Type 2 Diabetes and the Brain in Adolescents

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.

Inclusion Criteria:

Type 2 Diabetes:

- BMI ≥85th percentile

- A1c ≥ 8%

- Pubertal

Healthy Controls:

- BMI ≥85th percentile for Obese Controls

- BMI < 85th percentile for Lean Controls

- Pubertal

- Normal A1c & Fasting glucose

Exclusion Criteria:

- Significant developmental delay or learning disability

- Significant visual or auditory deficits

- Born <34 weeks gestation

- Neurologic disease

- Psychiatric disease requiring inpatient treatment

- Significant head trauma

- Malignancy

- Pregnancy

- Weight > 350lb (MRI weight limit)

- Metal in the body (including dental braces)