DISTURBED ANABOLIC HORMONAL PATTERNS IN BURNED PATIENTS - THE RELATION TO GLUCAGON

OBJECTIVE Complex changes in the anabolic regulators of metabolism occ ur after major injury. We have studied the time course for IGF-I and I GFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during th e onset of sepsis were also investigated. PATIENTS Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42(6)%) w ere studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven of the eight patients dev eloped sepsis, confirmed with positive blood cultures, during the stud y period. Six of the eight survived. MEASUREMENTS The hormonal changes determined in the morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsi s were studied by normalizing all data to the day of positive blood cu ltures and clinical onset of sepsis. RESULTS On admission, plasma leve ls of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I wer e low. During the first week after the burn, morning levels of glucago n and insulin increased while levels of GH and IGF-I decreased. GH lev els were still elevated compared to healthy subjects. Despite the incr ease in insulin levels, IGFBP-1 remained elevated. Three weeks after t he burn injury, IGF-I levels were increased but still markedly below n ormal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Ad mission levels of IGFBP-1 correlated to nitrogen loss (negative nitrog en balance) during the first 24 hours after the burn (r=0.84, P<0.05). A correlation between negative nitrogen balance and glucagon levels w as found during the early catabolic period in the rehydration period ( i.e. days 2-3, r=0.84, P<0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (da ys 2-3 vs admission, r=0.85, P<0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration per iod (days 2-3, r=0.77, P<0.05) and the third week after the burn (r=0. 77, P<0.05). During the most catabolic phase in the first week after t he burn (TPN period) there was an inverse relation between IGF-I and I GFBP-1 levels (r=-0.83, P<0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glu cagon (r=-0.83, P<0.05). Sepsis, superimposed upon the burn trauma, wa s associated with transient elevations in IGFBP-1 and reductions in in sulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. CONCLUSIONS The present findings show that marked ch anges in important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the in hibitory effects of insulin on IGFBP-1, both contribute to the reducti on in IGF-I levels and bioavailability, factors which may play an impo rtant role in post injury metabolism. Furthermore, these data suggest that of the catabolic hormones (catecholamines, cortisol and glucagon) , primarily glucagon seem to be involved in the modulation of IGF-I an d IGFBP-1 levels following burn injury.