Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals

Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals - Extended Validation.

The investigators recently demonstrated a increase in liver fat in early middle-aged LBW compared to normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). Here the investigators will further examine the Increased risk of non-alcoholic fatty liver disease in low birth weight individuals by performing a validation study.

Study Overview

• Status: Recruiting
• Conditions: Low Birth Weight; Non-Alcoholic Fatty Liver Disease

Detailed Description

An adverse fetal environment characterized by low birth weight (LBW) plays a key role in the development of type 2 diabetes (T2D). The investigators recently demonstrated a 3-fold increase in liver fat in 26 early middle-aged LBW compared to 22 normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). The investigators hypothesize that ectopic fat deposition and NAFLD is among the earliest disease manifestations and on the critical path to the development of more severe cardiometabolic disease in LBW. Here we aim to perform an extended nested case-control screening study to evaluate hepatic steatosis (NAFLD) and fibrosis in early middle-aged, non-obese LBW men and women and NBW controls. In total, 250 LBW men and women (birth weight (BW) <10% of the population) and 50 NBW controls (BW between 50-90% of the population) born at term (weeks 39-41), 34-49 years-of-age will be recruited from the National Danish Birth Registry for the nested case-control NAFLD screening study. The nested case-control NAFLD screening study will serve as a recruitment platform for a subsequent intervention study.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Charlotte Brøns, Phd; Phone Number: +4526129093; Email: charlotte.broens.01@regionh.dk

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Steno Diabetes Center Copenhagen
    • Contact: Charlotte Brøns, Phd; Phone Number: +4526129093; Email: charlotte.broens.01@regionh.dk
    • Contact: Allan Vaag, MD, PhD; Phone Number: +4520429660; Email: allan.arthur.vaag@regionh.dk
    • Principal Investigator: Charlotte Brøns, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Healthy men and women aged between 34-49 years born with a low (cases) and normal (controls) birth weight. All individuals have to be born at term in either the Copenhagen or Aarhus area.

Description

Inclusion Criteria:

• 250 healthy, men and women born with a low birth weight (birth weight (BW) <10% of the population) and 50 born with a normal birth weight controls (BW between 50-90% of the population)
• born at term (weeks 39-41)

Exclusion Criteria:

• BMI>35 kg/m2
• Disease/medication known to affect primary outcome
• Self-reported high physical activity level
• Alcohol intake above general recommendations.
• Metabolic/liver disease
• Weight gain/loss of >3 kg within the past 6 months

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fat content	Liver elastography (FibroScan) and validation by MRS	0 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fibrosis	Liver elastography, validation by MR and liver histology	0 minutes
Body composition	DEXA	0 minutes
Fasting glucose	mmol/l	0 minutes
Fasting insulin/C-peptide	pmol/l	0 minutes
Fasting lipids	mmol/l	0 minutes
Fasting liver enzymes	U/L	0 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptomics in SAT and ex vivo cultured preadipocytes	RNAseq	0 minutes
Epigenetics of SAT and ex vivo cultured preadipocytes	Genome-wide DNA methylation	0 minutes
Functional characterization of lipid accumulation	Metabolism of ex vivo differentiated preadipocytes	0 minutes
Functional characterization of lipolysis	Metabolism of ex vivo differentiated preadipocytes	0 minutes
Functional characterization of glycolysis	Metabolism of ex vivo differentiated preadipocytes	0 minutes
Functional characterization of respiration	Metabolism of ex vivo differentiated preadipocytes	0 minutes
Adipocyte size	Histology in SAT	0 minutes
Adipocyte collagen content	Histology in SAT	0 minutes
Immunohistochemical markers of fibrosis	Histology in SAT	0 minutes
Immunohistochemical markers of senescence	Histology in SAT	0 minutes
Immunohistochemical markers of inflammation	Histology in SAT	0 minutes
Adipokine secretion of differentiating preadipocytes	Targeted adipokine analysis using immunoassay-based panels	0 minutes

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Lund University; Aarhus University Hospital
• Investigators: Principal Investigator: Charlotte Brøns, PhD, Steno Diabetes Center Copenhagen; Study Director: Allan Vaag, MD, PhD, Steno Diabetes Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: May 26, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; Liver fat; Metabolic disease; Adipose tissue biology
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Metabolic Diseases
• Other Study ID Numbers: NAFLD validation

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No