Managing type 1 diabetes in a young child

The incidence rate of type 1 diabetes is on the increase worldwide, and there is a sense that this increase is more pronounced in children under the age of five. A condition often diagnosed in adolescence or childhood, type 1 diabetes poses unique management challenges in the very young, at a stage when both physical and cognitive development take giant leaps. 

Prof Declan Cody, consultant in paediatric endocrinology and diabetes at Our Lady’s Children’s Hospital Crumlin and clinical professor at UCD spoke about managing type 1 diabetes in toddlers and pre-school children at the recent Paediatric Diabetes Conference held in the Crowne Plaza Hotel, Dublin. The conference was organised by Diabetes Ireland.

Prof Cody said that the increase of type 1 diabetes particularly in the younger age group was picked up on over 20 years ago, when researchers in Oxford found an annual increase of 4% in under 15-year-olds, but an increase of 11% in those younger than four years old. Prof Cody referred to several studies showing similar results, with EURODIAB, which followed 17 European diabetes registers between 1989-2003 finding an overall increase of 3.9%, but a higher annual increase in the under 4s of 5.4%.

“EURODIAB predicted from these statistics that there would be a doubling in numbers of new diagnoses of type 1 in children under four up to 2020, and I think we’re actually seeing this right now,” Prof Cody commented, and then referred to the Crumlin Hospital figures where 30-40% of new type 1 cases presenting through the emergency department are aged under five at diagnosis.

So why is it so important to distinguish this group of children when it comes to diagnosis and management of diabetes? According to Prof Cody, disease progression in toddlers is rapid and the onset can be more severe. Toddlers have a higher frequency of diabetic ketoacidosis (DKA) at presentation, up to 80% according to some papers, compared to 30% in other age groups.

“As a consequence of this higher frequency of DKA, we’re also seeing a higher presentation in terms of cerebral oedema in the younger child,” Prof Cody explained.

“Interestingly, we also have a shorter duration of symptoms in advance of presenting to hospital and toddlers also have a lower HbA1c at diagnosis. So again, this suggests a shorter duration of hyperglycaemia in advance of presentation, in keeping with this rapid, sudden, aggressive onset of disease.”

Another indicator of this rapid progression of pancreatic beta cell loss is the higher level of type 1 diabetes antibody titres compared to other age groups.

“Toddlers don’t tend to have the honeymoon phase that can be seen in older age groups. And if they do, it’s a shortened one and they’re often on a higher dose of insulin in the first six months of diagnosis compared with older age groups.”

Growth, development and type 1 diabetes

Prof Cody pointed out that infants and toddlers grow at a very rapid rate. The average child will grow between 25-30cm in its first year of life, and another 12cm in the second. Weight will triple in the first year and by two years of age, a child’s head/brain will be four-fifths of adult size. In addition to this rapid physical growth, pre-school children also experience rapid cognitive development, Prof Cody said.

“For children with type 1 diabetes, the risk factors that can negatively impact on cognitive development include early onset of disease; presenting with moderate to severe DKA; having had an episode of severe hypoglycaemia; and the cumulative hyperglycaemic effects,” he explained.

And while the effects of frequent episodes of hyperglycaemia over time are not major, an analysis over a mean of six years did detect an effect on cognitive development, Prof Cody said.

“Hyperglycaemia and hypoglycaemia can both affect cognitive development. Hyperglycaemia through oxidative stress and glucotoxicity and hypoglycaemia essentially through a lack of fuel, and these can both affect brain growth and cognitive development.”

According to Prof Cody, some recent papers have shown that early onset type 1 diabetes has been associated with a reduction in IQ and in executive functions such as memory and attention, and while the differences are small, it means that optimal glycaemic control from diagnosis onwards is essential to give the best opportunity for children to develop.

Obstacles to optimal treatment

There are both psychological and practical obstacles to achieving optimal glucose control in infants and toddlers. The most immediate obstacle that occurs is that of the psychological stress parents are put under when their child is diagnosed.

Parental perceptions

Parents with very young children being diagnosed with type 1 diabetes have a heightened sense of grief, said Prof Cody.

“These children are more often presenting critically ill, and many parents find it difficult from a psychological perspective to have to constantly inject and test their children.”

He referred to a qualitative study of mums of children with type 1, which showed that not only did the mums report more overall stress for themselves, they also reported that their children showed more internalising behaviour, anxiety and somatic symptoms compared to the control mums.

Another study looked at parental perceptions of caring for toddlers with type 1 diabetes aged between five weeks and 31 months at diagnosis. It looked at three phases, from diagnosis and hospitalisation, to caring for the child at home and finally long-term adaptation.

“There’s a lot of negative emotional responses at diagnosis such as anger, fear, grief, hopelessness and inadequacy, often very much stress- and anxiety-related Coping strategies used by parents to help deal with the diagnosis going forward include being assertive, advocating for the child and hoping for a cure in the future,” Prof Cody said.

When it comes to caring for the child at home, another set of psychological stressors appear.

“Parents feel vulnerable and afraid and express it as a time of survival rather than living; they’re basically exhausted,” Prof Cody explained. 

