- 2013Sutherland-Earl Clinical Fellowship
Development of a robust clinically-relevant approach to antibody-medicated diabetes and hypoglycaemiaRecipient:Dr David ChurchInstitution:Cambridge University Hospital NHS Foundation TrustCity:CambridgeAmount:£180,000Description: Two rare and severe disorders of insulin action – namely type B insulin resistance (TB-IR) and insulin autoimmune syndrome (IAS) - are caused by pathogenic antibodies against the insulin receptor (anti-INSR Abs) or insulin (anti-Ins Abs) respectively. TB-IR causes fulminant, acquired insulin resistance, while IAS causes postprandial hyperglycaemia and fasting hypoglycaemia. Each condition may arise in isolation, or may complicate pre-existing diabetes, and may be treated with multimodal immunosuppression. Milder forms of the conditions are often suspected in patients with insulin-treated diabetes and labile glycaemic control, for many of whom subcutaneous insulin infusion therapy is adopted. In this context, a major limitation of current diagnostics is the lack of a clinically accredited diagnostic test for TB-IR in the UK (or the USA), and the qualitative nature of existing anti-Ins Ab testing for IAS, which does not yield useful information about the likelihood that the antibody detected is altering insulin pharmacokinetics, compounded by the inability of most insulin immunoassays to detect analogue insulins. This project thus sets out to develop rapid, robust and quantitative biochemical assays for anti-Ins and anti-INSR Abs that yield clinically useful information, and to incorporate these into integrated clinical/laboratory diagnostic algorithms for brittle diabetes, IAS, severe IR and suspected interference in insulin immunoassay. These investigations will be directly translated into improved patient care, being made available nationally in the NHS via the laboratory supra-regional assay service (SAS) and the National Severe Insulin Resistance service.
- 2013Pump Priming
Evaluating the role of the pancreatic beta-cell in the development of Cystic Fibrosis related diabetesRecipient:Dr Catriona KellyInstitution:Keele UniversityCity:KeeleAmount:£14,600.00Description: People with cystic fibrosis (CF) inherit a genetic defect that significantly shortens life-span. At present, approximately 9,000 people in the UK suffer from CF, and on average, do not live beyond their mid-30s. The genetic defect causes a build-up of thick and sticky secretions (for example, mucus in the lung), which affects the lungs and digestive tracts in particular. In the digestive tract, this causes high blood sugar levels and CF patients often develop diabetes (50% of patients over the age of 30 have diabetes). We do not know the cause, but the development of diabetes accelerates lung disease, which is the primary cause of death among CF patients. This study aims to find out what causes CF-related diabetes (CFRD) by examining the cells which regulate blood sugar levels. The study will not use animal or human tissue, but will create the first artificial CFRD cell model which will be used to study how the genetic defect increases blood sugar levels. This will be the first step in understanding how CFRD develops. By building on this initial investigation, we hope to identify how best to treat these patients to prevent the development of diabetes and increase life-expectancy.
- 2013Pump Priming
Evaluation of a novel glucagon-incretin hybrid peptide for diabetes and obesity therapyRecipient:Dr Victor GaultInstitution:University of UlsterCity:UlsterAmount:£19,975.00Description: The worldwide increase in incidence of T2DM demands development of new drugs which are safe and more effective. Such drugs would also limit the risk of costly long-term complications, which ultimately will have a burden on the NHS. We have recently bioengineered a new drug molecule which acts to stimulate insulin secretion. Our preliminary data also indicate that this drug acts on three key hormones which are important therapeutic targets for treatment of diabetes. We now wish to establish long-term antidiabetic actions of this drug in animal models of T2DM in an attempt to bring forward a new class of agents that offers a safe and exciting therapeutic approach to diabetes-obesity.
- 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.