T1D is an autoimmune disease in which the insulin-producing cells in the islets of Langerhans are destroyed by a specific immune-mediated mechanism. The disease is characterised by an absolute deficiency for insulin, and patients depend on daily injections of insulin for survival. Preservation of some residual beta cell function in T1D was shown to have substantial clinical benefits for the patient in terms of reduced short and long-term diabetic complications. A possible cure for T1D could be achieved by restoring the functional beta cell mass by activating beta cell regeneration in a controlled manner. Our efforts will focus on two areas of T1D research in which Danish investigators have a long tradition and extensive experience. We will take advantage of the unique Danish Childhood Diabetes Registry for identifying factors associated with beta cell function in T1D. In addition, efforts will be made in order to identify and characterise factors capable of stimulating beta cell growth and inhibiting apoptosis using animal models of T1D and in vitro systems. Experimental new technologies will be used in order to replace damaged beta cells by stem cell-derived insulin-producing cells. The approaches will, in a complimentary fashion, address the possibility of both preserving, restoring and replacing (stem cells) beta cell mass.
T2D is caused by a complex interplay between genetic and environmental factors, the latter being evidenced by a decreasing age of onset under the influence of Western lifestyle factors such as physical inactivity and increased caloric intake. T2D is characterised by IRin major metabolic tissues such as skeletal muscle, liver and adipose tissue and failure ofthe pancreatic beta cells to compensate for this abnormality. Recent evidence also suggests a role for gut-derived hormones and low-grade-inflammation in the development of T2D. A better understanding of the complex pathogenesis of IR and beta cell failure is therefore of major importance to improve preventive and therapeutic strategies. The major areas of interest for the Academy will be to further characterize the molecular mechanisms of IR in skeletal muscle and adipose tissue including the role of adipokines and myokines mediating cross-talking between these tissues, and the possibility to increase energy expenditure by turning white adipocytes into brown-like adipocytes. Moreover, the mechanisms by which physical activity improves insulin sensitivity in high-risk individuals and patients with T2D will be studied. Efforts will also be made to understand how nutrient overload causes beta cell dysfunction and the role of the small intestine and gut incretin hormones in T2D pathophysiology. This is expected to provide novel targets for a more specific treatment of IR, beta cell dysfunction and low-grade inflammation, and thus provide better options for the prevention and treatment of T2D and its complications.
Diabetes in pregnancy (both T1D and T2D), and to a lesser extent GDM and obesity, are associated with increased rates of maternal and fetal complications, and evidence clearly shows optimized metabolic control during all trimesters of pregnancy to significantly reduce the risk of these complications. Recent reports indicate intrauterine hyperglycaemia to dramatically increase the risk of diabetes, overweight, the metabolic syndrome and cardiovascular disease in the offspring. We will take advantage of a well-established collaboration between Danish Centres for Diabetes and Pregnancy to examine the long term consequences of a diabetic intrauterine environment in large cohorts of offspring of women with T1D. In selected subgroups, we will study the specific molecular signature of intrauterine exposure to hyperglycaemia in human tissues and blood, including the role of epigenetics and transcriptional changes. The new international criteria for diagnosis, potential biomarkers for complications as well as effects of different treatment regimens in women with GDM will be evaluated. Finally, we will examine the effect of lifestyle interventions in obese pregnant women and their offspring.
Having diabetes puts patients at increased risk of premature cardiovascular disease and for developing micro- and macrovascular complications including retinopathy and nephropathy. Although progress has been made in predicting and preventing diabetic complications, the overall mortality among diabetic patients in Denmark is around 60 % greater than in the background population. Clinical progress into this area is hampered by a lack of tools to detect early markers of many diabetic complications and by inadequate tools to treat diabetic complications when identified. Major areas of interest for the Academy will therefore be to develop new diagnostic tools to identify diabetic patients at high risk of complications and to prevent and treat complications using individualized treatment regimes.
Suboptimal diabetes control is a major cause of early development of diabetic complications. To obtain tight glycaemic control without hypoglycaemia throughout a diabetes life is very difficult and almost impossible for most patients with the currently available tools. Over the past decades medical technologies have developed rapidly and sensor technologies are now available for a number of tasks. A few examples are CGMS and smart “insulin pumps” (continuous subcutaneous insulin (CSII)) with the possibility to get bolus calculation advices. The JDRF artificial pancreas project already shows promising results on this topic. Moreover, telemedicine to secure patient treatment at a distance is being introduced in close collaboration with a number of sensor technologies. Our efforts will focus on developing a closed loop system for insulin delivery, to optimize the patients’ and health care providers’ use of current technologies for support in diabetes treatment decisions, to design and develop new technologies for treatment support purposes and to develop information technology (telemedicine).