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June 29, 2016

Type 1 diabetes in children

June Shannon examines the reasons why growing numbers of children are developing type 1 diabetes and looks at the Irish situation, which is now being monitored through a national childhood diabetes register.
A disturbing but incredibly important study in a recent copy of the Lancet (2009; 373: 2027–33; published online May 28, 2009 DOI:10.1016/S0140-6736(09)60568-7) has predicted a doubling of new cases of type 1 diabetes mellitus (T1DM) in European children under the age of five by the year 2020. It further revealed that prevalent cases in children younger than 15 will also rise by a massive 70 per cent.

Preliminary results from the first year of the Irish Childhood Diabetes National Register have also predicted a very significant increase in the number of children under 15 with T1DM in the Irish population. Worryingly, experts predict that Ireland is facing an increase of approximately 6 per cent per annum compared to other European countries, which are seeing an increase of between three and four per cent.
The Lancet study (‘Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study’ by Dr Chris Patterson and the EURODIAB Study Group) involved 20 population-based registers in 17 countries and included 29,311 new cases of T1DM diagnosed in children before their 15th birthday between 1989 and 2003.
In Europe, prevalence under age 15 years is predicted to rise from 94,000 in 2005, to 160,000 in 2020.
According to the study, “If present trends continue, doubling of new cases of type 1 diabetes in European children younger than five years is predicted between 2005 and 2020, and prevalent cases younger than 15 years will rise by 70 per cent. Adequate healthcare resources to meet these children’s needs should be made available.”
Speaking to IMT, joint co-ordinator of the EURODIAB study Dr Chris Patterson, Reader in Medical Statistics in the Centre for Public Health at Queen’s University Belfast said that type 2 diabetes was beginning to appear even in adolescence, particularly in overweight children and this tended to ‘make big headlines’.
However, he said that this EURODIAB study highlights the fact that there is a steady increase in T1DM, which he said, was ‘much more relevant’.
“Type 2 may be beginning to appear in childhood but only on a very occasional basis. It won’t make any great impact as far as UK and Ireland children are concerned compared with this quite serious increase in type 1…you could probably count the numbers of children with type 2 diabetes in Northern Ireland on the fingers of one hand.”
Writing a commentary on the study in the same issue of the Lancet, Dana Dabelea, Department of Epidemiology, Colorado School of Public Health, University of Colorado, Denver said that although the reason for this rapid increase in young children is not clear and urgently required more study, the finding was important.
“First, younger age at onset of type 1 diabetes is typically associated with more acute symptoms at presentation, including an increased risk of diabetic ketoacidosis and admission to hospital. Second, the changing disease patterns mean that young people with diabetes will have a longer duration of exposure to an altered metabolic milieu, which substantially increases the risk of chronic microvascular and macrovascular complications.”
According to Dr Patterson, while the predicted doubling of T1DM in the under-fives had made ‘eye-catching headlines’, rates were increasing in all of the three age-groups considered. “At present, under-fives account for only a quarter of cases diagnosed before the age of 15, but in percentage terms, numbers are increasing fastest in this youngest age-group.”
h4. Causation
Researchers are still very much at sea as to what is behind the observed increase in T1DM in our young. Despite a number of hypotheses, the cause of the disease is still unknown.
The study states that the rapid changes over time ‘clearly cannot be attributable to changes in prevalence of susceptibility genes’.
“One suggestion is that the need for genetic susceptibility has lessened over time because of heightened environmental pressure, which results in a raised disease progression rate—especially in individuals with protective HLA genotypes.
“Several hypotheses based on analytical epidemiological studies have pointed to modern lifestyle habits as possible environmental factors, such as increased weight and height development, and Caesarean section deliveries, or reduced frequency of early infections,” the researchers stated.
Dr Patterson and colleagues are currently undertaking a systematic review of the possible environmental risk factors associated with T1DM in children. One of these is Caesarean section delivery at birth.
“There are various risk factors even at birth that have been recognised but they’re all pretty weak…it’s thought that the gut microbial content of a section-delivered baby is different to that of a baby born naturally. It seems that the birth process may have some influence on the microbial content of the infant gut, which is actually rather important in the development of the immune system.” However, the Queens lecturer added that Caesarean delivery seems to relate to only a 20 per cent increase in risk, which he said was very small. Other possible environmental risk factors include older maternal age, high birth-weight or a rapid increase in weight early in life.
h4. Geographical divide
The world can be divided into high- and low-risk regions for incidence of childhood T1DM. Europe is a high-risk region and there is a clear north/south gradient but with some exceptions. More northerly countries tend to have high incidence, with Finland currently having the highest rate of childhood T1DM in the world.
