Fructose: Substrate, Stimulus, or Both?

Not Applicable

Completed

• Conditions: Insulin Resistance; Pre Diabetes; Insulin Sensitivity
• Interventions: Other: High fructose, fructose labeled meal; Other: Low fructose, pyruvate labeled meal; Other: Low fructose, fructose labeled meal; Other: High fructose, pyruvate labeled meal

• Registration Number: NCT04168372
• Lead Sponsor: Touro University, California

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-15
• Study First Submitted: 2019-11-14
• Study First Submitted QC: 2019-11-15
• Study First Posted: 2019-11-19
• Primary Completion: 2024-11-20
• Study Completion: 2024-11-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High fructose meal, with fructose label	High fructose, fructose labeled meal	2-13C fructose incorporated into a meal with high fructose content
Low fructose meal, with pyruvate label	Low fructose, pyruvate labeled meal	2-13C pyruvate incorporated into a meal with low fructose content
Low fructose meal, with fructose label	Low fructose, fructose labeled meal	2-13C fructose incorporated into a meal with low fructose content
High fructose meal, with pyruvate label	High fructose, pyruvate labeled meal	2-13C pyruvate incorporated into a meal with high fructose content

Primary Outcome Measures

Name	Time	Method
Hepatic fractional de novo lipogenesis in triglyceride rich lipoprotein (TRL)	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	6 hours	An estimate of hepatic glycogen flux measured by administration of D1 galactose and acetaminophen
Rate of appearance of blood glucose from gluconeogenesis	6 hours	Measured by the dilution method of labeled glucose

Secondary Outcome Measures

Name	Time	Method
Serum glucose concentration	6 hours	Fasting and postprandial serum triglyceride levels
Serum free fatty acid concentration	6 hours	Fasting and postprandial fatty acid levels
Enteral (chylomicron) fractional de novo lipogenesis (DNL)	6 hours	Measured by the detection of 13C carbons in chylomicron-palmitate from administered 13C labeled pyruvate or 13C labeled fructose.
Serum triglyceride concentration	6 hours	Fasting and postprandial serum triglyceride levels
Serum lactate concentration	6 hours	Fasting and postprandial serum lactate levels
Serum insulin concentration	6 hours	Fasting and postprandial insulin levels
Hepatic (VLDL) fractional de novo lipogenesis (DNL)	6 hours	Measured by the detection of 13C carbons in VLDL-palmitate from administered 13C labeled pyruvate or 13C labeled fructose.
Extrasplanchnic fructose	6 hours	Calculated using total plasma fructose, plasma 2-13C fructose enrichment, and endogenous fructose production
Whole body fructose oxidation	6 hours	Measured by 13C atom % excess in exhaled breath, and VCO2 by indirect calorimetry

Trial Locations

Locations (1)

Touro University California; 🇺🇸 Vallejo, California, United States