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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Increasing antidiabetic drugs use in youths has been reported in the USA, however there is a lack of epidemiological evidence in the UK.
• There is an increase in the prevalence of both type 1 and 2 diabetes, but precise estimates are difficult to obtain and as such are uninformative for future health services planning.
• The prevalence of children receiving insulin and oral antidiabetic drugs has increased twofold and eightfold, respectively, between 1998 and 2005.
• The data reflect the prevalence of both type 1 and type 2 diabetes rapidly increase in recent years.
• The prevalence of antidiabetic drug use increases with increasing age, especially among those aged 12–18 years.
• Consideration needs to be given to the funding and design of future services for children and particularly adolescents with diabetes to take account of these epidemiological findings.
AIMS Despite evidence of an increase in the incidence of both type 1 and type 2 diabetes in youths, there are few data on the prevalence of either type in children and adolescents. The aim of this study was to investigate the prevalence of childhood diabetes over an 8-year period in the UK.
METHODS This was a retrospective cohort study that covered 8 years (January 1998 to December 2005) of UK IMS Disease Analyzer (IMS DA) data. The cohort comprised all children and adolescents aged 0–18 years who received at least one antidiabetic drug prescription during the study period. The prevalence of antidiabetic drug prescribing was used as a proxy for diabetes itself.
RESULTS Data were available on 505 754 children aged 0–18 years and a total of 37 225 antidiabetic prescriptions were issued. Insulin use increased significantly from 1.08 per 1000 children [95% confidence interval (CI) 0.96, 1.20] in 1998 to 1.98 (95% CI 1.80, 2.10) in 2005 (P < 0.001), more markedly in those aged 12 and 18 years. The use of oral antidiabetic drugs for diabetes treatment rose significantly from 0.006 per 1000 children in 1998 (95% CI 0.0043, 0.017) to 0.05 (95% CI 0.025, 0.080) (P < 0.001) in 2005.
CONCLUSIONS This study indicates a significant increase in prevalence on both type 1 and type 2 diabetes treatment in children and adolescents in the UK. Thus, this supporting evidence from other sources that the prevalence of childhood diabetes is rising rapidly. Further epidemiological studies are required to investigate the aetiology and risk factors.
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Diabetes is one of the most common chronic conditions of childhood and there has been a marked increase in incidence of both type 1 and type 2 diabetes in children and adolescents over the past 20 years [1–3]. In the USA, more than 13 000 children are diagnosed with type 1 diabetes each year . The incidence of type 1 diabetes in the USA is about seven per 100 000 per year in children aged ≤4 years, 15 per 100 000 per year in children aged 5–9 years, and about 22 per 100 000 per year in those aged 10–14 years . In 2007, the incidence rate of both type 1 and type 2 diabetes was 24.3 per 100 000 person-years in young people aged <20 years in the USA . Approximately 75% of all newly diagnosed cases of type 1 diabetes occur in individuals younger than 18 years old. In the UK, it was reported that the incidence of type 1 diabetes in children aged ≤14 years ranged from 15 to 26 per 100 000 per year during the 1990s, with an estimated annual increase in incidence of 4% per year. Also, the UK is one of the countries with the highest incidence rate of type 1 diabetes in children, ranking fifth out of 57 countries . Previous studies have estimated the incidence of diabetes in young people using diabetes registries to monitor new cases. There is sufficient evidence to demonstrate that the incidence of children with diabetes is rising [1–3, 8].
However, studies investigating the prevalence of diabetes in children and adolescents are lacking. This information is particularly important from a health policy point of view as it will enable the monitoring of disease burden, which is directly related to the planning of healthcare resources. In 2005, the US National Institute of Health estimated that the prevalence of diabetes in people aged ≤ 20 years was 0.22%; however, the authors suggested that nationally representative data that would be needed to monitor diabetes trends by type are not available to date . As a result, a 5-year project was set up and the findings will be reported in the near future. In the UK, it was estimated that 20 000 children and adolescents have diabetes . However, similar to the USA, national representative data for diabetes trends are lacking.
The prescribing of insulin is an excellent proxy for estimating the prevalence of type 1 diabetes in the UK as it is mainly prescribed for type 1 diabetes and is not normal practice to manage type 2 diabetes in children with insulin. Previous studies have applied this approach to estimate the prevalence of diabetes in the USA and Scandinavia [10–13]. The treatment of type 2 diabetes is more complex. For example, metformin is also being used for the treatment of polycystic ovarian syndrome (PCOS), obesity and for impaired glucose tolerance. In addition, type 2 diabetes may persist unrecognized in obese adolescents or be managed by diet alone. Therefore, the approach of using oral antidiabetic drugs as a means to estimate the prevalence of type 2 diabetes needs to be cautious. In the UK, children and adolescents with diabetes are almost entirely managed in hospital, whereas the prescribing of insulin and oral antidiabetic drugs is mostly undertaken in general practice. Therefore, the national general practice databases are appropriate to investigate the prevalence of childhood diabetes by using antidiabetic drug prescribing as a proxy for diabetes itself.
