Abstract:

Objective To investigate the correlation of stress hyperglycemia with serum levels of C reactive protein(CRP), interleukin-6(IL-6) and macrophage migration inhibiting factor(MIF) that reflect the inflammatory status and with the expression of human leucocyte antigen DR(HLA-DR) on peripheral monocytes in critically illed patients with trauma or infection; and to investigate the effect of intensive insulin therapy and glycemic control on inflammatory response and immune function in critical illness.Methods Thirty-three critically illed patients were randomly divided into the control group(maintenance blood glucose at a level between 9.99 and 11.10 mmol/L), glycemia controlling group 1(maintenance blood glucose at a level between 4.44 and 6.11 mmol/L), and glycemia controlling group 2(maintenance blood glucose at a level between 6.66 and 8.33 mmol/L). Critically illed patients with APACHEⅡscore≥10 after trauma or infection were enrolled. Patients with insulin-dependent diabetes mellitus, immune disease or history of long-term immunoregulating medicine taking were excluded; patients less than 18 years old were also excluded. Target glycemia was obtained by insulin infusion. The glycemia level was determined every one to two hours. The interval of glycemic measurement might prolong when target glycemia was achieved. The expression of human leucocyte antigen DR on peripheral monocytes was measured in all 33 patients with flow cytometry on 1, 4 and 7 of intensive care in parallel with C reactive protein. In the meantime, Enzyme-linked immunoadsorbent assay(ELISA) was used to determine the interleukin-6 and macrophage migration inhibiting factor. The same nutritional support was applied to all patients. Data were expressed as Mean±SD and analyzed by using Analysis of Variance and correlation and linear regression. A p value <0.05 was regarded as statistically significant in all the tests conducted in this study.Results 1) The incidence of stress hyperglycemia was very high, being 97% in this study. There was no hypoglycemia happened in these patients. 2) Compared with the control group and glycemia controlling group 2, glycemia controlling group 1 needed more insulin to achieve target glycemia. 3) There were much increase in serum levels of C reactive protein, interleukin-6 and macrophage migration inhibiting factor and decrease in the expression of human leucocyte antigen DR on peripheral monocytes in all 33 critically illed patients with trauma or infection. C reactive protein was positively correlated with the level of blood glucose, human leucocyte antigen DR was negatively correlated with the level of blood glucose. 4) The levels of C reactive protein, interleukin-6 and macrophage migration inhibiting factor decreased while the expression of human leucocyte antigen DR on peripheral monocytes gradually recovered with the patients improving. 5) Compared with the control group and glycemia controlling group 2, the human leucocyte antigen DR expression of peripheral monocytes in glycemia controlling group 1 increased. There were significant difference on 4 and 7 after admission in Surgical Intensive Care Unit(P<0.05). C reactive protein and interleukin-6 were much decreased on 7 d after intensive insulin therapy(P<0.05); macrophage migration inhibiting factor was also decreased, but the deference was not significant statistically(P>0.05).Conclusion 1) Serum inflammatory factors are much increased in critically ill patients with trauma or infection. Their immune functions are affected. Stress hyperglycemia happens at the same time. Some inflammatory factors are positively correlated with the level of blood glucose. Immune functions are negatively correlatied with the level of blood glucose. Inflammatory factors gradually decrease and immune functions recover with weakening of stress. 2) Tight glucose control with intensive insulin therapy can increase the human leucocyte antigen DR expression of peripheral monocytes. It also can attenuate the systemic inflammatory response in critically illed patients. 3) Control of glycemia to the normal range may have anti-inflammatory and immunoregulatory effect.

Key words: tight glucose control, intensive insulin therapy, stress induced hyperglycemia