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

Sponsor

Steno Diabetes Center Copenhagen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05890365

Collaborator

Aarhus University Hospital (Other), Lund University (Other)

300

Enrollment

17.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Low Birth Weight

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Outcome Measures

Primary Outcome Measures

Liver fat content [0 minutes]
Liver elastography (FibroScan) and validation by MRS

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 40 Years

Sexes Eligible for Study:

All

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)