Glucose and surgical sepsis: a study of underlying immunologic mechanisms.
BACKGROUND
Early clinical trials investigating the role of tightly controlled glucose levels showed marked benefit in survival of critically ill patients. However, a recent meta-analysis and large randomized controlled trial have failed to reproduce the benefit, showing instead substantially increased risk of dangerous hypoglycemia. We sought to investigate the effects of varying glucose concentrations on previously tested, prognostically significant, innate immune parameters, to define any potential effects of glucose at the cellular level.


METHODS
After formal approval and informed consent, venous blood samples were collected from young healthy volunteers. Up to 11 corresponding (same-subject) samples were incubated at 100, 350, or 600 mg/dL glucose concentrations and analyzed to determine human leukocyte antigen-DR surface receptor expression, cytokine release, phagocytic capacity, and formation of reactive oxygen species. Data are presented as mean +/- SEM.


RESULTS
After incubation, the change in human leukocyte antigen-DR mean channel fluorescence from resting baseline values in lipopolysaccharide-stimulated monocytes was not significantly different between 100, 350, and 600 mg/dL (1,749 +/- 110; 1,748 +/- 120; and 1,725 +/- 96, respectively; p = 0.89). Tumor necrosis factor-alpha concentrations were significantly lower for samples incubated at higher glucose concentrations (179 +/- 50 pg/mL, 125 +/- 30 pg/mL, and 107 +/- 29 pg/mL; p < 0.05). The phagocytic capacity of the innate immune system was marginally enhanced by glucose. However, the formation of reactive oxygen species was markedly impaired by rising glucose (55% to 66% impairment; p < 0.05).


CONCLUSIONS
Increasing glucose concentrations exert considerable opposing effects on several well-established innate immunologic processes. The opposing findings might contribute to recent clinical controversies. Physician judgment and experience are essential to imminent treatment of critically ill and perioperative surgical patients.
The Price Institute of Surgical Research, University of Louisville School of Medicine, 511 S. Floyd Street, Louisville, KY 40202, USA. m0qada01@louisville.edu
Motaz
M
Qadan
E Brooks
EB
Weller
Sarah A
SA
Gardner
Claudio
C
Maldonado
Donald E
DE
Fry
Hiram C
HC
Polk
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis*; D016638:Critical Illness; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000276:immunology; D007111:Immunity, Cellular; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000097:blood; D018805:Sepsis / Q000097:blood / Q000276:immunology*; D013514:Surgical Procedures, Operative
D001786:Blood Glucose; D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D017382:Reactive Oxygen Species