This study represents the first of its kind investigating prospective memory and glycemic control in children with type 1 diabetes mellitus. While as a whole this was a largely negative study, the association between glycemic control and the PROMS 20 minute EBT warrants further exploration. Deficits in EBT could help explain why children, even those with a long standing history of T1DM, have difficulty remembering to check BG and take insulin at meal times, as these events require event-based prospective memory. It is not clear why the only significant correlation between HbA1C and PROMS was the 20 minute EBT and not the shorter EBT. Multiple inputs at the outset of the PROMS and the length of time from request to cue for the task may have contributed to tendency to forget the task. However, this might best mimic expectations outside of the laboratory setting and could impact upon daily diabetic care. Positron emission tomography scans have demonstrated that EBT and TBT activate different areas of the rostral prefrontal cortex  and at least one study has shown that deficits in EBT and TBT are not always congruent .
Our study also found a modest correlation between HbA1C and parental concerns about the children’s working memory and metacognition as assessed by the BRIEF. This finding is consistent with that reported by McNally et. al who concluded that higher levels of executive functioning (i.e. lower reports of parental concern on the BRIEF) was associated with increased treatment adherence which predicted improved HbA1C levels .
Most studies involving pediatric T1DM and cognition concluded severely low BG increases the risk of learning difficulties and need for special education ; decreased spatial ability and slower motor speeds ; impairments in memory, learning, and executive functioning ; weaker visual and verbal delayed recall [7, 26]; poorer verbal short term memory ; inferior analytic skills ; and problems with attention . Two studies argue that severe hypoglycemia has no impact on cognition [28, 29]. Another concluded that subtle hypoglycemia actually led to an increase in test scores in academic achievement, memory, verbal comprehension and general cognition . Although not one of our primary aims, our study only found a significant correlation between increased hypoglycemic events and increased episodes of diabetic ketoacidosis (r= 0.45, p<0.001). While the relationship between increased episodes of hypoglycemia and lower full-scale IQs trended towards significance (r= −0.185, p= 0.076), more frequent episodes of severe low BG did not impact performance on the PROMS or academic achievement.
Hyperglycemia, gender, and SES have also been investigated as causal factors of cognitive dysfunction in pediatric T1DM. Conflicting results about the effect of acute hyperglycemia have been published. One study concluded that acute hyperglycemia, defined as >360 mg/dL, had no effect on cognitive functioning . A later study demonstrated that when BG was acutely raised between 360–540 mg/dL in 12 children with T1DM, 8 of the children had a decrease in their performance IQ . Receptive language scores among thirty-six preschoolers with a mean BG of 174mg/dL were found to be inversely correlated with higher blood glucoses; ambient blood glucose did not correlate with other measures of cognitive or motor testing . In the current study, no correlations were seen between ambient BG and PROMS scores, performance on digit span testing, or full scale IQ. Studies testing prospective memory under both euglycemic and hyperglycemic conditions in the same child need to be conducted before conclusions regarding the effect of elevated BG on this component of memory can be made. Several studies have found that boys with T1DM have a higher incidence of learning problems compared to girls with T1DM [33–36]. Our data did not support these findings as gender did not impact prospective memory or cognitive test scores nor did parents of sons report more concerns on the BRIEF. Although lower SES has also been implicated as an additional risk factor for cognitive incongruities  this was not found amongst our children.
There are several limitations of this study. While the prospective memory screen used in our study was specifically developed with a pediatric population in mind and has face validity, it is not a standard tool used in psychometric evaluation. However, no other “gold standard” exists. One could argue the shorter tasks measured working memory and not prospective memory, thereby limiting our findings.
The demographic characteristics of our participants were not representative of a broader T1DM population. Our final study population consisted primarily of academically high-achieving children from well-educated, middle to upper class families. As prospective memory is an integral component of daily functioning and success, this self-selected group likely has higher prospective memory skills compared to a more general population of families with children with T1DM. Second, the majority of the participants used intensive insulin regimens and maintained desirable HbA1Cs. It is possible that the prescribing physicians unknowingly assessed aspects of prospective memory skills of these children and their parents and deemed them capable of remembering to carry out the tasks needed for success with an intensive insulin regimen. Third, patients with lower HbA1C, and arguably better prospective memory, may have been more willing to volunteer for the study. Patients with poor glycemic control often failed to come to appointments, theoretically due to deficits in prospective memory, and thus had fewer opportunities to be asked to participate. Generally these patients and their families are seen as “unmotivated” to care for T1DM by health care providers; this lack of motivation may actually represent poor prospective memory skills which make diabetic care that much more challenging for these families.
Mean HbA1C of the 20 consented children who ultimately did not participate in the study despite reminder phone calls and opportunities to reschedule was 9% compared to 7.9% of those who completed the study. As the reminder phone calls were directed to the parents, one must question the adults’ prospective memory and its role in the children’s glycemic control. Future examination of this relationship is warranted, particularly in younger patients in whom adults generally assume responsibility for providing the child’s diabetic care.
The lack of significant relationships between frequency of hypoglycemia and prospective memory, academic achievement, and full-scale IQ may not be generalizable to a more diverse sample of children with higher rates of hypoglycemia. Only 20% of the families reported one or more episode of severe hypoglycemia. The accuracy of this occurrence rate is limited by parental recall and individual interpretation of severe hypoglycemia. The lack of association between lower SES and cognitive functioning may also be due to the homogeneity of our sample, with virtually all of the families earning well above our national poverty threshold.