Fructose-induced Hepatic De Novo Lipogenesis in Adolescents With Obesity

NCT03567837 | Terminated

• 1 other identifier: 180401921
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

In the U.S., dietary fructose has increased in parallel with the increase in obesity and may promote the development of diabetes and other chronic diseases. The largest source of dietary fructose is sweetened beverages that are consumed by adolescents more than any other age group. This protocol will compare the rates of hepatic de novo lipogenesis (DNL), a process in the liver that changes sugar into fat, in two groups of obese adolescents - one with prediabetes and the other, metabolically healthy. Blood will be sampled before and hourly for 3 hours after the consumption of a fructose-containing beverage. We hypothesize that the pre-diabetic group will show greater DNL in response to fructose. This would support other evidence that increased fructose-induced hepatic DNL is an early mechanism linking dietary sugar to the adverse metabolic sequelae of obesity, including diabetes, fatty liver, dyslipidemia and coronary disease.

Conditions

Adolescent Obesity

Outcome Measures

Primary Outcomes (1)

• Increase in VLDL TG palmitate

  In the 2 study groups: a comparison of the increase in VLDL TG palmitate over 3 hours after ingestion of a beverage made with fructose and glucose. after an oral challenge of fructose+glucose

  Three hours

Secondary Outcomes (1)

• Correlation of the increase in VLDL TG palmitate and markers of carbohydrate and fatty acid metabolism

  Three hours

Study Arms (2)

Obese Metabolically Healthy

ACTIVE COMPARATOR

Intervention: Oral challenge of Fructose+Glucose Beverage 1:1, 3g/kg

Other: Fructose + Glucose Beverage

Obese Pre-diabetes

EXPERIMENTAL

Intervention: Oral challenge of Fructose+Glucose Beverage 1:1, 3g/kg

Other: Fructose + Glucose Beverage

Interventions

Fructose + Glucose Beverage OTHER

The intervention is an oral sugar challenge with blood sampling over three hours.

Obese Metabolically Healthy; Obese Pre-diabetes

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 12-21 years old.
• BMI percentile \>95th and \<140th percentile of the 95th, maximum weight 110 kg.
• Group 1: HbA1C \<5.7% and no history of fasting hyperglycemia (glucose greater or equal to100 mg/dL and/or HbA1C greater or equal to 5.7%), sustained hypertension (\>95th percentile) or abnormal lipids (LDL cholesterol \<130 mg/dL, TG \<130 mg/dL, HDL-C \>40 mg/dL).
• Group 2: HbA1C greater or equal to 5.7 to 6.49%
• Pubertal or post- pubertal stage (pre-pubertal excluded).
• Willing and able to stop fish oil, fiber supplement, other non-prescribed vitamins/supplements for 1 week prior to study visit.
• Willing to not drink alcohol for at least 48 hours before the study visit.
• Willing to refrain from vigorous exercise the day before the study visit.

You may not qualify if:

• Diabetes (fasting blood glucose greater or equal to126 mg/dL, and/or HbA1C \>6.5% and/or history of a 2 hour oral glucose tolerance test (OGTT) \>200 mg/dL).
• Triglycerides \>500 mg/dL, LDL cholesterol \>160 mg/dL.
• Medications affecting lipid or glucose metabolism, including hormonal contraceptives.
• Liver disease or intestinal dysfunction. Serum glutamate oxaloacetate and/or serum glutamate pyruvate \< 2x upper limit normal is permitted if there is no diagnosis of liver disease by a gastroenterologist.
• Weight loss \>10% in past 6 months.
• Cigarette smoking.
• Alcohol or drug abuse.
• Systemic illness, including polycystic ovary disease and acute infections within two weeks of study visits.
• Anemia.
• Pregnancy or breast feeding.
• Psychiatric illness.
• Extreme diet or level of physical activity.
• Fructose intolerance.
• Implanted electronic devices (bioimpedance measurement).
• Any other condition, which in the opinion of the principal investigator, should prohibit participation in the study.

Sponsors & Collaborators

• The Rogosin Institute: lead
• Weill Medical College of Cornell University: collaborator
• University of Missouri-Columbia: collaborator

Study Sites (1)

Weill Cornell Medicial College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Pediatric Obesity

Interventions

Fructose

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Lisa Hudgins, MD

  The Rogosin Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: June 26, 2018
• Study Start: August 13, 2018
• Primary Completion: June 4, 2019
• Study Completion: June 4, 2019
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)