Fructose: Substrate, Stimulus, or Both?

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 Overview

• Status: Recruiting
• Conditions: Insulin Resistance; Insulin Sensitivity; Pre Diabetes
• Intervention / Treatment: Other: High fructose, fructose labeled meal; Other: High fructose, pyruvate labeled meal; Other: Low fructose, fructose labeled meal; Other: Low fructose, pyruvate labeled meal

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sally Chiu, PhD; Phone Number: 707-638-5404; Email: sally.chiu@tu.edu

Study Locations

• United States
  • California
    • Vallejo, California, United States, 94592
      • Recruiting
      • Touro University California
      • Principal Investigator: Jean-Marc Schwarz, PhD
      • Contact: Jean-Marc Schwarz, PhD; Phone Number: 707-638-5456; Email: jean-marc.schwarz@tu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High fructose meal, with fructose label; 2-13C fructose incorporated into a meal with high fructose content	Other: High fructose, fructose labeled meal; Liquid meal containing high fructose (16% of energy), labeled with 2-13C fructose
Experimental: High fructose meal, with pyruvate label; 2-13C pyruvate incorporated into a meal with high fructose content	Other: High fructose, pyruvate labeled meal; Liquid meal containing high fructose (16% of energy), labeled with 2-13C pyruvate
Experimental: Low fructose meal, with fructose label; 2-13C fructose incorporated into a meal with low fructose content	Other: Low fructose, fructose labeled meal; Liquid meals containing low fructose (6% of energy), labeled with 2-13C fructose
Experimental: Low fructose meal, with pyruvate label; 2-13C pyruvate incorporated into a meal with low fructose content	Other: Low fructose, pyruvate labeled meal; Liquid meal containing low fructose (6% of energy), labeled with 2-13C pyruvate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic fractional de novo lipogenesis in triglyceride rich lipoprotein (TRL)	Measured by the detection of 13C carbons in TRL-palmitate from administered 13C labeled pyruvate or 13C labeled fructose.	6 hours
Rate of appearance of UDP-glucose	An estimate of hepatic glycogen flux measured by administration of D1 galactose and acetaminophen	6 hours
Rate of appearance of blood glucose from gluconeogenesis	Measured by the dilution method of labeled glucose	6 hours

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Touro University, California
• Investigators: Principal Investigator: Jean-Marc Schwarz, PhD, Touro University, California

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Fructose; Glucose; Lipogenesis
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Prediabetic State; Insulin Resistance
• Other Study ID Numbers: M-3018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No