Insulin-like Growth Factor I and its binding protein 3 in sepsis

Abstract Objective To investigate the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-I) axis and identify the factors that determine IGF-I levels in adult septic patients of variable severity, i.e., with sepsis, severe sepsis or septic shock, in the acute phase of disease. Design In 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50 with septic shock), GH, IGF-I, Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), insulin, cortisol, albumin, thyroid hormones, C-reactive protein and interleukin-6 serum levels were measured once within 48 h after onset of a septic episode. Twenty-nine healthy volunteers served as controls. Results IGF-I and IGFBP-3 levels were decreased in patients with sepsis and severe sepsis (versus controls), decreasing further in patients with septic shock (versus sepsis). IGF-I levels were positively related to IGFBP-3, albumin, triiodothyronine and thyroxine, and inversely related to cortisol, sepsis severity, C-reactive protein, interleukin-6 and age. In multiple regression analysis, IGF-I levels were independently related to IGFBP-3 and albumin (lower in patients with decreased IGFBP-3 and albumin levels) (p < 0.001 and p = 0.01, respectively), and cortisol (lower in patients with increased cortisol levels) (p = 0.04). IGFBP-3 accounted for most of the variance explained by the model (R2 = 0.519). GH levels were not related to IGF-I levels or mortality. IGF-I and IGFBP-3 levels were not associated with mortality. Conclusions The GH/IGF-I axis is severely disrupted in septic patients. IGFBP-3 is the major determinant of IGF-I levels.