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| Name | Class |
|---|---|
| Aarhus University Hospital | OTHER |
| Lund University | OTHER |
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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.
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.
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| Measure | Description | Time Frame |
|---|---|---|
| Liver fat content | Liver elastography (FibroScan) and validation by MRS | 0 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Liver fibrosis | Liver elastography, validation by MR and liver histology | 0 minutes |
| Body composition | DEXA | 0 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Transcriptomics in SAT and ex vivo cultured preadipocytes | RNAseq | 0 minutes |
| Epigenetics of SAT and ex vivo cultured preadipocytes | Genome-wide DNA methylation |
Inclusion Criteria:
Exclusion Criteria:
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Healthy men and women aged between 34-49 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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Charlotte Brøns, PhD | Contact | +4526129093 | charlotte.broens.01@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Allan Vaag, MD, PhD | Steno Diabetes Center Copenhagen | Study Director |
| Charlotte Brøns, PhD | Steno Diabetes Center Copenhagen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Steno Diabetes Center Copenhagen | Recruiting | Herlev | 2730 | Denmark |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D008659 | Metabolic Diseases |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Abdominal subcutaneous adipose tissue biopsies are retained
| 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 |
| 0 minutes |
| Functional characterization of lipid accumulation | Metabolism of ex vivo differentiated preadipocytes | 0 minutes |
| Functional characterization of lipolysis | Metabolism of ex vivo differentiated preadipocytes | 0 minutes |
| Functional characterization of glycolysis | Metabolism of ex vivo differentiated preadipocytes | 0 minutes |
| Functional characterization of respiration | Metabolism of ex vivo differentiated preadipocytes | 0 minutes |
| Adipocyte size | Histology in SAT | 0 minutes |
| Adipocyte collagen content | Histology in SAT | 0 minutes |
| Immunohistochemical markers of fibrosis | Histology in SAT | 0 minutes |
| Immunohistochemical markers of senescence | Histology in SAT | 0 minutes |
| Immunohistochemical markers of inflammation | Histology in SAT | 0 minutes |
| Adipokine secretion of differentiating preadipocytes | Targeted adipokine analysis using immunoassay-based panels | 0 minutes |