CSII represents an attractive treatment option for children and adolescents with type 1 diabetes because it offers the potential for achieving all current treatment goals for these patients: near-normal glycaemic control, a low incidence of hypoglycaemia and improvement in quality of life . Nevertheless, CSII remains largely underused: for example, recent data indicate that only 10–14% of paediatric diabetic patients in Germany are receiving CSII [19, 20]. The key barrier to CSII therapy is economic, as there is no consistency regarding reimbursement from Health Authorities across Europe. In countries where funding is not readily available, access depends primarily upon the determination of the physician.
The results of this study support and extend those of the previous PPSG survey , and show that effective glycaemic control, with a low risk of hypoglycaemia, can be achieved with CSII therapy in many children and adolescents with type 1 diabetes. Although this survey is limited to some extent by its cross-sectional nature and a lack of a standardised approach to pump therapy in children, it nevertheless gives some insights into successful paediatric pump therapy regimens in a large patient population from 17 countries.
This study has highlighted the marked variations in patterns of pump use between centres, for example in terms of the number of daily boluses and the proportion of the daily dose given in pump form. This is consistent with the finding in the Hvidore Study that the HbA1c concentrations achieved with intensive therapy varied markedly between centres . It is important to remember that CSII and multiple daily injections are both viable strategies in children and adolescents, and that the final choice of treatment for an individual patient will require a dialogue between the patient, their parents or guardians, and the physician. Currently, strategies for tailoring CSII regimens to the needs of the individual patient tend to be empirically based, rather than evidence based . Aspects that require particular attention in children and adolescents include patterns of basal and prandial insulin requirements and the selection of catheters and needles .
An important finding was that the use of frequent daily boluses and a lower proportion of basal insulin achieved significantly better glycaemic control than the use of fewer boluses and a higher proportion of basal insulin. This is consistent with the findings of a previous study with CSII, which showed a significant correlation between missed mealtime boluses and elevated HbA1c . Indeed, in the present study the use of more than seven boluses per day was the strongest single predictor of an HbA1c level <7.5%; similar findings have been reported by Burdick et al. . The ability to deliver multiple daily doses represents an important potential advantage of CSII over multiple daily injections. This is particularly true when short-acting insulin analogues are used to achieve prandial control as was the case in 99% of the patients in the present survey. A recent editorial  has emphasised that basal and overnight glucose levels are the major determinants of HbA1c levels in patients with poor glucose control, and hence such analogues produce the greatest benefit when glucose is well controlled; indeed, these analogues produce the greatest reductions in HbA1c concentrations in patients receiving CSII therapy. It should be noted, however, that because of the lack of electronic data regarding blood glucose measurements or meals in this study it remains to be determined whether multiple boluses are predominantly associated with meals or correction for blood glucose values.
An apparently paradoxical finding of this study was that the use of CSII for >1.5 years was associated with a higher HbA1c level. This probably reflects an age-related effect; as would be expected, the duration of use tended to increase with age and hence the longest durations were seen in the adolescent group, who also had the highest HbA1c levels. Several studies have shown that HbA1c levels in adolescents are typically >8%, and that reduction is often difficult to achieve in this group [5, 24]. Indeed there was a negative association between age and number of boluses, and it is likely that missed mealtime boluses in the adolescent age group contributed to this . In this age group, it could be beneficial to support CSII with a higher basal dose to compensate for missed boluses or additional food intake. This remains an area for further investigation. In a recent matched-pairs comparison of CSII with multiple daily injections the best long-term results were seen in the youngest age group . These findings would be consistent with the finding in the present study that HbA1c was significantly higher in patients in whom high HbA1c was the indication for CSII therapy than in those with other indications. The finding that HbA1c concentrations were greater in adolescents than in younger age groups could reflect greater parental supervision of treatment in young children, as reported in other studies .
The finding that a longer duration of CSII use was associated with higher HbA1c is at variance with a previous meta-analysis , which found that patients who received pump therapy for at least 1 year showed significant improvements in glycated haemoglobin, whereas no significant improvement was seen in patients treated for <1 year. Nevertheless the finding that many patients included in the previous survey increased their number of boluses between the previous survey and the present study indicates that constant re-education and motivation can achieve better long-term glycaemic control with CSII. Thus, the message of our findings may be that it is important to download the electronic pump memory, and to convince the patients to take at least the minimum number of doses.
In view of the finding in this study that HbA1c concentrations were higher in adolescents than in younger children, it seems paradoxical that there was no association between the risk of high HbA1c and age. In contrast, in the Hvidore study, HbA1c increased by a mean of 0.046% (p < 0.0001) with each year of age . It is possible that in the present study any effect of age was masked by the influence of treatment duration.
The low incidence of severe hypoglycaemia in this study compares favourably with that in the Hvidore Study, in which the overall incidence of severe hypoglycaemia was 22 events per 100 patient-years and the incidence increased to almost 60 events per 100 patient-years in preschool children . A previous study, involving 95 children and adolescents who were followed for a median of 28 months after starting CSII therapy, reported incidences of 7.9 events per 100 patient-years for severe hypoglycaemia and 0.7 events per 100 patient-years for DKA . The even higher rate of DKA in the present study may be a reason for concern as errors in pump use could have been a potential cause. However, the significantly higher HbA1c in the DKA group, and the lack of an association with age or CSII duration, make it likely that similar risk factors for DKA apply with CSII as with injection therapy .
As noted above, a possible limitation of this study is the open and uncontrolled design. However, the study was designed to investigate the efficacy and safety of CSII therapy in a large patient population under ‘real-life’ conditions. Such studies can provide important insights into the benefits and risks of a treatment in routine clinical practice, in contrast to the controlled conditions that prevail in clinical trials . The ability to download data recorded in real time under everyday conditions in a large group of children from many different countries and cultures should provide important insights into the optimal use of CSII therapy, which arguably might not be apparent in randomised controlled trials. These insights should facilitate the identification of patients who would derive most benefit from CSII therapy. A particular strength of this study was the centralised measurement of HbA1c, which eliminated the possibility of inter-centre variability in HbA1c measurements, thus facilitating analysis of factors affecting glycaemic control during CSII.
In conclusion, this study has shown that CSII provides convenient and flexible insulin delivery during routine treatment in many children and adolescents with type 1 diabetes. It has also highlighted the importance of frequent daily boluses and <50% basal insulin for good glycaemic control, which is relevant to both CSII and multiple dose insulin therapy. A follow-up longitudinal study will investigate the long-term outcome in these patients.