Ireland is in the top 25% for diabetes incidence worldwide.¹ The number of new cases in children under 15 years in Ireland has increased substantially from 16.3 cases/100,000/year in 1997² to
27.1 cases/100,000/year in 2018.³ However, our rate of diabetes appears to be stabilising, albeit at a high incidence rate.^3,4 Annually there are on average 285 new cases of type 1 diabetes diagnosed in those under 15 years. 

The symptoms of type 1 diabetes can be subtle and vague and thus we need to ‘think diabetes’ and work with our community to reduce the number of children and young people presenting with diabetic ketoacidosis (DKA). The acronym ‘TEST’ is a reminder of the key diabetes symptoms:

T – increased thirst

E – energy depleted

S – sudden weight change (weight loss)

T – toilet trips increased.

It can be difficult to recognise the classic symptoms of polyuria and polydipsia in an adolescent due to their increased independence and privacy, particularly relating to toileting. Children under two years are particularly vulnerable to delayed diagnosis where the symptoms are increasingly vague, including irritability and constipation. The classic symptoms of polyuria and polydipsia are more difficult for families to recognise until well advanced, with nappies persistently leaking or bursting. 

Delayed diagnosis in childhood diabetes is often due to families waiting to seek help due to the vagueness of the symptoms. The time from parents recognising the onset of symptoms to seeking medical help is the ‘appraisal interval’ and this is often the longest part of the pathway from symptom onset to diagnosis.⁵ Parents report delaying seeking medical help for diabetes symptoms because they hoped the symptoms would go away⁵ and because they perceived their child was ‘well’.⁶

Childhood diabetes due to insulin deficiency is rapidly fatal without insulin therapy. In the early stages the signs of diabetes in young children and teenagers can be subtle, sometimes making early diagnosis challenging. Delayed diagnosis of type 1 diabetes can result in potentially fatal metabolic decompensation or DKA. In addition to its immediate risks, there is increasing evidence that the presence of DKA at diagnosis sets children and young people on a path of poor metabolic control and increased risk of diabetes-related complications in young adult life. 

Type 1 diabetes is a multifactorial disease. It is an autoimmune condition where those with a genetic predisposition interact with an environmental agent(s), and autoimmune pancreatic beta cell destruction ensues leading to insulin deficiency.⁷ Despite great advances and much research, the cause is not yet fully understood.

While there is a genetic tendency towards the development and also protective haplotypes, only 10% of newly diagnosed children in Ireland had a history of type 1 diabetes in a first-degree relative; this is similar to other populations.⁸ A diagnosis is a bolt out of the blue for most families.

Type 1 diabetes has a number of stages in its development⁷ and by the time clinical symptoms occur over 90% of the pancreas has been destroyed. The clinical history is short, at two to three weeks.^8,9 If associated with an infection causing insulin resistance, the effects of the insulin deficiency become more extreme and the symptom duration shortens. A co-existing pneumonia or other significant infection can result in rapid metabolic decompensation into life-threatening DKA.

The classic presenting symptoms of type 1 diabetes are polyuria, polydipsia, lethargy and weight loss.^5,8,10 There are other less common but important clues to childhood diabetes which include:

• Secondary enuresis – bed-wetting in the previously toilet-trained child is important and warrants checking the urine for glucose
• Constipation, particularly in non-ambulant children who cannot complain of thirst or access increased fluids
• Irritability or mood swings
• Increased hunger and persisting weight loss despite increased food intake⁸
• Fatigue and weight loss were significantly more frequent symptoms in those aged under two years with DKA at diagnosis.¹⁰

Missed opportunities

In a meta-analysis of over 24,000 children, almost 40% with DKA had been seen at least once by a doctor before diagnosis; these were missed opportunities.⁹ It is important to look out for the subtle symptoms and ‘think diabetes’. A simple check of blood and urine can help exclude or confirm the diagnosis. 

In a child with symptoms suggestive of type 1 diabetes, a glucometer is sufficient to check for glucose and blood ketones. The urine can also be checked for glycosuria and ketonuria. If the blood glucose is elevated or there is glycosuria, the child should be immediately referred to paediatric emergency department for further management. 

A random glucose > 11.1mmol/L in a child with symptoms is enough to suggest a diagnosis of diabetes. No additional investigations are required. Children with type 1 diabetes can deteriorate rapidly into DKA even over a matter of hours, so they should attend hospital the same day without delay. 

As the symptoms tend to be subtle, there is a tendency for the symptoms to be attributed to more common conditions or explained away and minimised. 

The majority of children and young people presenting to their doctors with symptoms of diabetes will be diagnosed that day. However, approximately one-fifth of children are not diagnosed at the initial visit,^5,10,11 with some delayed up to two weeks.¹¹

A study in the UK found that almost a quarter of children had multiple contacts with healthcare professionals prior to diagnosis.¹⁰ In almost half the cases of delayed diagnosis, the reason for the delay was waiting for additional unnecessary tests.^10,11 DKA was more frequent in those where diagnosis was delayed.^10,11

Diabetic ketoacidosis (DKA) – a medical emergency

DKA is a life-threatening acute metabolic decompensation due to insulin deficiency characterised by hyperglycaemia, acidosis and ketonaemia/ketonuria.¹² The clinical signs of DKA (in association with the background symptoms of diabetes) are dehydration, vomiting, abdominal pain and sighing respirations (Kussmaul breathing), which if untreated can progress to coma and death. 

