Type 1 Diabetes

Part I Pathogenesis of Type 1 Diabetes mellitus Genetics factors Role of the HLA region Class I group Class II genes Role of other genes in the HLA region Other T1DM associated genes/ results of the genome-wide screen Insulin gene region CTLA4 gene Others Environmental factors Viral agents, Coxsackie's B viruses Rubella, Mumps Others Role of infection in general -hygiene hypothesis Toxins and other environmental agents Animal models NOD BB rat Transplantation models Part II: Type 1 Diabetes Autoimmune process in humans Predisposition to T1DM autoimmunity Incidence and prevalence of the disease Increase worldwide incidence; Shift of onset of the disease to younger age Interplay of the genetic and environmental factors Geographic distribution (North-South differences) Differences in this interplay in different ethnic population Preclinical phase of the T1DM autoimmunity Onset of autoimmunity Immune cell markers T effector cells T regulatory cells NK and other sets of cellular components Antigen presenting cells and their interactions Interplay between the cellular elements (cell to cell and cytokine and chemokines) Humoral markers ICA Biochemical antibodies Insulin autoantibodies GAD65 autoantibodies IA2 and related autoantibodies Others Preclinical metabolic abnormalities Lost of first phase insulin response First phase insulin response History and importance Age dependency Abnormal postprandial blood sugars Oral Glucose Tolerance test Abnormal fasting blood sugars Current model of the autoimmune process, interplay of cellular, humoral and metabolic changes Clinical phase of the T1DM autoimmunity Clinical presentation at onset of the disease With clinical symptoms Classical presentation Diabetic Ketoacidosis Without clinical symptoms Early diagnosis using OGTT and fasting blood sugars Role of risk assessment screening (DPT-1 and other trials) What is known about the clinical course of this group of patients LADA, a special late onset form of the disease Specific clinical characteristics Specific metabolic characteristics Clinical presentation and course of the disease after onset Honeymoon period Role of insulin therapy in inducing Metabolic effect of insulin Immunological effects of insulin therapy on beta cell preservation Role of early diagnosis without clinical symptoms Time after loss of measurable insulin/C-peptide production Long term follow up of cellular and humoral immune markers Long term follow up of metabolic changes Glucose metabolism Lipid and other metabolic derangements Part III: Clinical management of Type 1 Diabetes Mellitus * Towards near normo-glycaemia * New insulin formulation * Insulin and insulin analogues * Short acting * Long acting * New delivery systems * Subcutaneous Insulin pumps * Other insulin delivery systems * Nasal insulin * Inhaled insulin * Blood sugar monitoring * Glucometers * Blood/fingerstics * Transcutan modalities * Continuous monitoring * Artificial pancreas * Close loop systems of the past, present and future * Short term complications and their prevention and treatment * Hypoglycaemia * Signs and symptoms * Management (special focus on early childhood) * Sequels * Hypoglycemia unawareness * Effect on cognitive functions * Metabolic consequences * Hyperglycaemia / DKA * Sign and symptoms * Management * Sequels * Metabolic derangement in DKA * Long term complication and their prevention and treatment * Micro-vascular complications * Retinopathy * Nephropathy * Neuropathy * Macro- vascular complications * Atherothrombotic macrovascular complications of the cardiovascular system * Interactions and common pathways affecting the entire vasculature Part IV. Road to the Cure: Prevention and intervention * Prevention Trials * Primary * No autoimmunity present but risk for disease is beyond general population level and identifiable * Genetic risk * Other markers for risk for Type 1 diabetes autoimmunity * Nutritional Intervention Trial, NIP (omega 3 fatty acid intervention for babies) * TEDDY--The Environmental Determinants of Diabetes in the Young: an observational clinical trial. * Others * No autoimmunity present and risk at the general population level- future opportunities * Secondary * Autoimmune process started (immune markers detectable) * DPT-1 trial * ENDIT trial * Others * Role of both immune suppression and antigen based approaches in prevention setting * Intervention trials * Newly diagnosed patients with Type 1 diabetes Mellitus * Immunosuppressive approach * Early clinical trials * AZT * Cyclosporin * Others * Recent approaches * TrialNet trials * MMF/DZB * Anti CD20 trial * Anti CD3 trials (ITN and European) * Thymoglobulin * Pros and cons of these and other potential agents in Type 1 diabetes * Antigen based approach * Heat shock protein (Peptor trial) * GAD protein (Dyamid trials) * Insulin based trials (Neurocrine; Orban/ITN trials) * Pros and cons of these and other potential agents in Type 1 diabetes * Long-standing disease * Islet transplantation * Human islets transplantation * Pork and other islet transplantation * Pancreas and pancreas/kidney transplantation * Others * Future directions to manage and stop the autoimmune destruction of the beta cells * Stem cell research * Engineering the human bets cells * Immune cell therapy * Engineering regulatory T cells * Gene therapy