Decreased serum insulin-like growth factor-I in burn patients: relationship with serum insulin-like growth factor binding protein-3 proteolysis and the influence of lipid composition in nutritional support.

OBJECTIVES

To test the effects of the amount and type of fat in the nutritional support on serum insulin-like growth factor (IGF)-I concentrations in burn patients and to test the hypothesis that the serum proteolytic activity for insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the decreased serum IGF-I observed in these patients.

DESIGN

Randomized, double-blind trial of three different nutritional supports and analysis of serum IGF-I, IGFBP-3, and serum IGFBP-3 proteolysis.

SETTING

Burn center in a university hospital.

PATIENTS

A total of 23 severely burned (>25% total body surface area burned) adult patients.

INTERVENTIONS

Patients were randomly assigned to three types of nutritional support differing in the amount of energy derived from fat and the presence or absence of fish oil: Group I (control), 35% fat; Group II, 15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both parenteral and enteral and was started within 24 hrs of admission.

MEASUREMENTS AND MAIN RESULTS

Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every 3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3 was measured as well. Serum IGF-I concentration was low in all subjects throughout the study period, but did increase with time (p < .01); significantly higher values were found in Group III (p < .05). Multivariate analysis showed that fish oil and low fat solutions were significantly correlated to serum IGF-I concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal throughout the study with no difference between the groups. Between days 4 and 16, IGFBP-3 was cleaved into two fragments in all patients studied, and the molecular weights of the fragments were equal to those observed in the serum of a woman late in pregnancy. During this period of time, serum proteolytic activity for rhIGFBP-3 was >30% in 24 of the 30 samples measured, whereas 20 of the 28 samples measured thereafter were normal (<25%). Serum IGFBP-3 concentration from ligand binding assay was correlated with serum proteolytic capacity in all subjects (mean r2 = 0.77; p < .01) and with serum IGF-I concentrations in five of six subjects (mean r2 = 0.81; p < .01).

CONCLUSIONS

In burn injury, serum IGF-I concentrations are sensitive to the amount and type of fat in their nutritional support. The presence of fish oil allowed for a more rapid recovery of serum IGF-I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased serum IGF-I values and the protease(s) responsible for this seem to be similar to those observed in late pregnancy.