“Some parents had to give up work and there was a loss of flexibility and loss of former support systems,” he added, pointing out that offers of babysitting by grandparents and siblings can suddenly be withdrawn in the face of diabetes management. 

“It makes it very difficult and stressful for parents to deal with the condition. There’s an extreme loss of flexibility and parents can’t ever really get away from it all.”

However, in the longer-term, despite all the worries and stress parents felt when the child was diagnosed, watching the child grow up and develop normally can be a reassurance to the parents. 

Toddlers and food issues

In the young child diagnosed with type 1 diabetes, a whole range of problems present in relation to food intake and its effect on blood glucose, but general advice is that the food shouldn’t be any different than what you’d give other children.

“In infancy, breast milk or infant formula is a complete food up to six months. If the child is being breastfed, there are some general rules that can be used in terms of the bolus amount to give: breast milk has 7.4g carb/100ml so the bolus can be for 5-7g carb/feed at six months and 15g carb > 9 months. So we can advice parents in relation to that,” Prof Cody explained.

As the child grows older, food refusal comes into the equation, this can become a real issue if the child uses food refusal to get what they want.

“If the child has had its bolus or injection and then refuses food, it can create a lot of rushing-around and stressed parents offer ice-cream or biscuits, etc. I guess the message to give to parents is to keep calm, and to not bribe with treats if the child doesn’t eat. 

“Our advice is essentially that if the child refuses food, but the blood glucose is not low, it may be ok to wait a short time before re-offering a meal. Only ever offer two food choices, and if not eaten, remove within 20-30 minutes without comment,” Prof Cody said.

If the food refusal is a bit more entrenched, Prof Cody said that his multidisciplinary team in Crumlin would organise a joint session with psychology and dietetics together with parents to try and tackle this behaviour. The team would encourage mealtimes to be family-centred, away from TVs and other distractions. 

“If it’s even more entrenched than this, and food refusal continues, occasionally a reduction in insulin may be required,” he added.

Grazing is another problem that tends to occur in toddlers, and if a toddler eats every couple of hours, there’s never really a chance for the blood glucose to set back again. “This tendency to graze is something we try to discourage as much as possible,” Prof Cody said. 

“We try to encourage a regular meal pattern of complex carb-based meals/snacks, because with the grazing we tend to end up with persistent hyperglycaemia and it’s very hard to manage that whatever their insulin regime is,” Prof Cody explained.

Balancing food intake and insulin

According to Prof Cody, some questions by parents come up fairly commonly, such as if the child is on multiple daily injections (MDI) is it ok to give the bolus or injection of insulin after they’ve eaten their food. 

“The arguments used by parents is that they can match the insulin dose to the actual food intake; it allows increased flexibility and controls at mealtimes. But we don’t encourage this at all, because it’s very much about getting the insulin in in advance, and if you give the insulin only after the food, then you’ve missed the spike and the child is often already hyperglycaemic by the time the insulin starts to work.

“However, there are things that you can do depending on whether the child is on MDI or an insulin pump.

“If the child is on MDI, the dose can be split into two, one pre-meal and one during the meal, however, this does mean more injections instead, Prof Cody said.

“If the child is on an insulin pump, we tend to advice parents to consider a dual wave, so that if the child doesn’t eat they can suspend the second part of the bolus.”

Practical injection issues

One of the issues in relation to injections is that caused by movement and potential spillage. Young children may react to the pain associated with injections and move around or away as a consequence. This movement may cause some of the insulin dose to be lost, and as children’s doses at mealtimes are very small, even a drop could be as much as 50% of the particular dose. This is why considering diluting the insulin comes into the picture.

“The basis around diluting insulin is that as insulin comes at a 100 unit strength (U100), if you’re diluting it to U50 or even U25, then the volume is larger and if you lose a couple of drops during injection you’re actually not losing as much a percentage of the actual insulin. The smaller the dose, the bigger the percentage insulin lost per drop.”

Some manufacturers will actually give a product with the insulin to dilute it down, Prof Cody further explained, and in disposable semi-pens, the insulin can be diluted to U20/ml to make ‘deci-pens’  to minimise dribbling and leaking.

“This has been shown to give up to a five-fold improved dose accuracy,” Prof Cody commented.

Similar rules around dilution apply to insulin pump therapy. 

“For infants who are on insulin pump therapy, the boluses can be tiny and even the basal rate can be very small, and if a child has been unwell or their blood glucose is already low, you may end up having to put them on temporary basal reductions. The problem with that is that you may end up causing more problems than you solve, by causing cannula blockage and then hyperglycaemia and ketosis. So in the very young child, you can dilute insulin in the pump with N-saline down to 10U to ensure more stable delivery.”

Hypoglycaemia and toddlers

Hypoglycaemia is the biggest area of concern for parents of young children with type 1 diabetes, and is a cause of significant anxiety for parents who worry about the effects the hypos may have on the child. As younger children are unable to communicate about their hypoglycaemia symptoms, parents have to look out for pallor, temperament, tantrums, all in relation to what the parents perceive as being the child’s normal behaviour.

