Short-term hyperglycemia in surgical patients and a study of related cellular mechanisms

Abstract

Objective: To examine cellular mechanisms by which short-term elevations of glucose or insulin impair leukocyte functions and to assess the occurrence of perioperative hyperglycemia in surgical patients.

Summary background data: A major factor in the contemporary management of the critically ill surgical patient is the progressively exact control of blood glucose. However, the separate role of insulin and underlying immunologic mechanisms are not well understood.

Methods: Venous blood samples of 20 healthy volunteers were exposed for 24 hours to various glucose and insulin concentrations. Lipopolysaccharide (LPS) was added at 1 ng/mL for up to 16 hours and the monocytes' ability to express CD14 and HLA-DR assessed as an index of the monocyte's capability to present antigen. To evaluate the clinical importance of the observed experimental results, a prospective evaluation of perioperative blood glucose values in 5285 surgical patients in Kentucky was performed.

Results: Both exposure to high glucose (400 mg/dL) and insulin (100 muU/mL) led to an independent and additive impairment of monocyte HLA-DR expression after 24 hours (P < 0.01). Perioperative blood glucose exceeded 200 mg/dL in 21% of all cardiothoracic patients and in 31% of diabetic patients undergoing common major operations.

Conclusions: Both short-term hyperglycemia and hyperinsulinemia are associated with significantly decreased monocyte HLA-DR expression, a parameter correlating with infectious complications and patient mortality. This may provide a mechanism by which high glucose and insulin impair innate immunity. It also appears that perioperative maintenance of normoglycemia will become a valid performance measure for practicing surgical specialists.

FIGURE 1. Monocyte HLA-DR expression as a function of increasing lengths of LPS stimulation at different glucose and insulin concentrations (n = 20). *All P < 0.05 (400 mg/dL vs. 100 mg/dL glucose). ‡All P < 0.01 (400 mg/dL glucose + 100 μU/mL insulin vs. 100 mg/dL glucose without insulin).

FIGURE 2. A, Monocyte HLA-DR expression after 24 hours of incubation at 100 mg/dL versus 400 mg/dL glucose and 400 mg/dL glucose with high insulin (100 μU/mL). 2 hours LPS, n = 12. *P = 0.005 (400 mg/dL vs. 100 mg/dL glucose). ‡P = 0.002 (400 mg/dL glucose + 100 μU/mL insulin vs. 100 mg/dL glucose). B, Control experiments for increased osmolarity: Monocyte HLA-DR expression in the presence of 8.25 mm/L (≈16.5 mOsm/L) NaCl and 100 mg/dL (5.5 mmol/L) glucose (≈5.5 mOsm) as compared with normoglycemic control samples (*P = 0.74). n = 20.

FIGURE 3. A, Comparison of monocyte HLA-DR expression at normal (10 μU/mL) versus high (100 μU/mL) insulin concentrations after 24 hours of incubation and different lengths of LPS (1 ng/mL). n = 20. B, Effect of increasing concentrations of insulin on monocyte HLA-DR expression in a hyperglycemic (400 mg/dL glucose) environment (*P < 0.05). n = 12.