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The IMS DA study population included 505 754 children and adolescents aged between 0 and 18 years during the study period (Table 1). Among these, 37 225 antidiabetic prescriptions were issued to 1098 study subjects. Insulin accounted for the majority of antidiabetic prescriptions (98.1%) (Table 2). The age-specific prevalence of all antidiabetic drugs (including insulin) between 1998 and 2005 is shown in Figure 1. There was a linear increase in prevalence with increasing age from 0.06 per 1000 children at the age of 1 year to 3.07 per 1000 at 18 years.
Table 2. Number of antidiabetic prescriptions in children and adolescents aged 0–18, stratified by ATC (Anatomical Therapeutic Chemical) classification
|ATC codes||Drug name||No. of prescriptions||%|
|A10C1||Human insulin analogue fast acting||8 920||24.4|
|A10C2||Human insulin analogue intermediate acting||4 281||11.7|
|A10C3||Human insulin analogue intermediate + fast acting||20 127||55.1|
|A10C4||Human insulin analogue intermediate + long acting||319||0.87|
|A10C5||Human insulin analogue long acting||2 735||7.5|
|A10C9||Other human insulin||1||0.003|
|Total|| ||36 512||100|
|Oral antidiabetic drugs|
|A10B1||Sulphonylureas|| || |
|A10B2||Biguanides|| || |
|A10B4||Glitazones|| || |
|A10B9||Other oral antidiabetics|| || |
Figure 2 shows the prevalence of insulin and oral antidiabetic drug use during the period covered. Insulin use rose significantly from 1.08 per 1000 children (95% CI 0.96, 1.20) in 1998 to 1.98 per 1000 (95% CI 1.80, 2.10) in 2005 (P < 0.001). Similarly, the use of oral antidiabetic drugs significantly increased during the study period from 0.02 per 1000 children (95% CI 0.006, 0.04) to 0.16 per 1000 (95% CI 0.11, 0.21) (P < 0.001). Figure 3 shows the age-specific prevalence of insulin use. The use of insulin was significantly increased at age 6–18 years. Among the group of oral antidiabetic drugs a total number of 713 prescriptions were issued to 128 children during the study period. Metformin (n= 613 prescriptions, 86%) was the most commonly prescribed oral antidiabetic drug (Table 1). Of 103 children who received metformin, 23 (22.3%) were recorded as being prescribed this drug for the treatment of PCOS. The prevalence of oral antidiabetic drugs used solely for the treatment of diabetes increased significantly from 0.006 per 1000 children in 1998 (95% CI 0.0043, 0.017) to 0.05 per 1000 children in 2005 (95% CI 0.025, 0.080) (P < 0.001). Only 26 patients from the study cohort received both insulin and oral antidiabetic drugs; therefore the increase in insulin is unlikely to be caused by the increase in type 2 diabetes.
As insulin accounted for the majority of antidiabetic prescriptions, we validated its prevalence using the GPRD, where a total of 3466 subjects aged 0–18 years received insulin between 1998 and 2005. The data also show a steady increase amongst subjects aged 6–11 and 12–18 years, with a significant rise from 1.26 per 1000 children (95% CI 1.16, 1.50) to 1.83 per 1000 children (95% CI 1.75, 2.11) in the 6–11-year-old group and 2.52 per 1000 (95% CI 2.40, 2.88) to 3.43 per 1000 children (95% CI 3.39, 3.83) in the 12–18-year-old group (P < 0.001) (Figure 4).
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The main finding of this study is that the use of insulin and oral antidiabetic drugs in children and adolescents has steadily increased in the UK. The overall prevalence of insulin use has almost doubled in children and adolescents, rising from 1.08 to 1.98 per 1000 children between 1998 and 2005. The prevalence of oral antidiabetic drug prescribing shows almost an eightfold increase. This suggests that the prevalence of both type 1 and type 2 diabetes is increasing rapidly, particularly among adolescents.
To our knowledge, this is the first large paediatric study in the UK. The strengths of this study are that, first, insulin prescribing is an excellent proxy to estimate the prevalence of type 1 diabetes, as diagnosed patients are rarely left untreated. Second, compared with questionnaire studies, the study is population based and does not rely on responses from clinicians and, as such, is less prone to under-reporting. Third, the study consists of a cohort of over half a million children, allowing us to provide a good estimate of the prevalence of treated type 1 and type 2 diabetes. Fourth, vigorous steps have been taken to conduct external validation of IMS DA data using the GPRD. These two databases cover approximately 8% of the UK population. The analyses from both databases demonstrated similar results that support the veracity of the findings. Therefore, these findings can be generalized to UK practice.
The major limitation of the study is that we were unable to identify patients with type 2 diabetes treated with lifestyle modifications such as diet alone , and asymptomatic undiagnosed type 2 diabetes patients. As a result, our study is likely to have underestimated the prevalence of type 2 diabetes. In addition, neither database contains ethnicity information, so it is not possible to investigate whether the increase in diabetes treatment is associated with changes in UK demographic structure, such as the increase in the young non-White population, which is more predisposed to diabetes [28–30].
