19 August 2019

‘Too early’ to screen all kids for pre-diabetes

Diabetes Paediatrics

Screening all young children for pancreatic b-cell autoantibodies could help in the prevention of type 1 diabetes, according to a paper in the Medical Journal of Australia this week that advocates reframing the disease as initially an asymptomatic autoimmune disorder rather than a metabolic one.

But paediatric endocrinologist Professor Jerry Wales says until there is a well-established intervention to prevent its progression, screening will not be acceptable at the general population level.

The paper says most children who develop clinical type 1 diabetes have by the age of five autoantibodies to at least two of four islet antigens – insulin, glutamic acid decarboxylase 65, insulinoma antigen 2 and zinc transporter 8. These autoantibodies, which can now be detected with high accuracy, constitute stage 1 type 1 diabetes, or what the authors call autoimmune b-cell disorder (ABCD).

They say early detection of ABCD would minimise presentations of diabetic ketoacidosis and allow earlier treatment that might preserve pancreatic function for longer. Screening of pre-school children has already been trialled in Europe.

The paper acknowledges that there are no proven means to prevent T1D, but says antithymocyte globulin and various monoclonal antibodies are showing promise.

Professor Wales, director of Endocrinology & Diabetes at the Queensland Children’s Hospital and chair of the diabetes subcommittee of the Australian Paediatric Endocrine Group, said it was well known that the pre-clinical stage of T1D began years before symptoms and was evident with modern testing.

But for screening to be ethical outside of research studies and among first-degree relatives, a treatment needed to be available, not just imminent.

“When I started looking after kids with diabetes, I used to tell people, ‘there’ll be a prevention or a cure along in the next 10 years’, and that was 30 years ago,” he told The Medical Republic.

“We’re a bit nearer, there are some agents that show a bit of promise, but there’s nothing that you would want to expose anybody to routinely and tell them it will stop them getting diabetes, because nobody has managed that.

“It may well take different drugs for different people tailored to their antibody profile, or indeed a combination of several different drugs to alter the immune system in the antibody-positive children. But we’re not there yet, and there’s no point screening for something if you can’t do something about it.”

He said ketoacidosis was a serious complication – “it can kill children, it can certainly cause significant morbidity and intensive care stays, and clots in your veins and strokes on the most severe end of the spectrum” – and risk-awareness did reduce presentations.

But that was still not a convincing enough argument for general population screening, given the cost and the fact that some would be antibody-positive but not progress to illness. Even targeted screening was at this stage only useful for recruiting for studies.

“What you can do is identify people who are potential recruits for research studies using monoclonal antibodies, and we’ve been doing a study exactly like that here in Brisbane: finding children who are antibody-positive and then offering them early intervention to try to keep their pancreas ticking over.

“All the studies so far show that a subset of patients seem to benefit from early intervention, but never all of them. A couple seem to benefit a lot, the majority don’t see the benefit at all. And it may be that there’s something in the genes or antibody profile or the levels of the antibodies that will predict which ones will respond and which ones won’t.

“In children with leukaemia, they started off with steroids, then they added vincristine, then they added cyclophosphamide, then they added cranial radiation, and every time they added something, more people responded. So I suspect in 10 years’ time there’ll be a similar approach to diabetes. People will be picked up very early on and given a cocktail of different immunomodulators that will either prevent them getting diabetes or allow them to keep some pancreatic function for the future.”

Once a treatment was established, he said, further work would be needed to find the best age at which to screen.

MJA, 19 August