A New Model of Acute Febrile Disease

Not Applicable

Completed

Brief Summary: The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation/fever and then fast and bedrest for 36 hours. Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.

Detailed Description: The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation on study day 1 and then fast and bedrest for 36 hours (Study day 2). Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Participation in trials using ionized radiation a year prior to this trial.
Comprehensive x-ray examinations in the study period.
In case of immobilization of an extremity, the extremity should be fully re- habilitated and this should be stated by a physician or physiotherapist. The test subject's word for this will be sufficient.
Allergies to eggs or soy oil.
Diseases: Diabetes, epilepsy, ongoing infectious disease, immunodeficiency, heart disease, dysregulated hypertension.

Arm && Interventions

Group	Intervention	Description
"LPS, 36 hour immobilization and fast"	LPS, 36 hour immobilization and fast	Interventions: Test subjects undergo 48 hour exercise restriction and overnight fast. Study day 1: - LPS (1 ng/kg) will be administered. Test subjects will fast and bedrest for the rest of the study period. Study day 2: * 3 hour Basal period: Continued fast and bedrest. Phenylalanine, tyrosine, carbamide, glucose and palmitate tracers are infused. Muscle and fat biopsies are taken from m. vastus lateralis and stomach. * 3 hour hyperinsulinemic euglycemic clamp period with muscle and fat biopsies. Study day 3: - Blood sample.

Primary Outcome Measures

Name	Time	Method
insulin sensitivity	After a 3 hour clamp	Measured by hyperinsulinemic euglycemic clamp technique

Secondary Outcome Measures

Name	Time	Method
Energy expenditure	measured at baseline and after 3 hours of clamp for 15 minutes	measured by indirect calorimetry
Protein metabolism	measured at baseline and after 3 hours of clamp	Quantified by phenylalanine and tyrosine tracer methodology (whole body and the forearm model)
ketone body metabolic changes	measured at baseline and after 3 hours of clamp	measurement of ketone bodies
inflammation	measurements over 36 hours	Quantified by C-reactive peptide (CRP), white blood cell count, cytokines
Intracellular signalling pathway activation	measured at baseline and after 3 hours of clamp	Intracellular signalling pathway activation in muscle and fat
Hormonal changes	measured at baseline and after 3 hours of clamp	measures of insulin, glucagon, c-peptide and growth hormone
CD163	0, 24 and 48 hours after LPS exposure	measures of CD163 and soluble CD163 (sCD163) after LPS exposure
Glucose metabolism	measured at baseline and after 3 hours of clamp	measured by glucose tracer, calculations of rate of appearance, disappearance and endogenous glucose production
Urea balance	measured at baseline and after 3 hours of clamp	measured by urea tracer and urine nitrogen excretion.
Glucose uptake by the forearm	measured at baseline and after 3 hours of clamp	Arterio-venous balance x blodflow
Fat metabolism	measured at baseline and after 3 hours of clamp	measured by palmitate tracer, calculating whole body palmitate flux. Measures of free fatty acids.