Overview
Type 2 diabetes affects the ability of the body to process glucose (sugar). Under fasting conditions, the liver is able to make sugar to maintain glucose levels in an important process called endogenous glucose production (EGP). Previous studies suggest that the central nervous system (CNS), including the brain, helps to regulate levels of glucose in the body by communicating with the liver. This process can be impaired in people with type 2 diabetes, and can contribute to the high level of glucose seen in these individuals.
The purpose of this study is to understand how activating control centers of the brain with a medication called diazoxide can affect how much glucose (sugar) is made by the liver. This is particularly important for people with diabetes who have very high production of glucose, which in turn can lead to diabetes complications.
Description
In this study, the investigators will study healthy participants and participants with type 2 diabetes through a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Endogenous glucose production (a measure of the body's production of sugar) will be measured in patients given diazoxide (a medication that activates potassium channels in the brain that may affect glucose production in the liver through brain-liver signaling), compared with when a placebo is given. This study will also investigate whether lowering free fatty acid levels which may help improve the the body's ability to regulate glucose levels.
Eligibility
Inclusion Criteria:
For healthy participants:
- Age: 21-70 y.o.
- BMI under 35
- Negative drug screen
- Normal A1C and fasting glucose
- No family history of diabetes among first degree relatives (eg. mother, father)
For T2D participants:
- Age: 21-70 y.o.
- BMI under 35
- A1c 8.0-12.0%
- Negative drug screen
- Not suffering from a previously diagnosed proliferative retinopathy, significant diabetic renal disease or severe neuropathy (including cardiovascular and gastrointestinal autonomic dysfunction).
Exclusion Criteria:
- Age: Under 21 or over 70 y.o.
- BMI: >35
- Blood pressure >150/90 or <90/60 on more than one occasion
- Severe polydipsia and polyuria
- Urine microalbumin: >300 mg/g of creatinine (in subjects with T2D)
- Uncontrolled hyperlipidemia
- Clinically significant liver dysfunction
- Clinically significant kidney dysfunction
- Clinically significant anemia
- Clinically significant leukocytosis or leukopenia
- Clinically significant thrombocytopenia or thrombocytosis
- Coagulopathy
- Positive urine drug screen
- Urinalysis: Clinically significant abnormalities
- Clinically significant electrolyte abnormalities
- Smoking >10 cig/day
- Alcohol: Men >14 drinks/wk or >4 drinks/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, besides those done by our group
- Family history: family history of premature cardiac death
- Allergies to medication administered during study
- Uncontrolled psychiatric disorders
- Any condition which in the opinion of the PI makes the subject ill suited for participation in the study