Delayed diagnosis of type 1 diabetes in children and young people can result in potentially fatal diabetic ketoacidosis (DKA) setting them on the path of poor control and increased risk of diabetes-related complications in young adult life. The signs of diabetes can be subtle, making early diagnosis challenging. This article explores the vague symptoms of diabetes and how and why we need to ‘think diabetes’ and work with the community to reduce the number of children and young people presenting with DKA.

Type 1 diabetes in children and adolescents has become more common in recent years and Ireland is a high incidence country, in the top 25% for diabetes incidence worldwide.¹ The number of new cases of type 1 in children under 15 years in Ireland has increased substantially from 16.3 cases in 1997 to 27.5 cases per 100,000 in 2008.²

Annually, there are on average 275 new cases of type 1 in those under 15 years. However, despite the increased incidence of type 1 in Ireland, each individual GP/practice may not have seen a newly diagnosed child for many years.

Type 1 diabetes is a multifactorial illness; it is an autoimmune condition where those with a genetic predisposition interact with an environmental agent(s) and autoimmune pancreatic beta cell destruction ensues. There is a significant environmental effect as evidenced by epidemiological studies; however the particular initiating environmental trigger(s) have yet to defined. 

The diagnosis of type 1 diabetes is a bolt out of the blue for many families; similar to other regions, we found only 10% of newly diagnosed Irish children had a history of type 1 in a first-degree relative.³

Over 90% of the pancreas is destroyed before clinical symptoms occur. The history with type 1 diabetes is short, generally two to three weeks.^3,4 In the presence of a co-existing infection, the insulin deficiency becomes more extreme and the duration of symptoms shortens. A significant associated infection such as pneumonia can result in rapid metabolic decompensation and DKA.

The classic presenting symptoms are polyuria, polydipsia, lethargy and weight loss.^3,5,6 Other important symptoms are secondary enuresis. Bed-wetting in the previously toilet-trained child is an important symptom that warrants checking the urine for glucose, as is constipation, particularly in younger non-ambulant children who cannot access increased fluids or articulate their thirst; mood-swings/irritability; increased hunger and persisting weight loss despite increased food intake.  Lokulo-Sodipe et al reported fatigue and weight loss as significantly more frequent presenting symptoms in those under two with DKA at diagnosis.⁶

Subtle symptoms

The symptoms of type 1 can be subtle and easily explained away, particularly for more common conditions – drinking more because it’s hot or because youngsters are playing sport; passing more urine because of a urine infection; thirst or anxiety; secondary enuresis because of being upset with school or a new sibling; abdominal pain as appendicitis/an acute abdomen, etc. 

Increased vigilance for diabetes is needed, particularly in younger children, especially those aged under two years where the symptoms are very vague; constipation or irritability and polyuria/polydipsia are harder to recognise. Adolescents can also be challenging to diagnose due to their increased independence and privacy, particularly relating to toileting.

As the symptoms are subtle, the families may adopt a ‘wait and see’ approach and delay seeking advice for some time. The appraisal interval from onset of symptoms to seeking medical help is often the longest part of the pathway from onset to diagnosis.⁵ Parents often say they delayed attending their GP as  despite the symptoms, their children were perceived as ‘well’.⁷ Others had hoped the symptoms would go away.⁵

Even when families do present to their doctor, approximately one-fifth of children have a delayed diagnosis and are not diagnosed at the initial visit^5,6,8 with some delayed up to two weeks.⁸ Up to 24% of the children had multiple contacts with healthcare professionals prior to diagnosis.⁶

Waiting for additional unnecessary tests was the reason for delayed diagnosis in 43-46%.^6,8 DKA was more frequent in those with delayed diagnosis.^6,8 In a meta-analysis of over 24,000 children, almost 40% who presented with diabetic ketoacidosis had been seen at least once by a doctor before diagnosis.⁴

As type 1 diabetes is not uncommon in Irish children and young people, GPs should ‘think diabetes’. A simple check of blood and urine can help exclude or confirm the diagnosis.  

If you suspect a child has type 1, use a glucometer to check for glucose and blood ketones. Alternatively, the urine can be checked for glycosuria and ketonuria.  If the blood glucose is elevated, immediately refer to your local paediatric hospital ED for further management. Additional investigations are not required. Children with type 1 can deteriorate rapidly into DKA even over a matter of hours. 

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is a life-threatening acute metabolic decompensation due to insulin deficiency and a medical emergency. It is characterised by hyperglycaemia, acidosis and ketonaemia/ketonuria.⁹ The associated clinical signs are dehydration, vomiting, abdominal pain and sighing respirations (Kussmal’s breathing) in association with the background symptoms of diabetes. DKA can be fatal. Even in 2016, cerebral oedema accounts for the majority of deaths. The risk of developing cerebral oedema in new onset diabetes is 11.9/1,000 DKA episodes or 1.2%.¹⁰

Cerebral oedema is associated with a 24% mortality and morbidity in 35% of survivors.¹⁰ Younger children, particularly those under two years, are most vulnerable to DKA and cerebral oedema.⁶

