Insulin therapy for hyperglycemia in neonatal sepsis using a preterm mouse model. Issue 5 (28th May 2020)

• Record Type: Journal Article
• Authors: Miyauchi, Harunori; Fujioka, Kazumichi; Okubo, Saki; Nishida, Kosuke; Ashina, Mariko; Ikuta, Toshihiko; Okata, Yuichi; Maeda, Kosaku; Iijima, Kazumoto; Bitoh, Yuko
• Is Part Of: Pediatrics international. Volume 62:Issue 5(2020)
• Page Start: 581
• Page End: 586
• Publication Date: 2020-05-28
• Subjects: hyperglycemia -- insulin therapy -- mouse model -- neonatal peritoneal sepsis; Pediatrics -- Periodicals; 618.92
• DOI: 10.1111/ped.14126
• Languages: English
• ISSNs: 1328-8067

Abstract

Abstract: Background: 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. Methods: A stock cecal slurry (CS) solution was prepared from adult cecums and 3.0 mg 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 9 h 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. Results: Blood glucose levels were significantly higher than those of baseline levels with a peak at 3 h, which progressively decreased from 6 to 9 h post‐sepsis induction. Insulin treatment reduced post‐sepsis‐induced hyperglycemia at 1.5 and 3 h. 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. Conclusions: 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.