Graded Insulin Suppression Test P&F

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 15

Inclusion Criteria

Inclusion Criteria: - Body mass index of 18-25 and 30-45 kg/m2 - Able to understand written and spoken English and/or Spanish - Fasting euinsulinemia (fasting serum insulin of 5-10 µU/mL) for reference group or hyperinsulinemia (fasting serum insulin = 13 µU mL-1) for hyperinsulinemic group on screening labs - Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations. Exclusion Criteria: - Unable to provide informed consent in English or Spanish - Unwillingness to use only bedpan or urinal to void or to refrain from non-emergent mobile device use during the GIST - Documented weight loss of = 5% of baseline within the previous 6 months - Systolic blood pressure < 90 mm Hg or > 160 mm Hg, and/or - Diastolic blood pressure < 60 mm Hg or > 100 mm Hg - Abnormal resting heart rate: < 60 or = 110 bpm - Sinus brady or tachycardia that has been worked up and considered benign by the recruit's personal physician may be permitted at the PI's discretion - Abnormal screening electrocardiogram (or if on file, performed within previous 90 d): - Non-sinus rhythm - Heart conduction blocks - Previously unknown ischaemic changes that persist on repeat EKG: - ST elevations - T-wave inversions in a vascular distribution - Hemoglobin A1c = 5.7%, and/or - Fasting plasma glucose = 100 mg/dL - Positive qualitative ß-hCG (i.e., pregnancy test) in women of childbearing potential - Positive urine drug screen, except for lawfully prescribed medications and/or marijuana, provided that participant agrees to refrain from marijuana use during the period that they refrain from alcohol. - Transaminases (AST or ALT) > 3.0 x the upper limit of normal - Total bilirubin > 1.25 x the upper limit of normal - Abnormal sodium, potassium, chloride, or bicarbonate levels that are considered potentially significant according to the clinical judgment of the PI. - Creatinine equating to estimated glomerular filtration rate < 60 mL min-1 1.73 m-2 - Hemoglobin < 10 g/dL or hematocrit < 30% - Platelet count < 100,000/µL - Women currently pregnant, measured by serum and/or urine ß-hCG - Women currently breastfeeding - History of having met any of the American Diabetes Association's definitions of prediabetic state or diabetes mellitus (i.e., overt diabetes): - Hemoglobin A1c = 5.7%, or rapid rise in documented HbA1c values causing clinical concern for evolving insulin deficiency - Plasma glucose = 100 mg/dL after 8-h fast - Plasma glucose of = 140 mg/dL at 2 h after ingestion of a 75-g glucose load - Random plasma glucose = 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state - History of gestational diabetes mellitus within the previous 5 years - Use of most antidiabetic medications within the 30 days prior to screening - Excluded: thiazolidinediones, sulfonylureas, meglitinides, DPP4 inhibitors, GLP-1 receptor agonists, SGLT2 inhibitors, amylin mimetics, acarbose, insulin - Metformin is acceptable provided that recruits meet all of the inclusion criteria at screening - Known, documented history, at the time of screening, of any of the following medical conditions: - Pancreatic pathology, including but not limited to: Pancreatic neoplasia (unless appropriately evaluated and considered benign and not producing hormones), Chronic pancreatitis, History of acute pancreatitis within the past 5 years - Cardiovascular diseases (N.B. uncomplicated hypertension is not exclusionary) - Atherosclerotic cardiovascular disease - Stable or unstable angina - Myocardial infarction - Ischaemic or hemorrhagic stroke - Peripheral arterial disease (claudication) - Use of dual antiplatelet therapy (aspirin + P2Y12 inhibitor) - History of percutaneous coronary intervention - Heart rhythm abnormalities (non-sinus) - Congestive heart failure of any New York Heart Association class - Severe valvular heart disease (e.g., aortic stenosis) - Pulmonary hypertension - Chronic kidney disease, Stage 3 or higher (estimated glomerular filtration rate < 60 mL/min/1.73 m2), of any cause - Advanced or severe liver disease, including but not limited to: - Advanced liver fibrosis, as determined by non-invasive testing - Cirrhosis of any etiology - Autoimmune hepatitis or other rheumatologic disorder affecting the liver - Biliopathy (e.g., progressive sclerosing cholangitis, primary biliary cholangitis) - Hepatocellular carcinoma - Infiltrative disorders (e.g., sarcoidosis, hemochromatosis, Wilson disease) - Gallstone disease, including: - Biliary colic (active) - History of acute cholecystitis not treated with cholecystectomy - History of other gallstone complications (e.g., pancreatitis, cholangitis) - Chronic viral illness (N.B. diagnosis based only on medical history and not by laboratory confirmation) - Hepatitis B virus (HBV), unless previously successfully eradicated with antiviral drugs that have been discontinued for at least 30 d prior to screening - Hepatitis C virus (HCV) infection, unless previously successfully eradicated with antiviral drugs that have been discontinued for at least 30 d prior to screening - Human immunodeficiency virus (HIV) infection - Active seizure disorder (including controlled with antiepileptic drugs) - Psychiatric diseases causing functional impairment that: - Are or have been decompensated within 1 year of screening, and/or - Require use of anti-dopaminergic antipsychotic drugs associated with significant weight gain/metabolic dysfunction (e.g., clozapine, olanzapine), monoamine oxidase inhibitors, tricyclic antidepressants, or lithium - Other endocrinopathies: - Cushing syndrome (okay if considered in remission after treatment, provided that no exogenous corticosteroids or other ongoing treatment are required) - Adrenal insufficiency - Primary aldosteronism - Venous thromboembolic disease (deep vein thrombosis or pulmonary embolism) or any required use of therapeutic anticoagulation - Bleeding disorders, including due to anticoagulation, or significant anemia - Active malignancy, or hormonally active benign neoplasm, except allowances for: - Non-melanoma skin cancer - Differentiated thyroid cancer (AJCC Stage I only) - Clinical concern for increased risk of volume overload, including due to medications and/or heart/liver/kidney problems, as liste

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Steady-state plasma glucose at euinsulinemia (E-SSG);Steady-state plasma glucose at hyperinsulinemia (H-SSG);Steady-state serum insulin at euinsulinemia (E-SSI);Steady-state serum insulin at hyperinsulinemia (H-SSI)

Secondary Outcome Measures

Name	Time	Method
Steady-state plasma free fatty acids (FFA) at euinsulinemia;Steady-state plasma free fatty acids (FFA) at hyperinsulinemia

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