This study has demonstrated a steady increase in the prescribing of antidiabetic drugs in children and adolescents. This is in line with a study using prescription claims data in the USA, which has shown an increase in the prevalence of antidiabetic drug prescribing from 1.85 per 1000 children (aged 5–19 years) to 2.66 per 1000 between 2002 and 2005 . Their study also revealed that the prevalence of antidiabetic drug prescribing among those aged 15–19 years was three times the rate seen in children aged 5–9 years, and 1.5 times that of children aged 10–14 years, which is the same trend as seen in our study.
In 1997, the American Diabetes Association (ADA) revised the diabetes diagnostic criteria . This could have affected the antidiabetic drug prescribing. However the evidence suggested the revised ADA diagnostic criteria caused an underestimate in adult studies [32–33]. Thus, it is unlikely that the increase of antidiabetic drug prescribing was due to the revision of diagnostic criteria. In April 2004, the National Quality and Outcome Framework (QOF) was introduced as part of the new General Medical Service to improve quality of services to patients through GPs. However, the increased antidiabetic drug prescribing was observed before 2004. Thus, this cannot be the cause of the increased prescribing .
Recently, attention and debate has focused on the rise in type 2 diabetes in children due to obesity; therefore, it is not surprising that we have identified an increasing prevalence of children receiving oral antidiabetic drugs for diabetes treatment. However, the magnitude of increase was unexpected. Metformin was the most commonly prescribed oral antidiabetic drug in our study cohort (86%). After scrutinizing the medical records of those subjects who received metformin, it became apparent that 22.3% had the drug prescribed for PCOS. Although the absolute number and prevalence of patients in our study cohort treated with oral antidiabetic drugs for type 2 diabetes was low, it still indicates that there has been a significant increase over the past 8 years.
A recent paper published by the British Paediatric Surveillance Unit has shown that the incidence of non-type 1 diabetes was 1.3 per 100 000 per year (children aged <17 years) in 2004–2005. However, there were no previous incidence data to demonstrate the magnitude of increase. This study, which is probably the first of its kind in the UK, systematically demonstrates the extent of the increase in the prevalence in recent years from 0.006 per 1000 children in 1998 (95% CI 0.0043, 0.017) to 0.05 per 1000 children in 2005 (95% CI 0.025, 0.080) .
We acknowledge that the actual prevalence of type 2 diabetes will be underestimated because of the undiagnosed asymptomatic cases and those controlled with diet alone. When comparing the prevalence of treated type 2 diabetes in our study with the only previous prevalence study of childhood type 2 diabetes in the UK , our prevalence (1.9 per 100 000 children in 2000) is almost 10 times higher than the previously reported prevalence of 0.21 per 100 000 children (<16 years) in 2000. The reason for this difference may be because approximately 25% of paediatricians in the previous study did not respond to the questionnaire, leading to underestimation of the prevalence. Furthermore, our study covers children and adolescents up to 18 years of age, and adolescents aged between 16 and 18 years are more likely to develop type 2 diabetes.
The most unexpected finding was the steady increase in the prevalence of insulin use, especially in adolescents. One possible explanation is that type 2 diabetes patients received combination treatment, i.e. insulin and oral antidiabetic drugs. However, in our study there were only 26 patients receiving both insulin and oral antidiabetics. Due to this small number, it is very unlikely that the increase in insulin use is due to an increase in type 2 diabetes. This also demonstrates that few patients received combined treatment (insulin and oral antidiabetic drugs). This is in line with the UK National Institute for Clinical Excellence guideline, which suggests that children and young people with type 1 diabetes should not receive acarbose or sulphonylureas (e.g. glibenclamide, gliclazide, glipizide, tolazamide or glyburide) combined with insulin, as these drugs may increase the risk of hypoglycaemia .
A systematic review of type 1 diabetes incidence trends during the period 1960–1996 has shown a significant rise in incidence of childhood type 1 diabetes. The average annual increase was 3.0% (95% CI 2.60, 3.30) . Similarly, a large European survey between 1989 and 1998 showed an annual increase of 3.2% (95% CI 2.70, 3.70) . A US study demonstrated that the incidence of type 1 diabetes in children <18 years old in Colorado was 14.8 per 100 000 person-years in 1978–1988 and 23.9 in 2002–2004 . A study from Australia has reported similar findings . Taking all the above information into consideration, the incidence of type 1 diabetes has continuously risen up to the present time. Hence, there is compelling evidence that the increased insulin prescribing in our study reflects an increase in the incidence and prevalence of type 1 diabetes in children and adolescents. In addition, the study shows a steady increase in the prevalence of type 1 diabetes particularly amongst patients aged 12–18 years. This is in line with a US study in which the prevalence of diabetes was estimated on the basis of prescription claim data. Their results showed that the prevalence of diabetes in adolescents aged 15–19 years was three times higher than the rate amongst children aged 5–9 years . In 2007, a study presented at the Diabetes UK conference showed that the incidence of type 1 diabetes in children aged <15 years almost doubled between 1985 and 2004 in the Oxfordshire region and that the largest rise was amongst children <5 years old . The authors suggested that this might be because the peak age of diabetes diagnosis is becoming younger in the UK. It should be noted that this study did not investigate children aged <15 years, which may explain why a steep rise in adolescents was not identified as shown in our study.