Hepatic De Novo Lipogenesis (DNL)in the Pathogenesis of Hepatic Steatosis in Obese Youth

NCT01725035 | Completed

• 3 other identifiers: 100800719211CRP56200131R01DK114504-01A1
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Nonalcoholic Fatty Liver Disease (NAFLD) is becoming the most common cause of liver disease in pediatrics, but little is known about its pathophysiology in children. While studies in obese adults with hepatic steatosis have described an increased hepatic de novo lipogenesis (DNL) depending on the diet, there are no studies exploring the mechanisms by which excess hepatic triglycerides increases in obese youths, thus explaining the accompanying dyslipidemia and the metabolic syndrome. The central hypothesis of this study is that hepatic conversion of carbohydrates to lipid (DNL) is enhanced and associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis. The overall goal is to examine whether hepatic DNL is increased in obese youths with steatosis compared to matched controls without steatosis. Hypotheses: Hepatic conversion of carbohydrates to lipid (DNL) is enhanced and is associated with accumulation of excess liver fat, dyslipidemia and hepatic insulin resistance in obese youths with hepatic steatosis.

Conditions

Hepatic Steatosis; Fatty Liver

Keywords

De Novo Lipogenesis; Fatty Liver; Hepatic Steatosis; Gene variants

Outcome Measures

Primary Outcomes (1)

• de novo lipogenesis response to high carbohydrate meal in obese kids with fatty liver

  Study visit 3

Secondary Outcomes (1)

• de novo lipogenesis response to high carbohydrate meal in obese kids without fatty liver

  Study visit 3

Study Arms (2)

Fatty liver

Non Fatty liver

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The majority of the research subjects will be recruited from the Yale Pediatric Obesity Clinic and the Endocrine Clinic. Following the oral glucose tolerance test (OGTT):normal glucose tolerant if plasma glucose at two hours is \<140 mg/dl and impaired glucose tolerant if plasma glucose is ≥140 mg/dl. All subjects must be in good general health, have a normal medical history and physical exam, and have no endocrinopathies or other diseases that might affect glucose metabolism. They will not be on any medications that are known to alter glucose or insulin metabolism or certain psychiatric medications. Subjects determined to be eligible will receive a MRI to determine Hepatic Fat Content. Subjects will agree to genetic testing to determine genotype.

You may qualify if:

• Cases will meet the following criteria:
• BMI higher than 75th percentile
• Hepatic fat fraction (the amount of fat into the liver) greater or equal than 5.5%
• Absence of any endocrinopathy
• Absence of any therapy with medication known to alter glucose metabolism
• Controls will meet the following criteria:
• BMI higher than 75th percentile
• Hepatic fat fraction (the amount of fat into the liver) lower than 5.5%
• Absence of any endocrinopathy
• Absence of any therapy with medication known to alter glucose metabolism
• Absence of any therapy with medication known to alter glucose metabolism

You may not qualify if:

• BMI under the 75th percentile
• Hepatic fat fraction (the amount of fat into the liver) less than 5.5%
• Absence of any endocrinopathy
• Any therapy with medication known to alter glucose metabolism
• Controls will meet the following criteria:
• BMI under the 75th percentile
• Hepatic fat fraction (the amount of fat into the liver) greater than or equal to 5.5%
• Any endocrinopathy
• Any therapy with medication known to alter glucose metabolism

Sponsors & Collaborators

• Yale University: lead
• American Heart Association: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum

MeSH Terms

Conditions

Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Sonia Caprio, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

• Nicola Santoro, M.D./Ph.D,

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2012
• First Posted: November 12, 2012
• Study Start: December 1, 2010
• Primary Completion: August 10, 2022
• Study Completion: August 10, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-06

Locations

US (1)