title: Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic model of critical illness.
abstract: BACKGROUND
  The effects of hyperglycemia and insulin therapy on septic outcome have not been well studied.
  
  
  METHODS
  Septic hyperglycemia was induced by infusion of TPN (254 kcal/kg x d) immediately following cecal ligation and puncture (CLP) surgery in rats. Animals (N = 109) were monitored for blood glucose and followed for survival for 4 days. Separate cohorts (N = 36) were sacrificed at 22 hours post-CLP and analyzed for cytokines/chemokines, hormones, and organ damage markers. The effects of insulin treatment on 4 day survival were also examined (N = 60).
  
  
  RESULTS
  Hyperglycemic septic animals had significantly higher blood glucose (p < 0.0001), plasma proinflammatory cytokine levels, serum organ damage markers (p < 0.05) and reduced mean survival time (p < 0.001). Insulin treatment (2 IU/kg/hr) resulted in significantly lower blood glucose (p < 0.01) and improved 4 day survival (p < 0.03).
  
  
  CONCLUSIONS
  Hyperglycemia is associated with greater morbidity and mortality in sepsis. Insulin therapy significantly improved survival suggesting that management of hyperglycemia with insulin may improve outcome in septic patients.
authors.affiliation: Biotechnology Discovery Research Division, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. heuer_josef_g@lilly.com
authors.forename: Josef G
authors.initials: JG
authors.lastname: Heuer
authors.forename: Ganesh R
authors.initials: GR
authors.lastname: Sharma
authors.forename: Tonghai
authors.initials: T
authors.lastname: Zhang
authors.forename: Chunjin
authors.initials: C
authors.lastname: Ding
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Bailey
authors.forename: Eddie J
authors.initials: EJ
authors.lastname: Stephens
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Holmes
authors.forename: Renee L
authors.initials: RL
authors.lastname: Grubbs
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Fynboe
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004195:Disease Models, Animal; D005260:Female; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin