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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Non-Alcoholic Fatty Liver Disease, Low Birth Weight

Participation Criteria
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Eligibility Criteria
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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>30 kg/m2 Family history of diabetes (siblings, parent, and grandparents) 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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver fat, Non-alcoholic fatty liver disease, Metabolic disease, Adipose tissue biology