Regulation of Endogenous Glucose Production by Central KATP Channels

Eligibility Criteria

• * Age: 21-70 years old
• * Body Mass Index (BMI) under 35
• * Negative drug screen
• * Normal Hemoglobin A1c (HbA1c) and fasting glucose
• * No family history of diabetes among first degree relatives (e.g., mother, father)
• * Age: 21-70 years old
• * BMI under 35
• * Stable and moderate-to-poor glycemic control (HbA1c: 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).
• * Age: Under 21 or over 70 years ol
• * BMI: \>35 for Type 2 Diabetes (T2D) and Non-Diabetic (ND) subjects
• * Blood pressure \>150/90 or \<90/60 on more than one occasion
• * Severe polydipsia and polyuria (in subjects with T2D). Since polydipsia and polyuria are common symptoms of T2D, the distinction "severe" denotes that the subject indicates a worsening in the symptoms and/or an experience of discomfort related to the symptoms at the time of screening and/or at the time of withdrawal from the medications
• * Urine microalbumin: \>300 mg/g of creatinine (in subjects with T2D)
• * Uncontrolled hyperlipidemia defined as Triglycerides (TG) \> 400 mg/dL and/or Total Cholesterol \>300 mg/dL
• * Clinically significant liver dysfunction including thrombocytopenia (platelets \<100,000/uL), anemia (as below), hypoalbuminemia (\<3.5 g/dL), coagulopathy (INR \> 1.5), and/or liver enzymes more than 3 times the upper limit of normal
• * Clinically significant kidney dysfunction, Glomerular Filtration Rate (GFR): \<60 mg/dL
• * Clinically significant anemia Prospective subjects with hemoglobin below the lower limit of 12 g/dl for for men and 11 g/dL for women will be assessed with history and physical exam to rule out clinically significant anemia, defined as an individual with symptoms (e.g., fatigue, weakness, shortness of breath, palpitations), signs (pallor, brittle nails etc.), or currently under treatment for anemia. In the absence of a documented hemoglobin decrease or iron deficiency, subjects will not be excluded
• * Clinically significant leukocytosis or leukopenia
• * Clinically significant thrombocytopenia or thrombocytosis
• * Coagulopathy
• * Urine drug screen positive for any of the following: amphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, oxycodone, phencyclidine (PCP). Amphetamines, oxycodone, opiates, methadone, and benzodiazepines have been shown to affect glucose metabolism (increased glycemia, increased fasting insulin levels, delayed insulin response to food ingestion, insulin deficiency). As the drug test available in the Clinical Research Center (CRC) is a 7-drug panel, we cannot specifically choose which drugs are screened for. Additionally, in the interest of selecting patients on the basis of their reliability and dependability, we would like to exclude participants using illicit drugs. Occasional use of cannabis (once or twice per week) is not an exclusion factor. If the test is read as "indeterminate" it will be repeated at the bedside and an additional sample will be sent to the lab. Decision to enroll subject that day prior to results from lab being available will be decided on a case-by-case basis, i.e., when all previous drug testing had been negative and clinical suspicion is very low
• * Urinalysis: Clinically significant abnormalities
• * Clinically significant electrolyte abnormalities
• * Smoking \>10 cigarettes/day
• * Alcohol: Men \>14 drinks/week or \>4 drinks/day, Women \>7 drinks/week 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 (if euthyroid on thyroid hormone replacement - if such history free thyroxine (fT4) and Thyroid Stimulating Hormone (TSH) will be checked)
• * 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 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