应激性高糖血症与胰岛素抵抗的相关因素研究

目的探讨危重病应激状态与高糖血症相关的发病环节及致病因素。方法采用放射免疫分析或双抗体夹心酶联免疫吸附法测定47例应激性高糖血症(SHG)危重患者和15名正常人的血糖(BG)、胰岛素(INS)、C-肽(C-P)、胰高血糖素(Gluc)、生长激素释放抑制因子(SS)、皮质醇(Cor)、肿瘤坏死因子-α(TNF-α)、人可溶性TNF受体(sTNFR)和sTNFR,并计算胰岛素敏感指数(ISI)。结果147例SHG患者中存活36例,死亡11例;入重症监护室(ICU)24h内的急性生理学与慢性健康状况评分系统(A-PACHE)为(13.89±6.29)分,住ICU时间为(5.5±6.3)d,机械通气(MV)时间为(51.49±66.01)h。2SHG组的各项检测结果均明显高于正常对照组,除SS外,余各指标差异均有显著性(P<0.05或P<0.01)。3随着BG增高,反映胰腺β细胞功能的C-P浓度增高,ISI越差。4对不同APACHE评分分组比较显示,BG并不随病情危重程度的增加而升高,但MV时间、Cor、Gluc、SS、TNF-α、sTNFR和sTNFR均随病情的危重程度而增加,差异均有显著性。5SHG对MV时间的影响差异有显著性(F=10.438,P<0.01),而对年龄、预后、住ICU时间的影响差异均无显著性。6应激状态下影响BG升高的主要相关因素为:INS(r=0.674,P<0.01),C-P(r=0.552,P<0.01),ISI(r=-0.787,P<0.01),APACHE(r=0.267,P<0.05),sTNFR(r=0.465,P<0.01)。结论SHG的主要发病环节是胰岛素抵抗。受体前急性应激激素与SHG的调节关系不明确;sTNFR对SHG有介导作用,而TNF-α、sTNFR过度释放与SHG病情程度有关。BG水平与MV时间有关,与年龄、预后和住ICU时间无关。探讨治疗和预防SHG策略的重点应放在组织对BG的利用障碍方面,提高和增强组织对INS的敏感性。

Study of relationship between stress hyperglycemia and insulin-resistance related factors

OBJECTIVE: To observe related factors in the stress hyperglycemia (SHG) of critical illness and to investigate possible pathogenesis of insulin-resistance (IR). METHODS: Blood glucose (BG), insulin (INS), C-peptide (C-P), cortisol (Cor), somatostatin (SS), glucagon (Gluc), tumor necrosis factor-alpha (TNF-alpha),soluble tumor necrosis factor receptorI (sTNFRI) andsTNFRII were determined respectively by radioimmunoassay (RIA) or enzyme linked immunoadsorbent assay (ELISA) in 47 SHG patients with critical illness and 15 healthy volunteers serving as normal controls. Their insulin sensitivity index (ISI) was calculated. RESULTS: (1)Eleven of 47 patients died, while 36 cases survived. Mean acute pathology and chronic health evaluation II (APACHEII) was (13.89+/-6.29) scores within 24 hours after admission to intensive care unit (ICU), mean days of stay in ICU was (5.5+/-6.3) days,and mean duration of mechanical ventilation (MV) was (51.49+/-66.01) hours. (2)The concentrations of INS, ISI, C-P, Cor, Gluc, TNF-alpha, sTNFRI and sTNFRII in 47 SHG patients withcritical illness were significantly higher than those in normal controls, except for SS, the differences among groups were significant (P<0.05 or P<0.01). (3)The results of analysis of severity of SHG showed that the more severe SHG was, the higher C-P and INS were, and the less prominent ISI was. (4)Analysis of scores of APACHEII in 47 cases of SHG showed that BG was not increased, but duration of MV, Cor, Gluc, SS, TNF-alpha, sTNFRI and sTNFRII were significantly increased with higher scores of APACHEII. (5)The effect of SHG was significant on MV (F=10.438,P<0.01), but not significant for outcome and days of stay in ICU. (6)The main correlative factors of BG were respectively concentrations of INS (r=0.674, P<0.01), C-P(r=0.552,P<0.01), ISI (r=-0.787, P<0.01), APACHE II(r=0.267,P<0.05) and sTNFRI(r=0.465, P<0.01). CONCLUSION: These results show that main reason of SHG in critical illness is IR. There is no strong significant correlation between acute stress hormones and the level of SHG. sTNFRIhas an influence on SHG. However, the over release of TNF-alpha and sTNFRII could be the results of seriousness of the critical illness. There is closely correlation between BG and MV, but not with the age, outcome and days of stay in ICU. The strategy of control and therapy of SHG should be alleviation of stress and improve the utilization of BG in the tissue, and increase sensitivity of INS in the tissue.