Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations

Abstract

Aim: In human sepsis, a prominent component of the hypermetabolite is impaired glucose tolerance (IGT) and hyperglycemia. Elevations in plasma glucose concentration impair immune function by altering cytokine production from macrophages. We assessed the role of glucose in the regulation of circulating levels of insulin, glucagon, cortisol, IL-6 and TNF-alpha in human sepsis with normal or impaired glucose tolerance.

Methods: According to the results of intravenous glucose tolerance test, forty patients were classified into two groups: control group (n=20) and IGT group (n=20). Plasma glucose levels were acutely raised in two groups and maintained at 15 mmol/L for 3 hours. Plasma insulin, glucagon and cortisol levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA.

Results: In IGT group, the fasting concentrations of plasma glucose, insulin, glucagon, cortisol, IL-6 and TNF-alpha levels were significantly higher than those in control group (P<0.05). During clamp, the control group had a higher average amount of dextrose infusion than the IGT group (P<0.01). In control group, plasma insulin levels rose from a basal value to a peak at an hour (P<0.05) and maintained at high levels. Plasma glucagon levels descended from a basal value to the lowest level within an hour (P<0.01) and low levels were maintained throughout the clamp. In IGT group, plasma insulin was more significantly elevated (P<0.01), and plasma glucagon levels were not significantly declined. Plasma cortisol levels were not significantly changed in two groups. In control group, plasma IL-6 and TNF-alpha levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In IGT group, increased levels of plasma cytokine lasted longer than in control group (3 hours vs 2 hours, P<0.05), and the cytokine peaks of IGT group were higher (P<0.05) than those of control group.

Conclusion: Acute hyperglycemia pricks up hyperinsulinemia and increases circulating cytokine concentrations and these effects are more pronounced in sepsis with IGT. This suggests a potential modulation of immunoinflammatory responses in human sepsis by hyperglycemia.

Figure 1

Circulation insulin levels during hyperglycemia clamps in 20 patients of control group (○-○) and in 20 pa-tients of IGT group (△-△). Mean ± S.E.M. in human sepsis. Plasma insulin levels rose from a basal value to a peak within an hour (P < 0.01) and high levels maintained in two groups.

Figure 2

Circulation glucagon levels during hyperglycemia clamps in 20 patients of control group (○-○) and in 20 pa-tients of IGT group (△-△). Mean ± S.E.M. in human sepsis. In control group, plasma glucagon levels decreased from a basal value to the lowest level within half an hour (P < 0.01) and a low level maintained, and was not significantly declined in IGT group in the entire observation period.

Figure 3

Circulation cortisol levels during hyperglycemia clamps in 20 patients of control group (○-○) and in 20 pa-tients of IGT group (△-△). Mean ± S.E.M. in human sepsis. There were no significant changes in two groups.

Figure 4

Circulation IL-6, TNF-α levels during hyperglyce-mia clamps in 20 patients of control group (○-○) and in 20 patients of IGT group (△-△). Mean ± S.E.M. in human sepsis. In two groups, plasma IL-6, TNF-α levels rose from a basal value to a peak within 1 hour (P < 0.01). In IGT group, increased level of plasma TNF-α, IL-6 during the clamping lasted longer than in control group (3 hours vs. 2 hours; P < 0.05).