Diabetes technology and treatments in the paediatric age group

Type 1 diabetes (T1D) is one of the most common chronic childhood diseases and its incidence has doubled during the last decade. The goals of intensive management of diabetes were established in 1993 by the Diabetes Control and Complications Trial (DCCT) (1). Children with T1D and their caregivers continue to face the challenge to maintain blood glucose levels in the near-normal range. It is important to prevent sustained hyperglycaemia which is associated with long-term microvascular and macrovascular complications and to avoid recurrent episodes of hypoglycaemia or hyperglycaemia, especially in young children, which may have adverse effects on cognitive function and impede efforts to achieve the recommended glycaemic targets. Advances in the use of technology that may help maintain the metabolic control goals for young people with T1D were centred on continuous subcutaneous insulin infusion (CSII) (2-4), continuous glucose monitoring (CGM) (5-7), and combining both technologies into a closed-loop system (8-10). The dilemma in paediatrics of patient selection for insulin pump therapy was found to be most successful in those with more frequent self-monitoring of blood glucose (SMBG) and younger age prior to pump initiation (2). Similarly, those who used a dual-wave bolus probably paid closer attention to their management and had lower HbA1c levels (3). The advantage of using a pre-meal bolus to improve postprandial glucose levels was shown to offer another potential method to improve glycaemic control (4). SMBG is an important component of therapy in patients with diabetes, especially in the paediatric age group. Standard use of glucose meters for SMBG provides only intermittent single blood glucose levels, without giving the 'whole picture' of glucose variability during the 24 h, and especially during the night, when blood glucose levels are seldom measured. Therefore, the use of a device such as real-time continuous glucose monitoring (RT-CGM) that provides continuous glucose measurements can help patients optimise glycaemic control. These devices may have the potential to increase the proportion of patients who are able to maintain target HbA1c values, to decrease glucose excursions and to decrease the risk of severe hypoglycaemia. Previous studies in paediatric T1D patients (11,12) have demonstrated that the frequency of CGM use was significantly associated with the effect of lowering HbA1c levels. The important STAR 3 study of 485 patients (156 children) with T1D showed the benefit of sensor-augmented pump therapy over remaining on multiple daily injections (MDI) (10). The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring (JDRF-CGM) studies were initially described in the 2009 Yearbook (13). Further reports of youths and adults in this study found that those with initial low HbA1c levels (< 7%) show a significant benefit from the use of CGM (5). Prolonged nocturnal hypoglycaemia was shown to continue to be a common occurrence in the entire cohort using CGM (7). Thus, there is an obvious need for closing the loop. Many patients with diabetes and especially parents of diabetic children dream about the invention of an 'artificial pancreas'. CSII and RT-CGM can be combined to form closed-loop systems. Insulin is then delivered according to RT-CGM data, as directed by a control algorithm, rather than at pre-programmed rates. Few closed-loop prototypes have been developed with advanced control algorithms, such as those that are based on model predictive control (14). The group at Cambridge studied 19 young people in closed-loop systems and was able to demonstrate that exercise and diet variations could be aptly managed (9). It is expected that closed-loop studies in young people will continue to multiply in future years. T1D is characterised by immune-mediated pancreatic β-cell destruction. Thus, a major goal in the treatment of T1D in youth will be in the area of prevention. The identification of increased levels of inflammatory markers in the SEARCH study of young people with T1D may provide an important clue (15). Most of the studies countered the diabetes process by immunomodulation and/or enhancement of β-cell proliferation and regeneration (16). An initial pilot trial of a tumour necrosis factor α (TNF-α) binding agent, Entanercept, showed benefit in preserving C-peptide production in 18 young people with newly diagnosed T1D. HbA1c levels were also lower in the treatment group (5.9% ± 0.5% vs. 6.98% ± 1.2%; p < 0.05) (17). Similarly, β-cell function was shown to be preserved in children receiving the lower of two doses of ingested human recombinant interferon-α (hrINF-α) in comparison with subjects who received placebo (18). A future larger trial of both of these agents will be of interest. In this review of the literature we have tried to select recent publications that offer some insight into these issues in paediatric patients with T1D.