Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia

• INCLUSION CRITERIA:

Cohort 1

• Males and females aged 18 to 65 years.

• BMI 18.5 26.9 kg/m^2 .

• Able to understand the study procedures and provide written consent, and willing to comply with all scheduled follow-up visits and assessments.

• Normotensive and not on antihypertensive medications, blood pressure 90-129/60-84.

• Not on glucose-lowering or lipid-lowering medications.

• At screening, laboratory values meet all of the following:

  • HbA1c < 5.7%,

  • Fasting triglycerides < 150 mg/dL

  • LDL < 100 mg/dL

    7. Liver fat < 2%.

Cohort 2

• Males and females aged 18 to 65 years.

• BMI > 26.0 to < 36.0 kg/m2.

• Able to understand the study procedures and provide written informed consent, and willing to comply with all scheduled follow-up visits and assessments.

• At screening, laboratory values meet all of the following:

  • HbA1c <= 7.5%
  • Fasting triglycerides < 500 mg/dL
  • LDL < 190 mg/dL

• Willing to discontinue oral glucose-lowering medications (metformin) and oral lipidlowering medications for 4 to 10 weeks prior to the inpatient visit, if applicable.

• Liver fat < 2%.

EXCLUSION CRITERIA:

• Women who are pregnant or currently breastfeeding.
• Subjects younger than 18 years old. This age group has a broad spectrum of hormonal profiles due to development and puberty, which significantly increases the heterogenicity of study subjects.
• Subjects older than 65 years. This age group has significantly increased risk of cardiovascular diseases. To minimize the risk from temporarily suspending lipid- and glucose-lowering medications and the stress from serial blood draws, these individuals are excluded.
• Heavy alcohol use within past 12 months (males: >2 drinks per day or >14 drinks per week; females: >1 drink per day or >7 drinks per week).
• Current smoker, or former smoker who quit smoking less than 15 years ago.
• Subjects with weight changes greater than 20% of baseline body weight (self-reported or documented within past 12 months) over the past 3 months at outpatient visit 1, or change from outpatient visit 1 during screening.
• Subjects with lactose intolerance who are unwilling to take lactase.
• Subjects with type 1 diabetes.
• Subjects with hemoglobin <11 g/dL or hematocrit <33%.
• Subjects with clinically significant abnormal liver function test results.
• Subjects with liver fat >= 2% on abdominal MRI.
• Subjects with a history of pancreatitis, diabetes ketoacidosis, hyperosmolar hyperglycemic state, advanced atherosclerosis, cardiovascular diseases, kidney diseases, or liver diseases.
• Subjects with fat malabsorption, including a history of gastrointestinal surgery, pancreatic insufficiency, inflammatory bowel disease, celiac disease, moderate-to-severe irritable bowel syndrome, or pathologic mutations impacting lipoprotein metabolism.
• Subjects on glucocorticoids for more than 1 week (not including topical glucocorticoids) within past 3 months.
• Subjects with HIV.
• Subjects with uncontrolled psychiatric and/or behavioral disorders.
• Subjects taking diabetes medications other than metformin.
• Subjects with anticipated surgery during the study period.
• Subjects with severe medication-resistant claustrophobia.
• Subjects who are unwilling to stop medications, vitamins, and/or dietary supplements that investigators have requested to be held.
• Subjects participating in any other clinical study without informing investigators.
• Any other reason or clinical condition that the investigators judge would interfere with study participation and/or be unsafe for the participant or staff member.