Fructose: Substrate, Stimulus, or Both?

Touro University, California35 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Insulin Resistance Insulin Sensitivity Pre Diabetes

Interventions

High fructose, fructose labeled mealOTHER

Liquid meal containing high fructose (16% of energy), labeled with 2-13C fructose

High fructose, pyruvate labeled mealOTHER

Liquid meal containing high fructose (16% of energy), labeled with 2-13C pyruvate

Low fructose, fructose labeled mealOTHER

Liquid meals containing low fructose (6% of energy), labeled with 2-13C fructose

Eligibility

Sex: ALLMin age: 20 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Touro University California

Vallejo, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 6 hours

Rate of appearance of UDP-glucose

An estimate of hepatic glycogen flux measured by administration of D1 galactose and acetaminophen

Time frame: 6 hours

Rate of appearance of blood glucose from gluconeogenesis

Measured by the dilution method of labeled glucose

Time frame: 6 hours

Secondary Outcomes

Serum triglyceride concentration

Fasting and postprandial serum triglyceride levels

Time frame: 6 hours

Serum glucose concentration

Fasting and postprandial serum triglyceride levels

Time frame: 6 hours

Serum lactate concentration

Fasting and postprandial serum lactate levels

Time frame: 6 hours

Serum insulin concentration

Fasting and postprandial insulin levels

Time frame: 6 hours

Serum free fatty acid concentration

Fasting and postprandial fatty acid levels

Time frame: 6 hours

Enteral (chylomicron) fractional de novo lipogenesis (DNL)

Data from ClinicalTrials.gov

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