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| Name | Class |
|---|---|
| Danish Diabetes Academy | OTHER |
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Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiac steatosis. The mechanisms behind why some subjects progress from NAFLD to NASH and the link between cardiac involvement and NAFLD are poorly understood, but must include altered cardiac and intrahepatic lipid handling. Investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with type 2 diabetes with and without NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in type 2 diabetic subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using tracer techniques (11Cpalmitate PET tracers and triglyceride (TG) tracers) to study cardiac and liver substrate trafficking, as well as MR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Type 2 Diabetes with NAFLD | Active Comparator | Patients with Type 2 Diabetes with NAFLD MR spectroscopy verified no steatosis |
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| Type 2 Diabetes without NAFLD | Active Comparator | Patients with Type 2 Diabetes without NAFLD MR spectroscopy verified steatosis |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperinsulinemic euglycaemic clamp | Other | Infusion of constant intravenous insulin to achieve hyperinsulinemia and concomitant infusion of glucose to maintain euglycemia (plasma glucose at 5 mM). Infusion of palmitate and VLDL-triglyceride tracer. PET/CT scans of heart and liver, both in basal period and during intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Fatty acid uptake in Heart (mg/kg/min) | Infusion of [11-C] palmitate and measured by PET/CT scan. | 1 day |
| Fatty acid oxidation in Heart (µmol/min) | Infusion of [11-C] palmitate and measured by PET/CT scan. | 1 day |
| Measure | Description | Time Frame |
|---|---|---|
| VLDL-triglyceride secretion (µmol/min) | Ex vivo labeled VLDL [14C]-triolein tracer technique. | 1 day |
| VLDL-triglyceride oxidation (µmol/min) | Oxidation is measured by specific activity in exhaled air. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Endocrinology and Internal Medicine | Aarhus N | 8200 | Denmark |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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|
| 1 day |
| Fatty acid uptake in liver (mg/kg/min) | Infusion of [11-C] palmitate and measured by PET/CT scan. | 1 day |
| Fatty acid oxidation in liver (µmol/min) | Infusion of [11-C] palmitate and measured by PET/CT scan. | 1 day |
| VLDL-triglyceride uptake in muscle (percent) | Measurement of fatty acid concentration and specific activity in muscle biopsies | 1 day |
| VLDL-triglyceride uptake in adipose tissue (percent) | Measurement of fatty acid concentration and specific activity in adipose tissue biopsies | 1 day |
| D004700 | Endocrine System Diseases |