Type 1 Diabetes and the Brain in Children

Study Overview
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Brief Summary
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The investigators have previously studied a group of young children with T1D using brain MRI, age-appropriate neurocognitive testing and continuous glucose monitoring, followed for 18 months. The investigators observed significant differences in gray matter volumes and white matter microstructure in the children with diabetes as compared to controls. These differences appeared to increase over time, with slower rates of brain growth in the T1D group (Mazelli, et al, Diabetes 2014; Barnea-Goraly, et al, Diabetes Care 2014; Mauras, et al, Diabetes 2015). In this new protocol the investigators will include the same children with T1D and healthy controls previously studied and recruit new similar subjects to replace those lost by attrition. The investigators will be using structural and functional brain MRI, neurocognitive testing and measures of glycemic control, to determine if changes in the brain persist or worsen over longitudinal follow up, and whether these changes are associated with measures of glycemic control and neurocognitive metrics as these children grow and progress through puberty.

Detailed Description
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Study participation will last about 2 to 2 1/12 years and will include a brain MRI without sedation, as well as a functional MRI and neurocognitive testing. The children with T1D will wear a continuous glucose monitor (CGM), will follow up every 3 months and will be asked to wear the CGM each time. The structural and functional MRI and neurocognitive testing will be repeated 2 yrs from baseline. The healthy controls will also undergo MRI and cognitive testing as well as have a blood sample at baseline and after 2 years. Parents of newly recruited subjects will also have abbreviated IQ testing.

Official Title
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Type 1 Diabetes and the Brain in Children: Metabolic Interventions. Protocol #1: Longitudinal Assessment

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for T1 Diabetes Group: Diabetes diagnosed after age 6 months Gestational age >34 weeks, birth weight >2kg Inclusion Criteria for Healthy Control Group: Normal HbA1C and fasting blood glucose Negative diabetes auto-antibodies (those that are siblings of T1D patients) Gestational age >34 weeks, birth weight >2kg Exclusion Criteria for Both Groups: History of mental retardation, language or learning disability Known genetic or medical problem that could impair brain development Abnormality of the brain/nervous system, visual or hearing problem History of seizures not associated with fever Previous inpatient psychiatric treatment Unable to have a MRI of the head due to metal appliances

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Children with Type 1 Diabetes<br>Subjects with T1 diabetes will undergo a physical exam and blood test as well as structural and functional brain MRI, neurocognitive testing and wear a continuous glucose monitor every 3 months for 24 months. | Other: Observational<br> <br> |
| Healthy Controls<br>Subjects will undergo a physical exam and blood test as well as structural and functional brain MRI at baseline and after 24 months. | Other: Observational<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in total and regional gray and white matter volumes and white matter microstructure. | Structural MRIs of children with T1 diabetes will be compared to age- and sex-matched, non-diabetic healthy controls. We will investigate whether these changes are associated with measures of glycemic control and neurocognitive metrics as these children grow and progress through puberty. The present cohorts (T1D and controls) of young children will be followed for 2 more years with similar studies repeated 2 years apart. Overall glycemic profiles will continue to be obtained every 3 months longitudinally between scans with CGM and HbA1c for children with Type 1 Diabetes. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of activation of frontal-parietal networks and functional connectivity of resting state networks using blood oxygen level dependent (BOLD)-functional MRI. |  | 2 years | 
| Changes in Neurocognitive metrics including IQ as well as executive and visual-spatial memory. | We will perform neurocognitive metrics reflecting frontal, parietal-occipital and hippocampal function. Children with T1D will be followed longitudinally and compared with controls to determine whether these differences are associated with measures of glycemic control. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Brain Growth and Development, Cognition, Children, Continuous Glucose Monitoring, Functional MRI