In addition to the immediate health risks of DKA, its management is challenging, requiring meticulous treatment and strict adherence to written DKA protocols for children and adolescents. Treatment is intensive with intravenous fluids, intravenous insulin (not without its dangers) and continuous clinical monitoring with hourly blood testing. This is very stressful and difficult for young children, adolescents and their parents.⁷

It is particularly traumatic when the child may have been perceived as ‘well’ by their parents hours or days previously.  The child in DKA requires stabilisation, which often takes 24-48 hours, before any meaningful education regarding diabetes and its management can occur.  Thus, presentation in DKA extends the period of hospitalisation which itself is difficult for families often juggling other demands such as the care of other children and full-time jobs. Those with hyperglycaemia but not acidosis who are not in DKA at presentation often do not even require intravenous fluids and can commence insulin subcutaneously. Their monitoring is much less intense and less invasive. They and their families are less stressed, diabetes education and training can commence sooner and the duration of hospitalisation is shorter.  They may even avoid hospitalisation and be treated at home, where resources are available.

Increasingly it is being recognised that the presence of DKA at diagnosis has long-term consequences for the newly diagnosed child/adolescent.¹¹ There is an association between the average metabolic control around the time of diagnosis and the metabolic control in future years.¹² Those who had poorer control around the time of diagnosis had increased retinopathy and macroalbuminuria in early adult life.¹² Internationally, there is wide variation in the occurrence of DKA at presentation with type 1, ranging from 16-67%.¹³ A previous Irish national study noted the rate of moderate/severe DKA at clinical onset of type 1 was 25%, similar to the UK.^3,6 This rate is too high. 

Awareness campaign

DKA at type 1 diagnosis is avoidable by earlier detection and prompt intervention. Reducing the incidence of DKA is an important therapeutic target. Internationally, health promotion campaigns, such as the Parma campaign, have aimed to increase awareness of type 1 and its symptoms among healthcare practitioners and the general public, to encourage earlier diagnosis prior to the onset of DKA.¹⁴

The Parma campaign resulted in a reduction in cumulative frequency of DKA from 78% to 12.5%.¹⁴ Similarly, in Australia, a two-year intensive prevention campaign resulted in a 64% reduction in DKA at presentation.¹⁵

Diabetes Ireland in collaboration with the Irish Childhood Diabetes National Register is launching a type 1 diabetes awareness campaign to raise awareness of the symptoms of type 1 in our community, to encourage earlier presentation and reduce the frequency of DKA. It is believed that the campaign will have a significant impact on the wellbeing of those with type 1 diabetes, both in the short-term and for their future.

If you would like information leaflets (see picture) or posters from this campaign to display in your practice/clinic, please contact Diabetes Ireland at www.diabetes.ie

Acknowledgement: The Irish Childhood Diabetes National Register (ICDNR) is generously supported by the National Children’s Hospital Foundation 

References

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2. Roche EF, McKenna A, Ryder K, Brennan A, O’Regan M, Hoey H.  The Incidence of Childhood Type 1 diabetes in Ireland and the National Childhood Diabetes Register, Irish Medical Journal 2014; 107 (9): 278-281
3. Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes.
4. Pediatric Diabetes 2005: 6: 75-78
5. Usher-Smith JA, Thompson MJ, Sharp SJ, Walter FM.  Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ 2011: 343; d4092
6. Usher-Smith JA, Thompson MJ, Zhu H, et al. The pathway to diagnosis of type 1 diabetes in children: a questionnaire study. BMJ Open 2015;5:e006470. doi:10.1136/bmjopen-2014-006470
7. Lokulo-Sodipe K, Moon RJ, Edge JA, Davies JH. Identifying targets to reduce the incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in the UK. Arch Dis Child. 2014 May;99(5):438-42 
8. Rankin D, Harden J,Waugh N, et al. Pathways to diagnosis: a qualitative study of the experiences and emotional reactions of parents of children diagnosed with type 1 diabetes. Pediatric Diabetes 2014: 15: 591-598
9. Sundaram PCB, Day E, Kirk JMW.  Delayed diagnosis in type 1 diabetes mellitus.  Arch Dis Child 2009;94:151-152 
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11. Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001: 85: 16-22
12. Fredheim S, Johannesen J, Johansen A, et al and the Danish Society for Diabetes in Childhood and Adolescence Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels. Diabetologia 2013; 56(5): 995-1003 
13. Samuelsson U, Steineck I, Gubbjornsdottir S. A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in childhood is related to metabolic control, macroalbuminuria, and retinopathy in early adulthood – apilot study using two nation-wide population based quality registries. Pediatric Diabetes 2014; 15: 229-235
14. Usher-Smith JA, Thompson M, Ercole A, Walter FM. Variation between countries in the frequency of ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia 2012; 55: 2878-2894  
15. Vanelli M, Chiari G, Ghizzoni L, et al. Effectiveness of a prevention programme for diabetic ketoacidosis in children. Diabetes Care 1999; 22:7-9
16. King BR, Howard NJ, Verge CF, et al. Population awareness prevents diabetic ketoacidosis in children at their initial presentation with type 1 diabetes. Pediatric Diabetes 2012; 13: 647-65