Fructose Intestinal Gluconeogenesis

N/ANot Yet RecruitingNCT07209202

Touro University, California40 enrolled

Overview

This study will test the hypothesis that within a defined range of fructose intake, the ability to convert fructose to glucose (via gluconeogenesis) in the small intestine plays a protective role for the liver, shielding it from the deleterious effects of fructose. We will investigate whether this protective effect of the intestine is impaired in individuals with obesity.

Qualified participants will undergo a sugar tolerance test at baseline and then randomized to undergo four separate outpatient tracer/feeding studies in a crossover fashion. After an overnight fast, a six-hour fed tracer study will be initiated, during which participants will consume liquid meals containing stable isotopes at regular intervals and receive other isotopes intravenously. Meal composition will differ only by fructose content (High vs. Low) and tracer (oral vs. intravenous 13C-labeled fructose). Blood and urine samples will be collected frequently throughout the study. Each visit will be performed approximately three weeks apart. Vital signs and anthropometrics will be measured at each clinic visit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Healthy Participants Obese But Otherwise Healthy Participants

Interventions

High fructose mealOTHER

Liquid meals containing 55% total carbohydrate (16% fructose), 30% fat, 15% protein.

Low fructose mealOTHER

55% total carbohydrate (6% fructose), 30% fat, 15% protein.

13C labeled fructose, oralOTHER

Tracer amount of 13C labeled fructose administered orally in the meals.

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: * BMI 30 to 38 kg/m2 (obese group) or BMI 19 to 25 kg/m2 (lean group) Exclusion Criteria: * Pregnancy or lactation within the past six months; * Type 1 or 2 diabetes mellitus (including fasting glucose ≥126 mg/dL, HgbA1c ≥6.5%); * History of liver disease or AST and ALT 2x above the upper limit of normal; * Fasting triglyceride \> 300 mg/dl; total cholesterol levels above the 95th percentile for age and sex; * Hemoglobin (Hgb) \<12.5g/d or hematocrit\<3x Hgb value; * Report of HIV or hepatitis B or C infection; * History of cancer, other than basal cell or squamous cell carcinoma or kidney disease stage 3 or higher or patients currently on dialysis; * Use of any anti-diabetic medications or hypolipidemic agents in the past six months; * History of surgical procedure for obesity; * Change in body weight \>5% in the past six months (by self-report); * History of other conditions known to affect insulin sensitivity and lipid metabolism (e.g., polycystic ovary syndrome), history of galactosemia, hereditary fructose intolerance, or who test positive for fructose malabsorption at screening; * Known intolerance to acetaminophen.

Outcomes

Primary Outcomes

Fru-GNG

Total amount of fructose converted to glucose

Time frame: 6 hours

Fru-hGNG

Amount of fructose converted to glucose in the liver

Time frame: 6 hours

Fru-iGNG

Amount of fructose converted to glucose in the intestine

Time frame: 6 hours

De novo lipogenesis (DNL)

Percent of newly synthesized palmitate

Time frame: 6 hours

Central Contacts

Sally Chiu, PhD

CONTACT

707-638-5404 schiu2@touro.edu

Lisa Johnson, RN

CONTACT

ljohnson19@touro.edu

Data from ClinicalTrials.gov

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