Use of Functional MRI to Assess Functional Hypothalamic Activation in Response to Diazoxide

In this study, the investigators will use functional magnetic resonance imaging (fMRI), a
method of imaging the blood flow to parts of the brain, to observe the activity of
metabolically-relevant areas of the brain by activating Katp channels in healthy participants
and in participants with type 2 diabetes (T2D).

All participants will be screened prior to study enrollment. Eligible participants will have
2 day-long study visits (one day in which the brain will be imaged before and after receiving
diazoxide (Katp channel activator) and one day in which the brain will be imaged before and
after placebo). Each study day will include up to 3 MRI scans per study visit.

fMRI is a technique for measuring and mapping brain activity that is noninvasive and safe.
This technique relies on the fact that cerebral blood flow and neuronal activity are coupled.
To assess the effect of diazoxide on activation of hypothalamus and other brain areas in
healthy control and T2D subjects, fMRI will be performed at baseline and at 2-hour intervals
following administration of diazoxide or placebo.

Inclusion Criteria:

- Type 2 Diabetes (T2D)

- Age: Between 21 and 65 y.o.

- BMI: <35

- A1c 8.0-12.0%

- Negative drug screen

- Not suffering from proliferative retinopathy, significant diabetic renal disease
or symptomatic neuropathy (including cardiovascular and gastrointestinal
autonomic dysfunction

- Healthy (ND)

- Age: Between 21 and 65 y.o.

- BMI: <30

- Negative drug screen

- No family history of diabetes among first-degree relatives (mother, father)

Exclusion Criteria:

- Age: Under 21 or over 65 y.o.

- BMI: >35 for T2D and >30 for ND

- Hypertension

- Severe polydipsia and polyuria

- Uncontrolled hyperlipidemia

- Clinically significant liver dysfunction

- Clinically significant kidney dysfunction

- Anemia

- Leukocytosis or leukopenia

- Thrombocytopenia or thrombocytosis

- Coagulopathy

- Positive urine drug screen

- Urinalysis: Clinically significant abnormalities

- Clinically significant electrolyte abnormalities

- Smoking >7 cig/day

- Alcohol: Men >14 drinks/wk or > 4drinks/day, Women > 7 drinks/wk or > 3 drinks/day

- History of chronic liver disease, active hepatitis infection, HIV/AIDS, chronic kidney
disease (stage 3 or greater), active cancer, cardiovascular disease or other heart
disease, systemic rheumatologic conditions, seizures, bleeding disorders, muscle
disease

- Surgeries that involve removal of endocrine glands except for thyroidectomy

- Pregnant women

- Subject enrolled in another study less than one month prior to the anticipated start
date of the proposed study

- Family history: family history of premature cardiac death

- Allergies to medication administered during study

- Uncontrolled psychiatric disorders

- Perimenopausal women who are experiencing/have experienced hot flashes

- Any contraindications for MRI: presence of any non-MRI compatible implants including
pacemaker, aneurysm clip, cochlear implant, neurostimulator; history of eye injury
with metal; history of ever being a metal worker; history of gunshot wounds or any
other imbedded metal objects; history of claustrophobia or prior episodes of
significant anxiety or discomfort while obtaining an MRI.

- Any condition which in the opinion of the PI makes the subject ill-suited for
participation in the study