Clinical trial NCT05890365: Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals
Official title: Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals - Extended Validation.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-Alcoholic Fatty Liver Disease
Low Birth Weight
Keywords: Metabolic disease
Adipose tissue biology
Liver fat
Non-alcoholic fatty liver disease
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Lund University
First posted: 2023-06-06
Enrollment: 300
Sex: ALL
Minimum age (years): 35
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy men and women aged between 35-40 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.

Brief summary: 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.

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), 35-40 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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver fat content
timeFrame: 0 minutes
Secondary outcomes:
measure: Liver fibrosis
timeFrame: 0 minutes
measure: Body composition
timeFrame: 0 minutes
measure: Fasting glucose
timeFrame: 0 minutes
measure: Fasting insulin/C-peptide
timeFrame: 0 minutes
measure: Fasting lipids
timeFrame: 0 minutes
measure: Fasting liver enzymes
timeFrame: 0 minutes
Other outcomes:
measure: Transcriptomics in SAT and ex vivo cultured preadipocytes
timeFrame: 0 minutes
measure: Epigenetics of SAT and ex vivo cultured preadipocytes
timeFrame: 0 minutes
measure: Functional characterization of lipid accumulation
timeFrame: 0 minutes
measure: Functional characterization of lipolysis
timeFrame: 0 minutes
measure: Functional characterization of glycolysis
timeFrame: 0 minutes
measure: Functional characterization of respiration
timeFrame: 0 minutes
measure: Adipocyte size
timeFrame: 0 minutes
measure: Adipocyte collagen content
timeFrame: 0 minutes
measure: Immunohistochemical markers of fibrosis
timeFrame: 0 minutes
measure: Immunohistochemical markers of senescence
timeFrame: 0 minutes
measure: Immunohistochemical markers of inflammation
timeFrame: 0 minutes
measure: Adipokine secretion of differentiating preadipocytes
timeFrame: 0 minutes
Locations:
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen
name: Allan Vaag, MD, PhD
role: STUDY_DIRECTOR
affiliation: Steno Diabetes Center Copenhagen
name: Charlotte Brøns, PhD
role: PRINCIPAL_INVESTIGATOR
References: