ESPE 2014 Highlights: Day One
Opening the morning’s Working Group Session on diabetes technology and therapeutics, Moshe Phillip (Schneider Children's Medical Center of Israel, Petah Tikva) noted that there has been “traditionally little focus on diabetes” at ESPE meetings. Around 50 people were expected for this session, but it was eventually attended by more than 300, which session Chair Tadej Battelino (University Children's Hospital Ljubljana, Slovenia) described as a “big success”.
Technology supporting flexible treatment
Technology has an important role to play in treating patients with Type 1 diabetes, the aim being, according to Phillip, that patients have a “personal electronic physician attached to them”. The session featured three debates in which the overriding theme was that – irrespective of technological advances – treatment should always be flexible and tailored to the individual patient.
In the first debate, Nadia Tubiana-Rufi (Robert Debré University Hospital, Paris, France) and Liat de Vries (Schneider Children's Medical Center of Israel, Petah Tikva) discussed the pros and cons, respectively, of hospitalising children at diabetes diagnosis. Tubiana-Rufi’s institution hospitalises children for an average of 10 days, whereas de Vries reported that the average stay in her centre is just 2.6 days.
Both speakers concluded that there is little difference in glycaemic outcomes between hospital and home treatment. However, Tubiana-Rufi made the point that resources across Europe are highly variable, with the optimal conditions for achieving good patient outcomes most likely to be found in hospital settings.
De Vries highlighted the danger of nosocomial infection during hospitalisation, and also noted that home-based treatment is a lot cheaper and may reduce the impact on the child’s family.
But the consensus, summarised by Battelino, was that the success of hospital- or home-based treatment is partly dependent on the individual child and their family, and should be tailored accordingly.
Battelino provided the pro side of the next debate: whether pumps should be used from the point of diabetes diagnosis. He reviewed evidence showing that pumps provide significantly better glycaemic control than do multiple injections, and concluded that they should be used as long as there is complete team support and sufficient healthcare provider training. His debate opponent, Revital Nimri (Schneider Children's Medical Center of Israel, Petah Tikva), openly admitted than she would rather be arguing for the use of pumps. However, she cited a number of studies showing little difference between pump and injection use within the first few months to a year of diagnosis, and concluded that there is no need to rush to use pumps while the child and their family are still adjusting to the diagnosis. Again, the debaters agreed that the timing of pump use should be guided by individual circumstances.
The final debate, on the benefits of long-acting insulin analogues, also featured an opponent who would rather be arguing in favour; Ragnar Hanas (Uddevalla Hospital, Sweden) admitted that he routinely uses long-acting insulin analogues in his paediatric diabetic patients. However, he noted a number of emerging possible side effects and, in common with debate proponent Carine de Beaufort (Centre Hospitalier de Luxembourg), said that, in any case, insulin pumps are the better option.
Diabetes treatment: near and far horizons
The diabetes theme continued in the day’s plenary lectures, the first of which featured Moshe Phillip discussing the advent of the closed-loop system. Such a system, he said, should reduce hypoglycaemic episodes, blood glucose levels, variability in glycaemic control, and patient burden. This supposition is based on studies of continuous glucose monitoring and glucose pumps – the elements that, along with a closed-loop algorithm, comprise a closed-loop system.
There has recently been what Phillip described as a “new, wonderful wave of publications” trialling prototype closed-loop systems, including a number of reports from the Diabetes Wireless Artificial Pancreas Consortium (DREAM), of which Phillip is a part. The consortium tested an artificial pancreas against a sensor-augmented insulin pump in an overnight hospital-based study, at a diabetes camp and at patients’ home for up to 6 weeks.
The closed-loop system was tested for overnight use, between 23:00 and 07:00, and found to result in better glycaemic control, but a surprising finding was that overnight use had a knock-on effect, with patients also having significantly better glycaemic control during the day.
So Phillip’s concluding remark on the closed-loop system was: “I believe it’s a reality: it’s here to stay.”
In the second plenary lecture, Matthias von Herrath (La Jolla Institute for Allergy and Immunology, USA) looked at the histopathology of Type 1 diabetes, highlighting how many questions remain about the pathogenesis of the condition. Even in the case of MHC1 overexpression – the hallmark feature of Type 1 diabetes – the underlying reasons are unclear.
He highlighted several recent findings, including exocrine infiltration of CD8 cells and the presence of autoreactive CD4 cells in both Type 1 and 2 diabetes, but with autoreactive CD8 being restricted to Type 1 diabetes. He also noted possible cytokine involvement and the lobular pattern of MHC1 overexpression in Type 1 diabetes, with overexpression in the pancreas continuing for around 8 years from diagnosis.
In the long term, he said, these findings suggest a role for combination therapy to maintain tolerance and beta-cell function, and to reset autoreactive cells and suppress inflammation.
Genetic testing centre stage
The afternoon symposia included a session on monogenic diabetes. The first presenter, Katharine Owen (Oxford Centre for Diabetes, Endocrinology & Metabolism, UK), said that about 4% of children with diabetes have a monogenic form, and stressed the importance of diagnosing such cases, because diagnosis can change management. In particular, many children can achieve long-term glycaemic control with sulfonylureas, thereby avoiding insulin injections.
Around 80% of patients with monogenic diabetes initially go unidentified, said Owen, with a 10- to 15-year delay between diabetes and monogenic diabetes diagnoses. She cautioned that, despite the heritability of the disease, family history can be surprisingly uninformative, with parents often diagnosed following their children’s diagnoses. Owen therefore advised that patients with atypical diabetes symptoms should undergo antibody testing, followed by genetic testing.
The theme of genetic testing was continued by Sian Ellard (University of Exeter, UK). Her team has Wellcome Trust funding that allows them to offer free genetic testing for neonatal diabetes, and they receive samples from across the world, helping them to further develop the technique. Their initial approach, using candidate genes, identified mutations in around 66% of patients; now, using exome sequencing of patients and their parents, and in some cases targeted sequencing of noncoding areas, they can identify causative mutations in about 86% of patients.
This represents a shift, said Ellard, from genetic testing to confirm a clinical diagnosis to testing to define the diagnosis and inform treatment. Knowing the causative mutation can guide clinical management, which can range from oral antidiabetic treatment to bone marrow transplant, and predict remission or involvement of other organs.