A model mimicking catabolic inflammatory disease; a controlled randomized study in humans

Inflammatory disease is catabolic and associated with insulin resistance, increased energy expenditure, lipolysis and muscle protein loss. The main contributors to these metabolic adaptations are inflammation, malnutrition and immobilisation. Controlled experimental models incorporating these central elements of hospitalisation are lacking. The aim of this study was to validate such a human experimental model. In a randomized crossover design, six healthy young men underwent; (i) overnight fast (CTR), or (ii) exposure to systemic lipopolysaccharide (1 ng/kg) combined with 36-hour fast and bed rest (CAT). The difference in insulin sensitivity between CAT and CTR was the main outcome, determined by a hyperinsulinemic euglycemic glucose clamp. Palmitate, glucose, urea, phenylalanine and tyrosine tracers were infused to estimate metabolic shifts during interventions. Indirect calorimetry was used to estimate energy expenditure and substrate oxidation. Insulin sensitivity was 41% lower in CAT than in CTR (M-value, mg/kg/min): 4.3 ± 0.2 vs 7.3 ± 1.3, p