This study evaluates differences in brain function and cognitive performance in adolescents with type 2 diabetes (T2D) compared to non diabetic controls (both obese and lean) and correlates these changes with obesity, insulin resistance, and glycemic control in youth with T2D.
This is a cross-sectional study examining neurocognitive function and brain activity in resting state and during working memory and executive function tasks using blood oxygen level dependent (BOLD) functional MRI (fMRI) during hyperinsulinemic euglycemic and hyperglycemic clamps in obese adolescents with T2D compared to non-diabetic obese and lean controls. The investigators will measure glycemic control (acute hyperglycemia during clamps and glycemic variability) and insulin resistance to examine their association with neurocognitive metrics and brain functional activity. There will be one screening visit and three study visits for subjects with T2D. One visit will consist of neurocognitive testing and dual energy X-ray absorptiometry (DEXA) of the whole body to assess body composition including fat mass. In the other two visits, subjects with T2D will undergo normal and high glucose clamps during fMRI. Obese and lean control subjects will have one screening visit and two study visits, one for neurocognitive testing and DEXA and another for fMRI without glucose clamps. All subjects will have a blood sample obtained at the screening visit. Only adolescents with type 2 diabetes will wear a continuous glucose monitor (CGM) for 6 days prior to neuroimaging to determine glycemic variability. A1C will be assessed at baseline. Parents of subjects will also have abbreviated IQ testing.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
18
Subjects with T2D will receive IV Dextrose infusion to maintain plasma glucose at \~250 mg/dL during fMRI.
Subjects with T2D will receive IV Dextrose and Insulin infusion to maintain plasma glucose at approximately 90 mg/dL during fMRI.
Nemours Children's Health System
Jacksonville, Florida, United States
Brain Activity using functional MRI (fMRI)
The investigators will examine functional connectivity of brain networks during cross sectional resting-state and task-related (working memory and response inhibition) BOLD-fMRI activation. fMRI activation in adolescents with T2D will be compared to age- and sex- matched, non-diabetic, healthy lean and obese controls.
Time frame: Baseline
Neurocognitive battery metrics including IQ as well as executive function and visual-spatial memory
The investigators will evaluate cognitive performance by examining test scores from neurocognitive metrics which reflect global IQ, spatial recognition, episodic memory, executive function (includes response inhibition, working memory), academic achievement, and processing speed. Adolescents with T2D will be compared to controls to determine whether these differences are associated with glycemic control, obesity, and insulin resistance.
Time frame: Baseline
fMRI performance in relation to dysglycemia
In adolescents with T2D, the investigators will examine BOLD-fMRI brain activation in relation to acute hyperglycemia during glucose clamping, chronic hyperglycemia, glycemic variability, and insulin resistance.
Time frame: Baseline
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