Jun 20, 2012

A human model of inflammatory cardio-metabolic dysfunction; a double blind placebo-controlled crossover trial

Journal of Translational Medicine
Nehal N MehtaMuredach P Reilly

Abstract

Chronic inflammation may contribute to insulin resistance (IR), metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8) were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg). We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT) was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to underst...Continue Reading

  • References38
  • Citations20

References

  • References38
  • Citations20

Citations

Mentioned in this Paper

Metabolic Process, Cellular
Neuro-Oncological Ventral Antigen 2
Real-Time Polymerase Chain Reaction
Insulin Sensitivity
Endotoxemia
Tumor Necrosis Factor-alpha
C-reactive Protein Measurement
Whole Blood
Systemic Inflammatory Response Syndrome
Genome

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