It is well known that Type 1 diabetes is the result of a malfunction in which the insulin producing pancreas cells (called beta cells) are attacked and destroyed by the immune system. Once enough beta cells have been destroyed the pancreas can no longer produce enough insulin and the blood sugar begins to rise. At this stage symptoms of diabetes - thirst, frequent need to pass urine and weight loss - occur. At the time of diagnosis and even prior to diagnosis, antibodies (proteins in the blood which are usually made to fight infections) directed to the beta cells can be detected in the blood.
This process which causes type 1 diabetes is called 'autoimmunity'. This is a fancy name describing a condition in which the immune system attacks a normal body part, in this case the insulin producing cells in the pancreas. Why does this happen? Over many years it has become clear that one of the major reasons is a strong 'genetic risk' for type 1 diabetes. It has been observed that type 1 diabetes frequently runs in families. For example, if one identical twin develops type 1 diabetes there is a 30-40% risk of the other twin developing diabetes. Similarly, if one member of a family has type 1 diabetes there is a 10 fold higher risk than that of the general population that another member will also develop diabetes. This risk is caused by 'susceptibility genes' - pieces of DNA which somehow define a person's risk for a disease.
What do we already know about the genes associated with type 1 diabetes? Quite a lot really. A statistical association with genes called HLA (short for Human Lymphocyte Allele) and type 1 diabetes was first recognized over 30 years ago and has been greatly refined over time. It is now recognized that genes of the class 2 region of the HLA (known as DR3 and DR4) are strong contributors to the genetic risk probably accounting for 50% of the total genetic risk for type 1 diabetes. Tests for these genes are available and can be used to assist in defining risk for type 1 diabetes within families.
What about the other 50% of the genetic risk? A number of other genes have been suggested as strong candidates. The insulin gene and a gene called CTLA4 are some of the strongest candidates. However, the problem with a lot of the research designed to define the genetic risk has been that it has been done on small numbers of families and has not taken into account differences which occur between different population groups around the world.
How do we solve the problem and crack the genetics of type 1 diabetes? Enter the Type 1 Diabetes Genetics Consortium. This is a collaborative international effort to develop a resource which will allow the identification of genes that increase (or decrease) an individuals risk for type 1 diabetes. The plan is to collect DNA samples from families from multiple ethnic groups worldwide. These samples will be available to scientists who will carry out the necessary genetic analyses. Specifically, the Consortium hopes that families in which two or more siblings (i.e. brothers and sisters) with type 1 diabetes will join the study. The Consortium aims to collect DNA from a total of 2500 such families in order to get a large enough sample to be statistically confident of finding the non-HLA diabetes susceptibility genes. Families can help the Consortium through networks in established in Europe, North America, United Kingdom and the Asia-Pacific, including Australia and New Zealand. All the family members will be evaluated for variables such as age at onset and duration of diabetes. Important information will come from study of siblings who have not developed diabetes within these families. Blood samples taken from families will be used to test for antibodies, and to develop cells which will give a renewable source of DNA.
How can we make sure Australia does its bit? The Australasian network is based at the Royal Melbourne Hospital/Walter and Eliza Hall Institute, headed by Dr Grant Morahan and A/Professor Peter Colman. Amanda Loth, the coordinator of the network, has already involved a number of clinics around Australia and New Zealand and is currently training a number of recruitment clinics throughout Asia, with the sole aim to involve families with type 1 diabetes in this project. So far, the Australasian network has recruited 126 families (including 261 people with type 1 diabetes, 57 brothers and sisters without diabetes and 211 parents). The European network has recruited 302, the North American 201 and the UK network 94 families. So great progress has been made but there is still a long way to go.
The families we hope will help us find diabetes genes are those in which two siblings (i.e. two brothers, two sisters or a brother and sister) have type 1 diabetes. What will be involved in joining the study? We will ask for a blood sample, including one from their parents and brothers and sisters who don't have diabetes. In addition, we would complete a short questionnaire about each participant's health and the family's history of diabetes. Currently, there are Consortium recruitment clinics operating in most states of Australia (see below).
This is an extremely important research effort. We hope that the increase in our knowledge of the genetic risk of type 1 diabetes which results from the Consortium will be another major step towards developing better methods of identifying risk of type 1 diabetes as well as prevention and/or better treatments for type 1 diabetes.
To participate or to obtain more information please call or email your nearest clinic.
