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NCT Number: NCT05890365

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

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.

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Key information

Age range

34 year–49 year

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Liver fat content

    Time frame: 0 minutes

    Liver elastography (FibroScan) and validation by MRS

Secondary outcomes

  1. Liver fibrosis

    Time frame: 0 minutes

    Liver elastography, validation by MR and liver histology

  2. Body composition

    Time frame: 0 minutes

    DEXA

  3. Fasting glucose

    Time frame: 0 minutes

    mmol/l

  4. Fasting insulin/C-peptide

    Time frame: 0 minutes

    pmol/l

  5. Fasting lipids

    Time frame: 0 minutes

    mmol/l

  6. Fasting liver enzymes

    Time frame: 0 minutes

    U/L

Other outcomes

  1. Transcriptomics in SAT and ex vivo cultured preadipocytes

    Time frame: 0 minutes

    RNAseq

  2. Epigenetics of SAT and ex vivo cultured preadipocytes

    Time frame: 0 minutes

    Genome-wide DNA methylation

  3. Functional characterization of lipid accumulation

    Time frame: 0 minutes

    Metabolism of ex vivo differentiated preadipocytes

  4. Functional characterization of lipolysis

    Time frame: 0 minutes

    Metabolism of ex vivo differentiated preadipocytes

  5. Functional characterization of glycolysis

    Time frame: 0 minutes

    Metabolism of ex vivo differentiated preadipocytes

  6. Functional characterization of respiration

    Time frame: 0 minutes

    Metabolism of ex vivo differentiated preadipocytes

  7. Adipocyte size

    Time frame: 0 minutes

    Histology in SAT

  8. Adipocyte collagen content

    Time frame: 0 minutes

    Histology in SAT

  9. Immunohistochemical markers of fibrosis

    Time frame: 0 minutes

    Histology in SAT

  10. Immunohistochemical markers of senescence

    Time frame: 0 minutes

    Histology in SAT

  11. Immunohistochemical markers of inflammation

    Time frame: 0 minutes

    Histology in SAT

  12. Adipokine secretion of differentiating preadipocytes

    Time frame: 0 minutes

    Targeted adipokine analysis using immunoassay-based panels

Study contacts

Contact information is provided by the study sponsor or research team.

Charlotte Brøns, PhD

CONTACT

[email protected]

+4526129093

Sponsors and collaborators

Lead sponsor

Steno Diabetes Center Copenhagen

Other

Collaborators

  • Aarhus University Hospital
  • Lund University

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Jun 6, 2023
Registry last updated
Jun 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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