Pediatric Type 1 Diabetes and Neurocognitive Complications Cohort Study

Identifying Modifiable Risk and Protective Factors for Neurocognitive Complications of Pediatric Type 1 Diabetes

The proposed project will assess hypothesized risk factors (age of onset, Diabetic ketoacidosis (DKA) at presentation and glycemic control), as well as potentially modifiable protective factors (child sleep quality, caregiver distress, and use of diabetes devices). In addition, the study will optimize imaging protocols and processing tools to allow for harmonization of neuroimaging data across sites and scanners for the most robust analysis.

The onset of type 1 diabetes (T1D) in childhood results in clinically significant deficits in neurocognitive functioning that manifest in adulthood. These deficits have implications for adaptive functioning and diabetes management. Studies of neurocognitive function and brain development in T1D suggest that factors such as age of onset, diabetic ketoacidosis (DKA) at time of onset, and exposure to chronic hyperglycemia or severe hypoglycemia may increase risk or severity of these deficits, but findings are mixed. The majority of previous studies were limited by the use of adult or older adolescent samples, cross-sectional designs or short duration of follow-up, lack of racial and ethnic diversity, and small sample sizes. Age-related changes in neurocognitive function and vascular complications associated with T1D in adults make isolating mechanisms more complex. The knowledge gaps are critical because individuals with T1D may live for decades with reduced neurocognitive function. Building on previous work, it is hypothesized that several risk and protective factors for neurocognitive deficits will be evident in youth with T1D. First, sleep is a critical and potentially modifiable risk or protective factor for youth. Prior work has shown that the majority of school-age children do not obtain sufficient sleep (67%), and that sleep disturbances are related to poor glycemic control and risk for DKA, both of which have been posited to increase risk for neurocognitive deficits. Second, caregiver distress (i.e., symptoms of anxiety and depression) is a significant risk factor for child wellbeing, as exposure to maternal depressive symptoms increases children's risk for cognitive deficits and abnormal white matter diffusivity. Third, improved glycemic control via use of continuous glucose monitors and hybrid closed-loop insulin delivery systems, are potential protective factors for youth with T1D, as these devices decrease glycemic variability and limit time spent in hypoglycemia and hyperglycemia. Thus, a prospective longitudinal cohort study of young children with T1D is needed to identify modifiable risk and protective factors for neurocognitive complications. If specific risk or protective factors for adverse or optimal neurocognitive outcomes are defined, treatment protocols could be developed to limit neurocognitive complications associated with T1D.

Inclusion Criteria:

• Pediatric T1D sample: Children will be eligible if they meet the following inclusion/exclusion criteria:

  1. are between 6 -11 years of age
  2. have no history of afebrile seizure (not related to hypoglycemia) or sleep disorders other than insufficient sleep or insomnia
  3. no contraindications to high quality MRI of the brain (no metal implants or braces)
  4. no premature birth (<34 weeks) or low birth weight (<2,000g).

Comparison sample: Children will be eligible if they meet the following inclusion/exclusion criteria:

1. no known chronic medical conditions or intellectual disability
2. no known history of concussion or traumatic brain injury
3. no history of afebrile seizure; (4) no braces or metal implants

(5) no premature birth (<34 weeks) or low birth weight (<2,000g).

Parents or primary caregivers of all children will be eligible if they:

1. live with the child
2. read/speak English to allow use of validated parental questionnaires. The parent who is the primary caregiver of the child will be invited to participate.

Exclusion Criteria:

• N/A