Overview

This trial is active, not recruiting.

Condition healthy adults with normal bmi
Treatment fat/inflammation effects
Phase phase 4
Sponsor German Diabetes Center
Start date March 2009
End date September 2011
Trial size 16 participants
Trial identifier NCT01054989, FIRE-01

Summary

The combination of impaired insulin sensitivity and insulin secretion is thought to be the basis of type 2 diabetes. Increased free fatty acids levels impair insulin action in muscle and liver, but also systemic inflammation processes play a role in the development of insulin resistance.

This study compares the effects of fat and inflammation on insulin sensitivity, systemic inflammation, energy metabolism, vascular system and neural function in healthy humans.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking open label
Primary purpose basic science
Arm
(Active Comparator)
Intravenous application of fat
fat/inflammation effects
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
(Active Comparator)
Oral fat load
fat/inflammation effects
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
(Active Comparator)
Lipopolysaccharide (LPS; US Standard Reference endotoxin)
fat/inflammation effects
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours
(Placebo Comparator)
Intrevenous glycerol infusion
fat/inflammation effects
Fat infusion (Intralipid) over 6 hours Fat orally (Soy bean oil) single dose LPS infusion for 10 minutes Glycerol infusion over 6 hours

Primary Outcomes

Measure
Effect of intervention on whole body insulin sensitivity
time frame: 6 hours

Secondary Outcomes

Measure
Effect of intervention on systemic inflammation
time frame: 1-6 hours
Effect of intervention on cellular immune mechanisms
time frame: 6 hours

Eligibility Criteria

Male or female participants from 20 years up to 40 years old.

Inclusion Criteria: - Healthy male and female subjects - Age 20-40 - BMI 20-25 mg/m2 Exclusion Criteria: - Hyperlipidemia - Smoking - Pregnancy - Acute infection - Anaemia - Taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive medication - Malignancies - Any chronic disease - Autoimmune or immune compromising diseases including HIV/AIDS - Allergies against study drugs - Hepatitis - Gall bladder diseases - Renal failure - Psychiatric diseases or addiction

Additional Information

Official title Fat, Inflammation and Insulin Resistance (FIRE-Study)
Principal investigator Bettina Nowotny, MD
Description A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) is known represent one key mechanism in the pathophysiology of insulin resistance, which is subsequently known to be the basis of the development of type 2 diabetes. But also inflammatory processes, also known as subclinical inflammation, have been shown to be independently associated with insulin resistance and diabetes development. The aim of this study is to analyse the causal relationship between FFA and inflammation in the induction of insulin resistance in healthy humans. It is known that the parenteral application of lipids over 4-6 hours results in an increase of FFA and a subsequent induction of a transient insulin resistance in peripheral tissues. Whether oral fat intake has similar effect is still unknown. On the other hand the oral intake of a high fat meal acutely increases intestinal permeability and thereby the levels of bacterial lipopolysaccharide (LPS) in the bloodstream. LPS is known to be a potent stimulator of immune response on a subclinical level accompanied by elevated levels of immune mediators, which in turn impair the insulin receptor signalling pathway leading to insulin resistance. Thus, in this study the effects of fat, both by an oral or parenteral fat load, and by a short-term LPS-infusion simulating the postprandial systemic LPS peak compared to a control infusion (glycerol) on insulin resistance is analysed. Insulin resistance and hepatic glucose production is determined by an hyperinsulinemic euglycemic clamp including glucose tracers. To detect the effects on the immune system on different levels, we measure 1) circulating levels of immune mediators by ELISA and bead-based mulitiplex assays, 2) gene expression of leukocytes, 3) subfractions of circulating leukocytes by FACS and 4) the stimulatory capacity of isolated lymphocytes and monocytes in vitro. Moreover, the effects of fat or inflammation on the function of the autonomic nervous system and the vasculature are studied. A second focus is the impact of the interventions on signal transduction and mitochondrial function in muscle and as well as on the metabolism and inflammation in subcutaneous adipose tissue in muscle and fat biopsies.
Trial information was received from ClinicalTrials.gov and was last updated in July 2012.
Information provided to ClinicalTrials.gov by German Diabetes Center.