Fructose: Substrate, Stimulus, or Both?
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 35
- Locations
- 2
- Primary Endpoint
- Hepatic fractional de novo lipogenesis in triglyceride rich lipoprotein (TRL)
Study Overview
Brief Summary
This objective of this study is to use sensitive methodology under controlled conditions to investigate the mechanisms by which fructose consumption contributes to excess fatty acid synthesis and elevations in blood glucose levels following consumption of meals containing fructose.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 20 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Body Mass Index 22 to 35 kg/m2
- •Prediabetic (HbA1c 5.7% to 6.5%) or hyperinsulinemic (fasting insulin ≥12 µIU/mL) but non-diabetic (fasting glucose <126mg/dL and HbA1c < 6.5%) ; or normal control (fasting insulin <10 µIU/mL, fasting glucose <100 mg/dL, and HbA1c < 5.7%)
Exclusion Criteria
- •Pregnancy or lactation within the past six months
- •Type 1 or 2 diabetes mellitus
- •History of liver disease or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2x the upper limit of normal (ULN);
- •Fasting triglyceride or total cholesterol levels above 95th percentile for age and sex;
- •Hemoglobin or hematocrit below the lower limit of normal for sex;
- •Report of hepatitis or HIV infection;
- •History of cancer, use of any anti-diabetic medications or hypolipidemic agents in the past six months;
- •History of surgical procedure for obesity;
- •Self-reported change in body weight >5% in the past six months;
- •History of other conditions known to affect insulin sensitivity and lipid metabolism;
- •Known intolerance to acetaminophen or components of the liquid test meals.
Arms & Interventions
High fructose meal, with pyruvate label
2-13C pyruvate incorporated into a meal with high fructose content
Intervention: High fructose, pyruvate labeled meal (Other)
Low fructose meal, with fructose label
2-13C fructose incorporated into a meal with low fructose content
Intervention: Low fructose, fructose labeled meal (Other)
High fructose meal, with fructose label
2-13C fructose incorporated into a meal with high fructose content
Intervention: High fructose, fructose labeled meal (Other)
Low fructose meal, with pyruvate label
2-13C pyruvate incorporated into a meal with low fructose content
Intervention: Low fructose, pyruvate labeled meal (Other)
Outcomes
Primary Outcomes
Hepatic fractional de novo lipogenesis in triglyceride rich lipoprotein (TRL)
Time Frame: 6 hours
Measured by the detection of 13C carbons in TRL-palmitate from administered 13C labeled pyruvate or 13C labeled fructose.
Rate of appearance of UDP-glucose
Time Frame: 6 hours
An estimate of hepatic glycogen flux measured by administration of D1 galactose and acetaminophen
Rate of appearance of blood glucose from gluconeogenesis
Time Frame: 6 hours
Measured by the dilution method of labeled glucose
Secondary Outcomes
- Serum glucose concentration(6 hours)
- Serum free fatty acid concentration(6 hours)
- Enteral (chylomicron) fractional de novo lipogenesis (DNL)(6 hours)
- Serum triglyceride concentration(6 hours)
- Serum lactate concentration(6 hours)
- Serum insulin concentration(6 hours)
- Hepatic (VLDL) fractional de novo lipogenesis (DNL)(6 hours)
- Extrasplanchnic fructose(6 hours)
- Whole body fructose oxidation(6 hours)