Type 1 diabetes
Diabetes is characterised by a persistently elevated level of glucose in the blood (hyperglycaemia), leading to complications that can be acute and long-term. Acutely, marked hyperglycaemia impairs water and salt balance and energy utilisation, causing thirst, passage of large volumes of urine, dehydration, weight loss and eventually brain dysfunction and coma. Chronically, hyperglycaemia causes degenerative changes in many tissues, especially blood vessels, nerves, the retina of the eye and the kidneys. Diabetes is classified into two major types: type 1 diabetes (T1D, formerly called juvenile-onset or insulin-dependent diabetes) and type 2 diabetes (T2D, formerly called adult-onset or insulin-independent diabetes); T2D accounts for 85% of all diabetes.
Insulin is the central regulator of glucose metabolism and the concentration of glucose in the blood reflects a balance between insulin secretion and insulin action. T1D is due to lack of insulin secretion following destruction of the insulin-producing beta cells in the pancreas beta cells by the body’s immune system. T2D is due to defective insulin action ('insulin resistance') or more correctly to defective glucose utilisation through pathways that are sensitive to insulin. This typology is overly simplistic because insulin resistance contributes to T1D and impaired beta cell function contributes to T2D.
Both types of diabetes have increased steadily in incidence over the last 50 years and now represent a major personal, public health and economic burden. Currently, 150,000 Australians depend on insulin injections every day to stay alive.
Researchers in the diabetes laboratory of the Immunology Division led by Professor Len Harrison have made many advances in understanding the causes of T1D and developing means for its prevention and cure. They pioneered family and community screening for the pre-clinical diagnosis and prediction of T1D, a pre-requisite for prevention trials (www.diabetestrials.org). Having tested a specific vaccine approach and shown that it protected mice from autoimmune diabetes, Professor Harrison then conducted a trial to demonstrate the safety and potential efficacy of this approach in children and young adults at risk. This was the forerunner of the current intranasal insulin trial II (INIT II), a multi-centre prevention trial in Australia and New Zealand involving over 13,000 T1D relatives (www.stopdiabetes.com.au).
INIT II is a major undertaking funded jointly by the National Health and Medical Research Council of Australia and the Juvenile Diabetes Research Foundation (JDRF), New York. Another trial, to determine the effect of the anti-inflammatory steroid, vitamin D3, on the control of diabetes in recently diagnosed patients has been completed. Professor Harrison and Professor Peter Colman from the Royal Melbourne Hospital are the Directors of one of four international TrialNet centers, funded by the National Institutes of Health, USA, and the JDRF, charged with designing and undertaking clinical trials to prevent T1D via a network of 18 collaborative sites in Australia and New Zealand.