Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic model of critical illness.
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.
Heuer
Josef G
JG
Biotechnology Discovery Research Division, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. heuer_josef_g@lilly.com
Sharma
Ganesh R
GR
Zhang
Tonghai
T
Ding
Chunjin
C
Bailey
Dianna L
DL
Stephens
Eddie J
EJ
Holmes
Kimberly C
KC
Grubbs
Renee L
RL
Fynboe
Kelly A
KA
Chen
Yun-Fei
YF
Jakubowski
Joseph A
JA
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin