Insulin therapy for hyperglycemia in neonatal sepsis using a preterm mouse model.

Abstract

Stress-induced hyperglycemia is a frequent complication of neonatal sepsis. Hyperglycemia induces oxidative stress and immunosuppression. We investigated the glucose kinetics and effect of insulin administration during stress-induced hyperglycemia in a neonatal sepsis mouse model. A stock cecal slurry (CS) solution was prepared from adult cecums and 3.0mg of CS/g (LD40 ) was administered intraperitoneally to 4-day-old FVB mouse pups. Blood glucose levels were measured at 1.5, 3, 6, and 9h post-sepsis induction and compared with basal levels. Two different doses of ultrafast-acting insulin were administered subcutaneously, and blood glucose levels and survival rates were monitored. Blood glucose levels were significantly higher than those of baseline levels with a peak at 3h, which progressively decreased from 6 to 9h post-sepsis induction. Insulin treatment reduced post-sepsis-induced hyperglycemia at 1.5 and 3h. The mortality rate of CS-only pups (39%) was similar to that of CS+1 U/kg insulin pups (60%). However, the mortality rate of CS+5 U/kg insulin pups (82%) was significantly higher than that of CS-only pups. Marked hyperglycemia was induced immediately after post-sepsis induction, and the high-dose insulin treatment increased mortality post-induction. Stress-induced hyperglycemia could therefore be a physiological and protective response for preterm sepsis, and aggressive treatment of this hyperglycemia might be contraindicated.