Edited by Frank J. Snoek and T. Chas Skinner
Treatment Issues for Children Under 6 Years of Age
Once diagnosed, the basic goals of diabetes therapy for children under the age of 6 years are similar to those recommended to all children and adolescents and include the avoidance of high and low blood glucose levels and the maintenance of normal growth and development.
However, due to the continued development of the central nervous system, young children are particularly vulnerable to the debilitating consequences of recurrent hypoglycemia.
There is a growing body of evidence supporting the negative consequences, mild, cognitive deficits, resulting from overly aggressive attempts to normalize metabolism in young children. Ack et al.27 reported modest cognitive deficits in patients with a younger age of onset of type 1 diabetes. Others also reported brain damage as a result of severe hypoglycemia, particularly in young children.28,29 A series of studies by Ryan et al.,30–32 using a battery of neuro-behavioral tests, identified significant differences between youth with diabetes compared with control subjects on measures of verbal intelligence, visual-motor coordination, and critical flicker threshold. Additionally, children diagnosed with diabetes under 5 years of age manifested significant cognitive deficits when evaluated during the adolescent years, probably resulting from symptomatic or asymptomatic hypoglycemia occurring earlier in life before final maturation of the central nervous system. In another study by Rovet et al., 33 children diagnosed under 4 years of age scored lower than other children with diabetes diagnosed later in childhood and lower than non-diabetic sibling controls on tests of visual-spatial orientation but not on verbal ability. Hypoglycemic seizures were found to occur with greater frequency in the group of children diagnosed under 4 years of age compared with those diagnosed at older ages, suggesting that severe hypoglycemia may impair later cognitive functioning.33
Golden and colleagues34 collected longitudinal data on the frequency of hypoglycemia from the time of diagnosis in a sample of 23 children with diabetes onset prior to the age of 5 years. Correlating this data with subscale scores on the Stanford-Binet Intelligence Scale yielded no significant findings between frequency of severe hypoglycemia and any of the subscales. Importantly, it was the frequency of asymptomatic and mildly symptomatic hypoglycemia that was significantly correlated with lower scores on the abstract/visual reasoning scale, indicating that even mild or asymptomatic episodes of hypoglycemia can have a negative cumulative effect on cognitive functioning.
In the previously described studies, no measurements of neurocognitive functioning were made near the time of diagnosis to rule out the possibility that the metabolic decompensation of diabetes onset affected such functioning. Two studies have followed children with diabetes prospectively from diagnosis using neuropsychological assessments. The preliminary findings of Rovet and colleagues 35 indicated no evidence of neurocognitive impairment in these children at diagnosis or one year later, but the authors reported that they may not have followed subjects long enough to observe any impairment. Northam and colleagues36 compared the performance of children with type 1 diabetes on standardized measures of general intelligence, attention, speed of processing, memory, learning, and executive skills with the performance of control subjects. At 3 months post-diagnosis there were no differences between groups, but at 2 years post-diagnosis, children with diabetes demonstrated smaller gains, particularly in the areas of information processing speed, acquisition of new knowledge, and conceptual reasoning skills. The subset of the diabetes sample that performed the worst were those children with early onset of diabetes, which further suggests an early onset effect.36
In light of these findings, suggesting that even asymptomatic hypoglycemia in young children with developing nervous systems can be deleterious, prevention of severe and recurrent hypoglycemia is of paramount importance.27–40 In addition, infants and toddlers are unable to verbalize when they are suffering from hypoglycemia, which can lead to delayed treatment, unconsciousness, and/or seizures. A retrospective review of patients less than 9 years of age at Mayo clinic found that 45-55 per cent of children under 5 years of age had experienced severe hypoglycemic reactions compared with 13 per cent of children between 5 and 9 years of age.41 The current trend of intensive insulin therapy as advocated by the Diabetes Control and Complications Trial1,2 for persons over 13 years of age must be implemented very cautiously in these vulnerable young patients.14,37–41 Therefore, age-specific blood glucose target ranges with the provision for wide glycemic excursions should be the rule rather than the exception.
Achieving optimal glycemic control in this age range is further complicated by the finicky eating habits, erratic physical activity, and rapid growth of young children. Treatment goals must therefore be individualized to provide safe and effective medical treatment, yet also permit the young child to master the normal developmental tasks of childhood. For example, the toddler who is a picky, pokey eater may be best suited to rapid-acting insulin analogue injections after meals rather than prior to the meals in order to avoid frantic parents who are unable to ‘force’ their child to eat. Such insulin administration techniques may reduce the mealtime stresses experienced by many families of toddlers with diabetes.
In recent years, continuous subcutaneous insulin infusion therapy, or ‘pump’ therapy, has increasingly been used in young children. Several studies have shown that insulin pump therapy is a safe alternative to multiple daily insulin injections and may be associated with improved quality of life for families coping with diabetes..42–46 One of the most significant findings for parents of young children with diabetes is the reduced rates of severe hypoglycemic reactions associated with insulin pump therapy.44–48 In a randomized, controlled study of pump therapy in preschoolers by DiMeglio et al. did not find clinically significant differences in glycemic control in preschool patients on pump therapy versus intensive multiple daily injections or differential frequency of several hypoglycemias in patients. However 95 per cent of families randomized to pump therapy during the study continued such therapy after the study period.43 Pump therapy also allows greater convenience and lifestyle flexibility, such as meal timing, as parents can adjust the timing of insulin bolus delivery in the same manner as using rapid acting analogues. Interestingly, Litton et al. found that the frequency of parental contact with their health care providers decreased by 80 per cent after starting pump therapy, which they interpreted as a reflection of increased parental confidence with their diabetes management skills.44
Based on these studies, it appears that continuous subcutaneous insulin infusion therapy is an effective treatment alternative for young children. However, long-term outcome studies of children started on pump therapy as infants or toddlers are needed, especially in light of the finding of increased episodes of mild hypoglycemia by DiMeglio et al.43 As with all management issues, the decision to start pump therapy must be individualized to each family’s lifestyle and abilities. Pump therapy can be more expensive than injections and requires more training, which may preclude its use in some families.
If multiple daily injections are used, glargine, a recently introduced long-acting insulin analogue with no appreciable peak action, has been shown to significantly reduce hypoglycemia, especially nocturnal hypoglycemia, in children.49,50 By decreasing hypoglycemic events, which precipitate so much stress for families with a young child with diabetes, it is hoped that these new management tools can continue to improve the quality of life for these families.
Next Week: Diabetes in School-aged Children
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