Abstract
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Despite the obvious potential that real-time continuous glucose monitoring (CGM) would seem to offer, when the JDRF randomized clinical trial showed no benefit in decreasing HbA1c in subjects 15–24 years of age, questions remained about the utility of CGM in youth. 5 However, those using CGM >6 days per week had significant decrease in HbA1c levels (P<0.001) and greater satisfaction with CGM (P=0.001) than those with less frequent use. 6 In 146 children 4–10 years of age, the Diabetes Research in Children Network (DirecNet) Study Group similarly revealed no change in HbA1c levels and only 41% of children averaging >6 days/week of CGM use at 6 months despite high parental satisfaction. 7 Unlike in the JDRF group, however, the DirecNet patients had no association between change in HbA1c from baseline and the overall amount of CGM sensor wear. Despite high parental satisfaction with CGM in the DirecNet study, fear of hypoglycemia did not decrease, a fact that the investigators hypothesized may have led to parents not using CGM data to tighten blood sugar control. Therefore, it appears that some of the impediments to improving blood sugar control with CGM in children may vary by age of the child, with the younger ones less likely to receive more aggressive blood sugar management when using CGM and the older ones struggling more with the hassles of CGM use. Even among the highly motivated participants of these trials, a surprising deterioration of CGM use across the pediatric age range was common, and it will likely take a combination of improved comfort and accuracy, decreased sensor cost, and lower blood sugar targets for CGM to make a truly satisfactory impact in this population. As CGM devices evolve, continued studies in these age groups will be important.
Even without decreasing HbA1c levels, reducing the frequency and severity of hypoglycemia is an important goal. Using CGM in 176 patients with T1D >8 years of age, the JDRF Study Group demonstrated a median of 7.4% of nights with a hypoglycemic episode that lasted ≥2 h on 23% of those nights. 8 Randomization to CGM use for 6 months in 120 children and adults with well-controlled diabetes demonstrated a 50% decrease in the time spent in hypoglycemia, 9 although no published analysis specifically isolated the pediatric patients. Studies of adequate size have not yet been done to determine if CGM use decreases either the time spent in hypoglycemia or the number of moderate or severe hypoglycemic events in youth.
A group that could particularly benefit from CGM is preschool-age children. Repeated hypoglycemia in this population is quite undesirable because of known adverse effects. 10 In these patients, it is the parents who must make the decision to use CGM, in contrast to older children and adolescents, for whom the parent and the patient decide together. In 23 children <4 years of age, despite no change in HbA1c level, DirecNet showed high parental satisfaction with CGM and >40% of patients still using the device >6 days/week at 6 months, with 100% of parents responding that CGM helped them learn how to treat hypoglycemia better. 11 Therefore, although CGM use may not apply to all patients in this age group, it does have the potential to help some selected families by displaying glucose reading and trend graph slope when it is not always practical to use a glucometer. With the Food and Drug Administration's (FDA's) February 2014 approval of the Dexcom™ (San Diego, CA) G4 Platinum CGM device for patients as young as 2 years of age, this tool will be more widely available for pediatric diabetes. Because of the unique challenges to good glycemic control in the youngest patients with diabetes, studies of both hypo- and hyperglycemic outcomes with CGM use in this age group will be vital.
For those children using insulin pumps, automatic suspension of insulin delivery based on a low CGM reading (threshold suspend) may offer a significant advance. In a small cohort of 21 patients 1–18 years of age with a low glucose threshold set at 75 mg/dL (4.2 mmol/L), there were 0.89 automatic suspension events per day, with 24% of those events lasting the full 2 h. 12 This rate is similar to that seen in a retrospective analysis of 935 users of Medtronic's (Northridge, CA) Veo™ system, first available in 2009 in Europe. 13 In September 2013, the FDA finally approved Medtronic's MiniMed 530G with Enlite™, the first threshold suspend system available in the United States. Many parents of pediatric patients with T1D express fear of nocturnal hypoglycemia, 14 and despite being off-label for those under 16 years of age, threshold suspend, even independent of improvements in HbA1c and hypoglycemia, may improve quality of life for parents who currently sleep restlessly and awaken frequently to check blood sugar levels during the night. Unfortunately, data on the safety and efficacy of threshold suspend in pediatric patients are limited, and no reports focus on the very young.
In summary, CGM has been shown to benefit some pediatric patients with T1D. As new devices and applications become available, they will be widely used in children and adolescents despite evidence being less complete than in adults. If we are to optimize diabetes management across these age groups, it will only be possible with access to CGM technologies and a clear understanding of how best to use them.