Preventive Potential of Bilirubin

Study Overview
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Brief Summary
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The prevalence of mild hyperbilirubinemia, also known as Gilbert´s Syndrome, is usually defined using an unconjugated bilirubin (UCB) blood concentration above 17.1 µmol/l. The prevalence of GS is remarkably common, affecting 5-10% (depending on ethnicity and gender) of the adult population. The aim of this project is to investigate whether there is a difference in health related marker between 60 subjects with Gilbert´s Syndrome (mild hyperbilirubinaemia) and 60 age and gender matched control subjects.

Official Title
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Investigating the Preventive Potential of Bilirubin

Conditions
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Mild Hyperbilirubinaemia

Intervention / Treatment
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* Other: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In general Signed declaration of consent Age: 20-80 years Liver enzymes (AST, ALT, GGT) < 1.5x over norm values Non smoking Moderate physical activity Ability to communicate with the study team in the local language to understand the study procedure Cases (GS): Total blood bilirubin > 1.2 mg/dl Unconjugated bilirubin > 1 mg/dl Controls (non-GS): Total blood bilirubin ≤ 1.2 mg/dl Unconjugated bilirubin ≤ 1 mg/dl Exclusion Criteria: In general Age < 20 or > 80 years Cardiovascular diseases Liver diseases (including Hep B and C) Cholelithiasis Hemolysis Renal diseases Active tumors Diabetes mellitus Smoking Professional athletes Subjects with organ transplants Intake of antioxidants within the last 4 weeks Intake of liver influencing medication within the last 5 weeks Cases (GS): Total blood bilirubin ≤ 1.2 mg/dl Unconjugated bilirubin ≤ 1 mg/dl Controls (non-GS): Total blood bilirubin > 1.2 mg/dl Unconjugated bilirubin > 1 mg/dl

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gilbert´s Syndrome<br>Subjects with mild hyperbilirubinaemia and a plasma level of unconjugated bilirubin of 17.1 µmol. | Other: No intervention<br>* No intervention. case - control design.<br>|
| Control group<br>Healthy controls with lower plasma level of unconjugated bilirubin of 17.1 µmol, aen and gender matched. | Other: No intervention<br>* No intervention. case - control design.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The investigators will consider Lipid parameter | Compare plasma parameter of lipid metabolism (Cholesterol, LDL, HDL, Triglycerides, ..) between Gilbert´s Syndrome subjects and controls. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The investigators will consider plasma parameter of glucose metabolism | Compare plasma parameter of glucose metabolism (plasma glucose (mg/dl), plasma insulin (µU/ml), C-peptide (ng/ml)) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider AMPK metabolic pathway | Compare parameter of the AMPK metabolic pathway (phosphorylated AMPK (rfU), phosphorylated Ppar-alpha (rfU), phosphorylated Ppar-gamma (rfU)) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider body composition | Compare parameter of the body composition (BMI (kg/m2), fat mass (%), waist circumference (cm), hip circumference (cm), abdominal circumference (cm)) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider heme catabolic pathway | Compare parameter of the heme catabolic pathway (expression of heme oxygenase (RQ), expression of Biliverdinreductase (RQ)) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider the metabolomic response | Compare the metabolomic pattern (ie all metabolites; analyzed using both nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider the composition of gut-microbiota | Compare the composition of the gut microbiota (Gene sequencing of the 16S rRNA on the stool samples are performed to identify the microbes down to genus level as well as the microbial diversity and relative abundance) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider oxidative stress marker | Compare plasma concentrations of oxidative stress marker such as malondialdehyde or GSH/GSSG between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider anabolic and catabolic hormones | Compare plasma concentrations of hormones (Glucagon (pg/ml), T3 (pg/ml), TSH(µM/ml),) between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider telomere length | Compare telomere length between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider RNA and DNA gene expression | Compare RNA and DNA gene expression between Gilbert´s Syndrome subjects and controls. | Baseline | 
| The investigators will consider the metabolomic response after a standard breakfast | Compare the metabolomic pattern after a standard breakfast (ie all metabolites; analyzed using both nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques) between Gilbert´s Syndrome subjects and controls. | Five blood samplings over 180 minutes. |