- 2013Pump Priming
Extra-cellular exosomal microRNA – a potential new class of urinary biomarker for diabetic kidney diseaseRecipient:Dr James DearInstitution:University of EdinburghCity:EdinburghAmount:£16,125.00Description: The kidney is often severely damaged by diabetes. Current tests only diagnose kidney problems when a lot of damage has already occurred. We need new tests that identify early damage and tell doctors something about the mechanism of injury. In urine there are particles called exosomes, packets of information released by kidney cells that change when the cells are injured. With DRWF funding we will develop a new method for counting human urinary exosomes and define their cargo. Armed with these crucial pilot data we can go forward and determine what exosomes tell us about diabetic kidney disease.
- 2013Pump Priming
Non-invasive live imaging of immune infiltration into islets of LangerhansRecipient:Professor Anne CookeInstitution:University of CambridgeCity:CambridgeAmount:£19,350.00Description: We are proposing a new way of visualising what happens to the insulin- producing islets of Langerhans when they become the target of an immune response that eventually leads to extensive beta-cell death and insulin dependent (type 1) diabetes. This method will allow us to see not only how immune cells gradually get into the islets, but also how the immune cells respond to various treatments that have been shown to delay diabetes development. It will also allow us to image how the immune system responds to islets grafted from genetically different donors and to grafts containing beta cell precursors differentiated from stem cells.
- 2013Pump Priming
Plasma kisspeptin in pregnancy and gestational diabetes: a translational pilot studyRecipient:Dr James BoweInstitution:King’s College LondonCity:LondonAmount:£19,700.00Description: Gestational diabetes (GDM) is raised blood glucose (sugar) levels occurring for the first time during pregnancy. GDM is associated with increased risk of adverse outcomes for mother and baby. We don’t really know why GDM occurs in some women. During pregnancy the body becomes more resistant to the effects of insulin (the hormone that controls blood glucose levels). During normal pregnancy the mother’s pancreas produces more insulin to compensate and blood glucose remains normal. The increase in insulin production occurs because the insulin-secreting β-cells in the islets of Langerhans in the pancreas both increase in number and release more insulin. GDM occurs when these processes are not enough to overcome the insulin resistance of pregnancy. Kisspeptin is a recently-discovered molecule that is found, along with its receptor, in the placenta and the pancreas. Kisspeptin increases in the blood during normal pregnancy due to massive release from the placenta. The function(s) of kisspeptin in the placenta and the pancreas are unknown. In my research in mice I showed that the kisspeptin receptor, GPR54, is found on β-cells and I demonstrated that kisspeptin increases insulin secretion. My research has suggested that, in pregnant mice, circulating kisspeptin is involved in β-cell responses to pregnancy, supporting islet function. These animal studies continue, but it is now important to examine whether these results translate to humans, as finding a role for kisspeptin in the function of human β-cells may lead to novel therapies for human diabetes. The proposed project is a translational pilot study to see if pregnant women with higher blood glucose levels have lower kisspeptin levels.
- 2012The Professor David Matthews Non-Clinical Fellowship
Identifying Genetic Predictors of Graft Function to Enable Pancreas Transplantation to Become a Lifelong Cure for Type 1 DiabetesRecipient:Dr Matthew SimmondsInstitution:OCDEM, Churchill Hospital, OxfordCity:OxfordAmount:£164,230.00Description: In type 1 diabetes (T1D) the cells within the pancreas, which produce the hormone insulin, are destroyed by the immune system. Injecting insulin is the main form of treatment for T1D patients but in some patients giving insulin does not control their diabetes and they can go on to develop severe problems of the eyes, kidneys, nerves, brain and heart. In these patients, a transplant of the pancreas or the cells from a pancreas is currently the only treatment that can restore the patient’s own ability to produce insulin, as well as improving diabetes related complications. At present 85% of pancreas transplant patients regain normal pancreas function one year after transplantation, enabling them to discontinue insulin use. Transplanted pancreas function can, however, decrease over time and in some patients stop completely, with only 68% of transplant patients having a functional pancreas after five years. Decreased or lack of transplanted pancreas function means a return to insulin and potentially further worsening of other diabetic complications. Currently we cannot predict when the transplanted pancreas will start to fail. I want to test the genetic material obtained from both pancreas transplant donors and recipients, from all pancreas transplant centres across Europe and America, to investigate naturally occurring variations within genes influencing transplant rejection and pancreas development/function to help us try to predict when the transplanted pancreas is likely to fail so that we can administer medicines that might extend the pancreas’ lifespan and the benefits to patients of having a functioning pancreas for as long as possible.
- 2012Sutherland-Earl Clinical Fellowship
The identification of maturity onset diabetes of the young (MODY) and characterization of diabetes subtype in a young multi-ethnic population to inform appropriate treatmentRecipient:Dr Shivani MisraInstitution:Imperial College LondonCity:LondonAmount:£180,000.00 (3 years)Description: Maturity onset diabetes of the young (MODY) is a rare but frequently misdiagnosed form of diabetes requiring expert and tailored treatment. Misdiagnosis results in incorrect management, impacting on health, quality of life and complications. Diagnosis is challenging as MODY phenotypes overlap with commoner forms of diabetes and undertaking routine genetic screening is prohibitively expensive. A MODY probability calculator which uses clinical and biochemical data to predict the likelihood of MODY, has been shown to improve detection of MODY. Those scoring highly are stratified to undergo genetic testing. However, this approach has not been developed, studied or evaluated in South Asians (SAs), where subtype assignment poses a greater challenge due to the higher proportion of young-onset type 2 diabetes.