不同糖调节受损人群血糖波动与氧化应激的相关性分析

目的 采用动态血糖监测系统研究不同糖调节受损人群的血糖波动与氧化应激的相关性.方法 2008年1月至7月选取北京地区稳定人群66名,根据美国糖尿病学会(ADA)2003年标准分为正常糖耐量组(13例),糖尿病前期组(17例),2型糖尿病组(36例);所有受试对象均行72 h动态血糖临测,选取平均血糖波动幅度评价血糖波动情况;其间第48～72小时留取24 h尿,采用酶联免疫吸附法检测8-异前列腺素F2α(8-isoPGF2α)评价氧化应激水平.2型糖尿病组给予"重组赖脯胰岛素25"强化治疗12周,其间定期随访、指导生活方式干预并调整胰岛素用量.对干预前、后血糖波动、氧化应激和各项代谢指标的变化行方差分析,并对其影响因素行相关分析及多元逐步回归分析.结果 (1)基线时2型糖尿病组24 h尿游离8-isoPGF2α分泌率(8-isoPGF2α/Cr)为(1706±477)pg/mg,与糖尿病前期组(216±65)pg/mg]和正常糖耐量组(269±60)pg/mg]比较升高690%和534%,差异有统计学意义(F=27.304,P<0.05);2型糖尿病组平均血糖波动幅度(MAGE)为6.04 mmol/L,与糖尿病前期组(2.7±1.2)mmol/L]和正常糖耐量组(1.7±0.5)mmol/L]比较升高124%和249%,差异有统计学意义(F=67.729,P均<0.05).(2)2型糖尿病组经"重组赖脯胰岛素25"干预后,24 h尿8-isoPGF2α/Cr、MAGE、糖化血红蛋白、甘油三酯与干预前比较分别降低34.53%,31.81%,18.50%,28.79%,差异有统计学意义(F值分别为6.108、18.378、39.322、5.942,P均<0.05);此外,收缩压、舒张压、空腹血糖、餐后2 h血糖与干预前比较显著下降(F值分别为7.879、11.684、38.952、61.207,P均<0.01).(3)Pearson相关分析显示24 h尿8-isoPGF2α/Cr与MAGE呈显著相关(r=0.593,P<0.01);与空腹血糖(r=0.415,P<0.01)、餐后2 h 血糖(r=0.472,P<0.01)、高密度脂蛋白胆固醇(r=-0.307,P<0.01)、甘油三酯(r=0.296,P<0.01)、收缩压(r=0.268,P<0.05)显著相关;而与糖化血红蛋白无相关(r=0.186,P>0.05).(4)以24 h尿8-isoPGF2α/Cr为因变量,以上述与其有相关性的变量为自变量进行多元逐步同门分析,只有MAGE和高密度脂蛋白胆固醇进入最终方程(决定系数r2分别为0.354、0.346,P均<0.01);偏相关分析与卜述结果 一致.结论 (1)2型糖尿病组与正常糖耐昔组、糖尿病前期组比较血糖波动幅度大,氧化应激水平高;(2)2型糖尿病氧化应激活化程度与血糖波动和部分血脂代谢相关;(3)经胰岛素强化干预后,血糖波动幅度下降,氧化应激反应减轻.

Correlation of oxidative stress and acute glucose fluctuations in subtypes of impaired glucose intolerance

Objective To analyze the correlation of oxidative stress activation and acute glucose fluctuations in subtypes of impaired glucose intolerance by continuous glucose monitoring system (CGMS). Methods From January to July in 2008, assessed by repeated oral glucose tolerance test (OGTT), 30 individuals were divided into 2 groups: normal glucose tolerance (NGT, n = 13), impaired glucose regulation (IGR, n = 17). Thirty-six type 2 diabetes (T2DM) were chosen randomly in outpatients in our hospital And their blood glucose (BG) levels were monitored by CGMS for 72 h. Intraday glycemie 9fluctuation were assessed by mean amplitude of glucose excursions (MAGE) ; From 48 h to 72 h duringCGMS period, 24 h urine samples were collected and free 8-iso prostaglandin F2α (8-isoPGF2α) were measured by ELISA to evaluate oxidative stress. Repeated CGMS were given after three months insulin Lispro 25 intensive interventions in T2DM group. Periodical interview included life style intervention and insulin regulations. Glucose excursions and other metabolic readouts before and after intervention were compared by one-way ANOVA. Possible factors effected on the activations of oxidative stress and glucose excursions were analyzed by Pearson correlation coefficient and multivariate stepwise regression. Results (1) Mean(SD) urinary excretion rates of 8-isoPGF2α (1706±477) pg/mg of creatinine in T2DM group significantly increased by 690% and 534% compared with it in IGR group ((216±65) pg/mg) and NGT group ((269±60) pg/mg) (F = 27.304, P < 0.05). And levels of M AGE(6.04 mmol/L) in T2DM group also elevated by 124% and 249% compared with those in IGR group ((2.7±1.2) mmol/L) and NGT group ((1.7 ± 0.5) mmol/L) (F = 67.729, P < 0.05). (2) With insulin intensive interventions in T2DM group, urinary excretion rates of 8-isoPGF2α, MAGE, glycosylated hemoglobin (HbA1c) and triglyceride (TG) readouts decreased by 34.53%, 31.81% , 18.50% and 28.79% respectively (F value equal to 6.108, 18.378, 39.322, 5.942 respectively, all P < 0.05). Moreover, the level of systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose(FBG) and 2 h postprandial blood glucose (2 h PBG) also significantly decreased(F value equal to 7.879,11.684, 38.952 and 61.207 respectively, all P < 0.01). (3)Pearson correlation analysis:urinary excretion rates of 8-isoPGF2α was positively correlated with MAGE (r=0.593,P <0.01) , FBG(r =0.415,P <0.01), 2 h PBG(r =0.472,P<0.01), high density lipoprotein cholesterol(HDL-C) (r = -0.307, P < 0.01), TG (r = 0.296, P <0.01) and SBP (r =0.268 ,P < 0.05). However, no significant correlation were found between HbAlc and urinary excretion rates of 8-isoPGF2α (r = 0.186, P > 0.05). (4) Using urinary excretion rates of 8-isoPGF2α as dependent, and positive correlation factors above-mentioned as independent, multivariate stepwise regression analysis showed MAGE and HDL-C entered final two models (r2 value was 0.354 and 0.346 respectively, all P < 0.01); and same results were found by Partial correlation analysis. Conclusion (1) With the deterioration of glucose regulation, the blood glucose excursions become increasingly fluctuant and oxidative stress become more activity. (2)The activation of oxidative stress in T2DM is positively correlated with glucose fluctuations and some lipoprotein metabolism. (3) With insulin intensive treatment, both glucose excursions and oxidative stress are improved obviously.