“Toddlers are unable to come to the parents and say ‘I feel low’ so it’s completely up to the parents to look out for what they perceive as symptoms of hypos,” said Prof Cody.

“Sometimes the child may just be tearful or crying, and it may be that they’ve just had a hypoglycaemic episode.”

Impact of hypoglycaemia

Several studies on the potential cognitive impact of hypoglycaemia on the developing brain have reported similar deficits in perceptual, motor memory and attention tasks in children with a history of severe hypos. Significant differences in children with type 1 diabetes and control children in verbal intelligence and visual-motor co-ordination have also been attributed to hypoglycaemia. 

So how frequent are hypos in young children? A  study in 1999 by Mayo Clinic followed children under the age of nine for two years from diagnosis and found that more than half (55%) of the children under the age of two; almost half (45%) of three- to four-year-olds; and only 13% of five-to nine-year-olds had had a severe hypo. In 80% of the under-two-year-olds, there was no obvious cause for these hypos. When the researchers looked a bit further, they found that within the youngest age-group, nearly a quarter (22%) had had a severe hypo with a seizure, while the rate in 5-9-year-olds was only 2%. 

“So the younger the child, the more severe the hypos. They also found higher HbA1c levels in under-twos, despite the age group also having more hypos,” Prof Cody noted.

Night-time hypoglycaemia

Another problem is that of night-time hypoglycaemia. Prof Cody mentioned a 72-hour study looking at hypoglycaemia in 11 toddlers on continuous glucose monitoring (CGM) which found that nine out of the 11 had one or more nocturnal hypoglycaemic episodes right through the 72-hour study, which varied in length from 10 minutes to 480 minutes, and these were not being picked up by the parents. 

A study in which blinded CGM was used versus home blood glucose monitoring (HBGM) 10 times a day, found that only 32% of the hypos recorded on the CGM (most of which were night-time and unsymptomatic hypos) were detected on HBGM, despite the intensive testing.

“But the most worrying about this is that hypoglycaemic episodes that were not found and not being treated, were associated with relapse hypos within three hours,” he explained.

Fear of hypoglycaemia

Parents are extremely nervous about their young child having a hypoglycaemic episode and as a consequence will let the child run high in terms of blood glucose, particularly before bedtime.

“Parents will accept a much higher blood glucose level and are actually happy that their child is running high through the night because at least they know they will not run a hypo.

“The problem with this is that the child will be exposed to hyperglycaemia, and research is now suggesting that it may be hyperglycaemia rather than hypoglycaemia that is more relevant to negative cognitive development, so this needs to be managed as well as possible.”

Best technology

Every year, technology is advancing in terms of what’s available for the management of type 1 diabetes. A study on the use of CGM in children under the age of four found that despite parents being provided CGM devices free of charge, less than half of the group continued to use the CGM up to six days a week after six months, which is the recommended amount. 

“There was no mean reduction in HbA1c between zero and six months, but it did help with parental satisfaction, reassurance and catching hypos,” said Prof Cody.

“When it comes to the question of what is the best insulin regime, it has to be pump therapy for various reasons,” he said.

Continuous subcutaneous insulin injection (CSII) is the best for toddlers, because small variable boluses can be used to reduce nocturnal hypoglycaemia, boluses can be titrated to be precise for meals and can be divided into sections before, during and after meals. It provides flexibility for families and means less injections.

“We now know how big an impact pump therapy is having on overall management and switching children from MDI to CSII does result in sustained improvements in HbA1c, and this is coming out in quite a number of studies,” said Prof Cody.

At Crumlin Hospital, he said, if a child is two years or younger when it presents with diabetes, they try to put the child on a pump straight from diagnosis

 Current figures in Crumlin show that of toddlers under the age of five (n = 43) 18 are on MDI and 25 on pump therapy. Of those on MDI, mean HbA1c is 69mmol/mol, while for those on a pump it’s 57mmol/mol. 

“Research shows us that HbA1c is lower in children on pump therapy rather than MDI and children on pump therapy are having very few severe hypoglycaemic episodes,” Prof Cody added.

He also briefly mentioned newer technology being developed, such at the semi-closed loop system and pumps with low-glucose suspend.

“There are new pumps coming out all the time and in the next couple of years we’ll be put under pressure to put more children on pumps, particularly the younger ones, because of the ability to suspend insulin and start again and we’ll get more confident with these going forward.”

Final observations

With all the extra considerations and problems to take into account when managing type 1 diabetes in the very young child, Prof Cody asked whether we should accept a higher HbA1c target in younger children. The answer is no. 

“There has been debate about hypoglycaemia before puberty versus hyperglycaemia during puberty, and whether you get fewer complications from the hypoglycaemia pre-puberty,” he said.

The jury is still out on this, he added, with research showing opposing conclusions. 

“So the message essentially is, that we have to aim for as good a blood glucose management as possible (ISPAD guidelines of HbA1c < 58mmol/mol for all age groups), and not assume that we’re allowed to run blood glucose levels higher in the younger children,” he concluded.