May 18, 2015 - This week's post is also available from the Cochrane Child Health blog.
I am sure you have heard. Type I diabetes is growing in both prevalence and incidence every year. This year alone, nearly 65,000 children and youth under the age of 15 will be diagnosed with type 1 diabetes worldwide . Next year, there will be a 3% increase in the incidence of diagnosis . Unfortunately, this trend is not expected to change in the near future.
Upon diagnosis, 10-70% of children will present with diabetic ketoacidosis (DKA) . Characterized by hyperglycemia, acidosis, and ketonuria, DKA is a very serious condition that carries substantial risk for life threatening complications, like cerebral edema. Moreover, in comparison to adults, children are at a high risk for severe complications. Because of this, DKA is the most common cause of diabetes related death in kids .
It remains unclear whether presenting in DKA at diagnosis is indicative of a more severe form of type 1 diabetes, or if it is linked to delayed diagnosis. However, we do know that children who present with DKA at diagnosis have a poorer long term prognosis, with diminished glycemic control, less residual β cell function for up to two years after diagnosis, and a decreased incidence of remission .
The mean duration between the onset of symptoms and development of DKA is 14 days, and over one third of children will have at least one medical consultation in this period prior to diagnosis . This represents an ideal time for identifying and triaging children at high risk for developing DKA. To do this, evidence-based risk factors for the development of DKA in children need to be identified.
Evidence-based factors associated with DKA at type 1 diabetes diagnosis
Usher-Smith et al. conducted a systematic review, including 46 studies with over 24,000 children and youth (ages 0-21 years) from 31 different countries, to determine factors associated with diabetic ketoacidosis at the diagnosis of type 1 diabetes in children and young adults. Together, 23 different factors were considered in this review. Here is the key evidence you need to know to identify a child at risk for presenting in DKA at type 1 diabetes diagnosis.
Age: Children less than 2 years old were three times more likely to present in DKA than children 2-5 years old.
Ethnicity: Because the populations included in the studies were too heterogeneous, the frequency of DKA could not be determined for specific ethnic groups. However, 5 studies compared differing pairs of ethnic groups, and consistently found the ethnic minority group experienced an increased risk of DKA.
Body mass index (BMI): Children with lower BMIs were at an increased risk for DKA.
Health insurance status: In the United States, children who had either no health insurance or Medicaid were three times more likely to present in DKA at diagnosis when compared to children with private health insurance.
Family income, parental employment, and social status: Children of low SES were at an increased risk for presenting in DKA.
Diagnostic error: Children who were not diagnosed with type 1 diabetes on their first medical consultation due to diagnostic error were three times more likely to present in DKA at diagnosis. Diagnostic error was significantly more likely in young children. The mean age of children presenting in DKA at diagnosis whose diagnosis was missed on the first medical consultation was 5.4 years, compared to mean age of 8.8 years in children whose diagnosis was not missed.
Delayed treatment and presence of structured diabetes team: One European multicenter study showed a greater than 24 hour delay between diagnosis and treatment led to a small increased risk of presenting in DKA at diagnosis. One Kuwaiti study showed that children diagnosed in hospitals without a structured diabetes team were more likely to present in DKA.
Preceding infection or febrile illness: Having a preceding infection or febrile illness increased the risk of presenting with DKA at diagnosis.
Family history of diabetes: Children who had a first-degree relative with type 1 diabetes were six times less likely to present in DKA on diagnosis.
Parental education: High parental education was protective against DKA, however, the definition of “high” education varied depending on the location of data collection in the included study.
Background incidence of type 1 diabetes: Children who lived in an area with a higher background incidence of type 1 diabetes were less likely to present in DKA.
Factors with no or an unclear effect on rate of presentation in DKA at diagnosis:
The following factors had no impact on the rates of presentation in DKA at diagnosis, or their impact could not be adequately assessed due to limitations of the data: sex, parental consanguinity (i.e., blood relation to a parent with type 1 diabetes), family structure, rural or urban residence, delayed diagnosis, and number of medical consultations before diagnosis.
Summarizing the evidence
The authors of the review concluded: “Younger age, diagnostic error, ethnic minority status, lack of health insurance in the US, lower body mass index, preceding infection, and delayed treatment were all associated with an increased risk of diabetic ketoacidosis, while having a first degree relative with type 1 diabetes at the time of diagnosis, higher parental education, and higher background incidence of type 1 diabetes appear to be protective.”
Implications for practicing clinicians
The authors of the review highlight: “As with other serious illnesses in children, differentiating the occasional child with a serious illness from the large number with minor undifferentiated illness is challenging. The relatively easy access to point of care tests for hyperglycemia, ketonemia, and glycosuria, however, means that diagnosis does not require access to specialist diagnostic services but, instead, a high index of suspicion. Our findings suggest that clinicians should be particularly alert for diabetic ketoacidosis in children under 5 years old, those from ethnic minority groups, and those from families with low education level or socioeconomic status.”
Translating Emergency Knowledge for Kids (TREKK):
1. Karvonen, M. (2006). Incidence and trends of childhood Type 1 diabetes worldwide 1990-1999. Diabetic Medicine, 23(8), 857-866. doi: 10.1111/j.1464-5491.2006.01925.x
2. Usher-Smith, J. A., Thompson, M. J., Sharp, S. J., & Walter, F. M. (2011). Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: A systematic review. BMJ, 343(7815). doi: 10.1136/bmj.d4092