PracticeUpdate: Conference Series | ADC 2018

Preventing Type 1 Diabetes: What We Know INTERVIEW WITH JOHN WENTWORTH MBBS, PhD, FRACP

A lot of work has gone into looking at ways to prevent close relatives of people with type 1 diabetes (T1D) from developing the disease, and to stop or slow progression in those who are in the early stages of T1D. The presence of islet autoantibodies – for example, GAD, IA-2, zinc trans- porter 8, and insulin – tell us that the immune system is activated and is attacking the pancreas. These autoantibodies are present, often for years, before T1D develops. Close relatives of a person with T1D have a 15-fold increased risk of devel- oping diabetes themselves. Approximately 1 in 40 will have two or more islet autoantibodies and will eventually progress to T1D at some stage in their life. By screening close relatives of people with T1D for these autoantibodies, we can pick out those most at risk of developing the disease. However, such targeted screening only picks up the 15% to 20% of people in the community who will eventually develop T1D. We are not capturing the other group of people who don’t have a first-degree relative with T1D but who end up getting diabetes anyway.

Dr. Wentworth is an Endocrinologist at the Royal Melbourne Hospital and Clinician Scientist at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

Dr. John Wentworth

" These findings raise the possibility that maybe immune therapy is best used just before a person develops T1D… "

For these reasons, there are arguments supporting blanket screening of the population to identify those at risk of developing diabetes. The justification is twofold: if we know a person is at risk, we can be alert to the signs of pro- gression and treat him or her before that person falls critically ill with high sugars and ketoacidosis; secondly, we may be able to stop someone at risk from getting T1D or at least slow the progression to diabetes.

Can immune therapy and insulin prevent T1D progression? Several immune therapies are currently being trialled for preventing or delaying the progression of T1D. These include abatacept, tocilizumab and anti-thymocyte globulin (ATG). We know that these drugs are effective against autoimmune disorders, but they can also cause problems; for example, with cytokine storm. The worry is that they are going to be too toxic for routine use in T1D, at least in the sorts of doses that are currently being used to treat other autoimmune disorders. The insulin vaccine approach, which Leonard Harrison and I presented on at this meeting, is a relatively safe way to go about preventing T1D. ( See pages 6 and 7. ) Both, the oral and intranasal, insulin approaches seem to be effective in mouse studies. However, in humans, there has been no clear benefit to people who took it – although, in the case of oral insulin, children who were very close to their diagnosis appear to be protected from progressing to T1D with oral insulin – delaying T1D diagnosis by about 2 years. These high-risk children are the ones with low first-phase insulin release and relatively low pancreas function. Leonard Harrison’s study, which had children with normal pancreas function and who had relatively early-stage T1D, found no benefit of intranasal insulin in delaying progression to T1D. These findings raise the possibility that maybe immune therapy is best used just before a person develops T1D, although that still needs to be proven in follow-up clinical studies. If that is the case, we'll need to work out how to identify antibody-positive people who are nearing the end of the preclinical disease phase and treat them to prevent progression to diabetes and insulin dependency. This is one of my research interests now. www.practiceupdate.com/c/73012

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PRACTICEUPDATE CONFERENCE SERIES • ADC 2018