes mellitus (GDM) is a form of diabetes that occurs specifically during pregnancy and occurs when the maternal islets are unable to sufficiently compensate for the increased insulin resistance, though the mechanisms involved are currently poorly understood. Corticotropin releasing hormone (CRH) and growth hormone releasing hormone (GHRH) are two hormones that are primarily released from the hypothalamic area of the brain. They are responsible for controlling stress responses and growth respectively. Both hormones also have beneficial effects on the beta-cells, though the physiological reason for this is unknown. Levels of CRH and GHRH in the blood are low under most circumstances, but increase greatly during pregnancy due to release from the placenta. Thus, this project will investigate whether CRH and/or GHRH regulate beta-cell adaptation to pregnancy, and whether insufficient CRH or GHRH is linked to GDM.
- 2018Pump Priming
Bringing immunotherapy for type 1 diabetes into the clinic: new windows into the immune responseRecipient:Dr Danijela TatovicInstitution:Cardiff UniversityCity:CardiffAmount:£19,550Description: Type 1 diabetes (T1D) is caused when cells of the immune system called T-cells attack and destroy insulin producing cells in the pancreas. Monitoring of these pivotal immune cells is currently highly challenging as we cannot see what is happening in the pancreas. I have developed ways to monitor T-cell activity by studying organs called lymph nodes that act as ‘stations’on the transport network that T-cells use to travel around the body. These lymph nodes provide a window into what is happening in the pancreas during disease and allow monitoring of events during clinical trials. The technique I developed involves the use of a very fine needle that is guided using ultrasound. I now wish to use it to monitor the T-cells responsible for killing to insulin-producing cells using stateof-the-art technologies developed by my collaborators who are world leading experts in T-cells during T1D. This pump priming funding will allow me to establish important new collaborations aimed at monitoring T-cells during immunotherapy trials.
- 2018Pump Priming
Cx43 mediated regulation of the inflammasome, a therapeutic target in diabetic nephropathyRecipient:Dr Claire HillsInstitution:University of LincolnCity:LincolnAmount:£19,170Description: Cells lining the surface of the small tubes of the kidney work together to ensure that appropriate function is maintained. However, in the diabetic kidney, these cells become bathed in high levels of sugar and associated stress molecules that affect kidney cell behavior. We have previously demonstrated that high sugar reduces stickiness between kidney cells, an event that impairs the way in which cells talk to each other, and ultimately affects their ability to work efficiently. More importantly, our preliminary studies suggest, that in kidneys of people with diabetic nephropathy, there are altered levels of proteins responsible for transferring information between both cells and their surrounding environment. In the absence of appropriate data sharing, cells respond inappropriately to incoming danger changes and ultimately kidney function is impaired. Our proposal aims to understand the mechanisms which link inappropriate cell conversation to the damage that occurs in the diabetic kidney. Importantly, in collaboration with our clinical colleagues, we will demonstrate the ability of a new therapeutic to negate these effects.