DKA can still be fatal in children even in developed healthcare systems, with a mortality rate of 0.15% to 0.3%.¹³ 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%.¹⁴ Cerebral oedema is associated with a 24% mortality and morbidity in 35% of survivors.¹⁴ Younger children, particularly those under two years, are most vulnerable to DKA and cerebral oedema.¹⁰

The medical management of DKA is challenging, requiring meticulous management and strict adherence to written protocols specific to children and adolescents. The required treatment is intensive with intravenous insulin, fluid and electrolytes. 

Treatment of DKA is not without its dangers. Continuous clinical monitoring with hourly blood testing is required. The treatment and monitoring of DKA is very stressful and frightening for young children, adolescents and their parents.⁶ The trauma is further exacerbated by the sudden onset where the child may have been perceived as ‘well’ by their parents only hours or days previously.

When a child presents with DKA at diabetes diagnosis, a period of stabilisation of 24-48 hours is required before meaningful education regarding diabetes and its management can happen, resulting in a prolonged hospitalisation. 

In contrast, a child or adolescent with a new diagnosis of diabetes who does not have DKA has a very different course. Those diagnosed and referred early who have hyperglycaemia but not acidosis often do not even require intravenous fluids, and can eat and commence insulin subcutaneously.  They do not require ICU or HDU admission; 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. Currently all children and young people with new onset diabetes are admitted to hospital in Ireland to commence treatment. 

There is wide international variation in the occurrence of DKA at diabetes diagnosis in children, ranging from 16-67%.¹⁵ The Irish Childhood Diabetes National Register prospectively monitors the rate of DKA at diagnosis and reported almost one-third (31.6%) of children had DKA at diagnosis in the period 2011 to 2015.¹⁶

More recent data would suggest the rate of DKA at diagnosis in Irish children has exceeded 40%.¹⁷ This rate is too high. DKA at diagnosis is avoidable by earlier detection and prompt intervention. Reducing the incidence of DKA at diagnosis is a vital therapeutic target.

Increasing evidence is emerging of the long-term adverse effects of DKA at diabetes diagnosis for children and adolescents.¹⁸ Cameron et al found evidence of morphological and functional brain changes in children with DKA at diabetes diagnosis.¹⁹ There is an association between the average metabolic control around the time of diagnosis and in future years.^20,21 In addition, those with poorer metabolic control around the time of diagnosis had increased diabetes-related complications of retinopathy and macroalbuminuria in early adult life.²⁰

References 

1. Patterson P, Guariguata L, Dahlquist G, et al. IDF Diabetes Atlas. Diabetes in the young – a global view and worldwide estimates of numbers of children with type 1 diabetes. Diabetes Res Clin Pract 2014;103:161-75
2. Roche EF, McKenna A, Ryder K, Brennan A, O’Regan M, Hoey HMCV. The Incidence of Childhood Type 1 diabetes in Ireland and the National Childhood Diabetes Register, IMJ 2014; 107(9):278-81
3. McKenna A, O’Regan M, Ryder K, Fitzgerald H, Hoey H, Roche EF. Incidence of childhood type 1 diabetes mellitus in Ireland remains high but no longer rising. Acta Paediatrica, 2021, DOI: 10.1111/apa.15836
4. Roche EF, McKenna AM, Ryder KJ, et al. Is the incidence of type 1 diabetes in children and adolescents stabilising? The first 6 years of a National Register. Eur J Pediatr 2016; 175(12):1913-9
5. 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
6. 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: 591-8
7. Couper JJ, Haller MJ, Greenbaum CJ et al. ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. Pediatric Diabetes October 2018; 19(S27):20-7 
8. Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes.
9. Pediatric Diabetes 2005; 6:75-8
10. Usher-Smith JA, Thompson MJ, Sharp SJ et al. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ 2011; 343:d4092
11. 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 
12. Sundaram PCB, Day E, Kirk JMW. Delayed diagnosis in type 1 diabetes mellitus. Arch Dis Child 2009; 94:151-2 
13. Wolfsdorf JI, Glaser N, Agus M et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic Ketoacidosis and the hyperglycaemic hyperosmolar state. Paediatric Diabetes 2018; 19(S27):155-77
14. Decourcey DD, Steil GM, Wypij D, Angus MS. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral oedema in paediatric diabetic ketoacidosis; an 11-year retrospective analysis of mortality. Pediatr Crit Care Med 2013; 14:694-700
15. Edge JA, Hawkins MM, Winter DL et al. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001; 85:16-22
16. Usher-Smith JA, Thompson M, Ercole A et al. Variation between countries in the frequency of ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia 2012; 55:2878-94  
17. Roche E, McKenna A, Ryder K et al. The frequency of diabetic ketoacidosis at type 1 diabetes onset in a national incident cohort over a 5 year period. Pediatric Diabetes 2019; 20(S28):108
18. Roche EF, McKenna AM, O’Regan M et al. The incidence of type 1 diabetes in children under 15 years of age is rising again – a nationwide study. Eur J Pediatr 2023; 182:4615-23
19. Fredheim S 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 
20. Cameron F, Scratch S, Nadeebaum C et al. Neurological Consequences of Diabetic Ketoacidosis at Initial Presentation of Type 1 Diabetes in a Prospective Cohort Study of Children. Diabetes Care 2014; 37:1554-62
21. 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 – a pilot study using two nation-wide population based quality registries. Pediatric Diabetes 2014; 15: 229-35
22. Duca LM, Wang B, Rewers M et al. Diabetic ketoacidosis at diagnosis of type 1 diabetes predicts poor long-term glycaemic control. Diabetes Care 2017; 40:1249-55