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

NCT ID: NCT01725035

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2022-08-10

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.

Detailed Description

In this study obese youths, adolescents and young adults (12-30 years) will undergo MRI (magnetic resonance imaging) measurement of liver lipid content to determine hepatic fat content. They will undergo a sugary drink (75 grams of glucose and 25 grams of fructose) challenge and Hepatic de novo lipogenesis will be determined as the incorporation of deuterium, from deuterium labeled water (D2O), into plasma triglycerides. Subjects will undergo a 6 hours study assessing de novo lipogenesis, an oral glucose tolerance test, dual energy x-ray absorptiometry, magnetic resonance imaging, and Euglycemic-Hyperinsulinemic Clamp.

This study record has been re-opened in 2019 and updated to reflect any changes having remained open since its inception with the Yale University IRB and also having obtained additional funding though NIDDK.

Conditions

Hepatic Steatosis; Fatty Liver

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Fatty liver

No interventions assigned to this group

Non Fatty liver

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sonia Caprio, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Nicola Santoro, M.D./Ph.D,

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

11CRP5620013

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1R01DK114504-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1008007192

Identifier Type: -

Identifier Source: org_study_id