Molecules Associated With the Presence and Severity of Nonalcoholic Fatty Liver Disease (NAFLD)

Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated With the Presence and Severity of Nonalcoholic Fatty Liver Disease

Non-invasive diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) remain unmet medical needs. Aim of this study is to investigate the blood levels of three hormonal systems related to obesity, insulin resistance and inflammation in patients with different stages of NAFLD, in order to identify potential diagnostic markers.

Study aim: To compare the blood levels of: a) proglucagon-derived hormones (glucagon-like peptide [GLP]-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]), b) follistatins-activins (follistatin-like (FSTL)3, activin B), c) IGF axis (insulin-like growth factor (IGF)-1, total and intact IGF binding protein (IGFBP)-3 and IGFBP-4, in 18 individuals with early stage NAFLD vs. 14 controls To explore the levels of GDF-15, total and intact, in NAFLD versus obese controls (OC) at baseline and during oral glucose tolerance tests (OGTTs)

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Nonalcoholic Fatty Liver

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 54642
    • Hippokration General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects from the Second Propaedeutic Department of Internal Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Greece

Description

Inclusion Criteria:

• Individuals with liver ultrasound imaging
• Adults

Exclusion Criteria:

• The presence of any secondary cause of fatty liver, such as viral, alcoholic, autoimmune and drug-induced hepatitis.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
NAFLD
Non-NAFLD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proglucagon-derived hormones	glucagon-like peptide GLP-1 (pg/ml)	baseline
Proglucagon-derived hormones	glucagon-like peptide GLP-2 (pg/ml)	baseline
Proglucagon-derived hormones	glicentin (pmol/l)	baseline
Proglucagon-derived hormones	oxyntomodulin (pg/ml)	baseline
Proglucagon-derived hormones	glucagon (pg/ml)	baseline
Proglucagon-derived hormones	major proglucagon fragment [MPGF]) (ng/ml)	baseline
Follistatins-activins	follistatin-like (FSTL)3 (ng/ml)	baseline
Follistatins-activins	activin B (pg/ml)	baseline
IGF axis	insulin-like growth factor (IGF)-1 (ng/ml)	baseline
IGF axis	total and intact IGF binding protein (IGFBP)-3 and IGFBP-4 (ng/ml)	baseline
Liver ultrasound	Estimation of echogenicity, hepatomegaly, and intra-hepatic vascular blurring (1: Intermediate, 1-2: Intermediate to Moderate, 2: Moderate, 3: Severe)	baseline
GDF-15	Total and intact Growth differentiation factor 15 (pg/mL)	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)	BMI is calculated as weight in kilograms divided by height in meters squared.	baseline
Biochemical parameters	Glucose (mg/dl)	baseline
Biochemical parameters	serum aspartate transaminase (AST) (U/L), ALT (U/L)	baseline
Biochemical parameters	gamma-glutamyltransferase (GGT) (U/L)	baseline
Biochemical parameters	total cholesterol (mg/dl), triglycerides (mg/dl) and high density lipoprotein-cholesterol (HDL-C) (mg/dl), low density lipoprotein-cholesterol (LDL-C) (mg/dl)	baseline
Biochemical parameters	insulin (μU/ml)	baseline
Metabolomics and lipidomics analysis	Measured with nuclear magnetic resonance spectroscopy (NMR) by Labcorp (Morrisville, USA).	baseline

Collaborators and Investigators

• Sponsor: Hippocration General Hospital

Publications and helpful links

General Publications

• Polyzos SA, Perakakis N, Boutari C, Kountouras J, Ghaly W, Anastasilakis AD, Karagiannis A, Mantzoros CS. Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e390-400. doi: 10.1210/clinem/dgz172.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2017
• Primary Completion (Actual): May 30, 2017
• Study Completion (Actual): May 30, 2017

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Estimate): December 26, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Liver Diseases; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: Hippocratio_2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No