Monnier Louis, Mas Emilie, Ginet Christine, Michel Françoise, Villon Laetitia, Cristol Jean-Paul, Colette Claude
Department of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, Montpellier, France.
JAMA. 2006 Apr 12;295(14):1681-7. doi: 10.1001/jama.295.14.1681.
Glycemic disorders, one of the main risk factors for cardiovascular disease, are associated with activation of oxidative stress.
To assess the respective contributions of sustained chronic hyperglycemia and of acute glucose fluctuations to oxidative stress in type 2 diabetes.
DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 21 patients with type 2 diabetes (studied 2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in Montpellier, France.
Oxidative stress, estimated from 24-hour urinary excretion rates of free 8-iso prostaglandin F2alpha (8-iso PGF2alpha). Assessment of glucose fluctuations was obtained from continuous glucose monitoring system data by calculating the mean amplitude of glycemic excursions (MAGE). Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose level above preprandial values (mean postprandial incremental area under the curve [AUCpp]). Long-term exposure to glucose was estimated from hemoglobin A1c, from fasting glucose levels, and from mean glucose concentrations over a 24-hour period.
Mean (SD) urinary 8-iso PGF2alpha excretion rates were higher in the 21 patients with diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg of creatinine). In univariate analysis, only MAGE (r = 0.86; P<.001) and AUCpp (r = 0.55; P = .009) showed significant correlations with urinary 8-iso PGF2alpha excretion rates. Relationships between 8-iso PGF2alpha excretion rates and either MAGE or AUCpp remained significant after adjustment for the other markers of diabetic control in multiple linear regression analysis (multiple R2 = 0.72 for the model including MAGE and multiple R2 = 0.41 for the model including AUCpp). Standardized regression coefficients were 0.830 (P<.001) for MAGE and 0.700 (P = .003) for AUCpp.
Glucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.
血糖紊乱是心血管疾病的主要危险因素之一，与氧化应激的激活有关。
评估持续性慢性高血糖和急性血糖波动对2型糖尿病氧化应激的各自影响。
设计、地点和参与者：在法国蒙彼利埃进行的一项病例对照研究，将21例2型糖尿病患者（2003 - 2005年研究）与21例年龄和性别匹配的对照者（2001年研究）进行比较。
氧化应激，通过24小时尿游离8 - 异前列腺素F2α（8 - 异PGF2α）排泄率进行评估。通过计算血糖波动幅度平均值（MAGE）从连续血糖监测系统数据中获得血糖波动评估。通过确定餐后血糖水平高于餐前值的增量（餐后曲线下平均增量面积[AUCpp]）评估餐后对血糖不稳定的影响。通过糖化血红蛋白、空腹血糖水平以及24小时平均血糖浓度评估长期血糖暴露情况。
21例糖尿病患者的平均（标准差）尿8 - 异PGF2α排泄率（482 [206] pg/mg肌酐）高于对照组（275 [85] pg/mg肌酐）。在单因素分析中，只有MAGE（r = 0.86；P <.001）和AUCpp（r = 0.55；P =.009）与尿8 - 异PGF2α排泄率呈显著相关。在多元线性回归分析中，对糖尿病控制的其他指标进行调整后，8 - 异PGF2α排泄率与MAGE或AUCpp之间的关系仍然显著（包含MAGE的模型多元R2 = 0.72，包含AUCpp的模型多元R2 = 0.41）。MAGE的标准化回归系数为0.830（P <.001），AUCpp的标准化回归系数为0.700（P =.003）。
餐后期间以及更普遍地在血糖波动期间的血糖波动，对氧化应激的触发作用比慢性持续性高血糖更具特异性。目前的数据表明，2型糖尿病的干预试验不仅应针对糖化血红蛋白和平均血糖浓度，还应针对急性血糖波动。