However the rates in Sardinia are almost as high as Finland, which is completely out of keeping with the lower rates in neighbouring countries. The increase in incidence in more westernised cultures may be a reflection of increasing affluence and societal changes.
h4. Irish figures
Although Northern Ireland contributed register data for the EURODIAB collaboration, the Republic of Ireland did not take part as the Irish Childhood Diabetes National Register was only established in January 2008. Thanks to the establishment of the register, Ireland will be participating and collaborating with EURODIAB from now on.
The most robust Irish figures from 1997 showed the Republic to be in the top 25 per cent of disease incidence in Europe for T1DM in children.
According to the 1997 study, which provided a measure of case ascertainment, the incidence of T1DM in children under 15 in the Irish population was 16.3 cases per 100,000 per year, 16.4 in males under 15 and 16.2 in girls under 15.
Dr Edna Roche, Consultant Paediatrician and Consultant in Paediatric Endocrinology at the National Children’s Hospital in AMNCH Tallaght and the Department of Paediatrics at Trinity College Dublin, conducted the 1997 study and established the Republic of Ireland’s first register for childhood diabetes.
She currently runs the national register with research nurse Amanda McKenna.
Dr Roche said that she would very much echo Dr Patterson’s concerns at the accelerated increase of the disease in young children.
Worryingly, preliminary data from the first year of the Irish register reveals a very significant increase in the number of children with T1DM aged under 15 and Dr Roche estimates that Ireland is probably looking at an increase of approximately 6 per cent per annum compared to other countries, which are seeing an increase of between three and four per cent.
She said the importance of tracking these changes over time underlines the value of the Irish Childhood Diabetes National Register, which covers the 26 counties and is generously supported by the National Children’s Hospital in Tallaght.
“The outcomes in terms of diabetes care clearly relate to the resources that are put into it. That can’t happen if you don’t know who has diabetes and who doesn’t. That’s why a register is so important,” Dr Roche stated.
“We’ve had tremendous support from paediatricians, paediatric diabeteologists and endocrinologists nationally in pursuing this work. We’re also collaborating with the EURODIAB network in terms of our role on the international stage. What actually causes type 1 diabetes is so complex that no one country is going to be able to shed any huge light on why that may be. That’s why you need collaboration across many centres,” she added.
h4. Subtle symptoms
The difficulty in diagnosing T1DM in a child under the age of five is that they are unable to articulate any difficulties and can therefore present with very subtle symptoms. This subtlety can also mean that younger children are more likely to present in diabetic ketoacidosis (DKA).
“Classically in the older child, they drink more, go to the toilet more and have weight loss despite a huge increase in appetite. As it proceeds, they may have vomiting and abdominal pain if they’re getting extremely unwell with their diabetes. That’s what we call diabetic ketoacidosis. With some of the younger children, because they’re in nappies, you may not perceive that they’re going to the toilet more. Often you may not perceive that they’re thirstier because they can’t go and get a drink like an older child.
“So the symptoms in the younger child can be much more subtle like constipation. Bedwetting in a child who has previously been toilet trained can sometimes highlight children with diabetes,” Dr Roche explained.
DKA rates at diagnosis vary internationally. Presentation in moderate/severe DKA occurred in 25 per cent in 1997 and in 66 per cent of those aged under two. More recent national data on the frequency of DKA at presentation is not yet available, although it would appear to be decreasing due to the high level of community awareness.
“This shows how good our GPs are at detecting diabetes early,” she said.
h4. Blood-monitoring meters
Depending on their age, children and parents are taught how to use a meter to monitor blood sugars and ketones.
“Diabetes is one of the areas where we can see the superb impact of technology in our ability to deliver care for people. The ability to test with very small portable and reliable meters is much easier. Many years ago, people just checked strips in their urine, which was much slower, so these are much more useful and they’re getting better all the time,” she stated.
h4. More research needed
According to Dr Chris Patterson, the most recent EURODIAB study highlights the need for more research into the causes for the increase of T1DM in children, which he agreed could be described as a ‘time bomb’ in terms of its future impact.
“Potentially an environmental risk factor, if it could be identified, could offer a very quick solution but there’s a very big ‘if’ there. It might be a whole host of factors rather than one specific thing.”
Coupled with the distress to the patient of having a life-long chronic condition, Dr Patterson also highlighted the fact that diabetes is an incredibly expensive disease, which costs the health service a substantial amount of money every year.
Many procedures on diabetic patients are more expensive and often involve a longer hospital stay. These are the hidden costs, which need to be added to the more obvious costs of insulin, medication, monitoring and treating diabetic complications, he said.