应用动态血糖监测系统评价格列喹酮对新发2型糖尿病血糖波动的控制及其促泌作用

Effects of gliquidone treatment on glucose excursions and insulin secretions in newly diagnosed type 2 diabetic patients with continuous glucose monitoring system

目的应用动态血糖监测技术评价不同磺脲类药物控制新发2型糖尿病餐后血糖波动的作用特征，对比其胰岛素促泌作用模式的差异，并分析二者的相关性。方法选取2008年3月至12月于解放军总医院门诊就诊病程小于1年的2型糖尿病患者40例，采用随机数字表法将所有研究对象分为3组，分别给予不同磺脲类药物干预1个月：格列喹酮组16例（60mg／早，30mg／晚），格列齐特组13例（80mg／早，80mg／晚），格列苯脲组11例（2．5mg／早，2．5mg／晚）。各组研究对象在干预前后均行动态血糖监测（CGMS）和葡萄糖耐量一胰岛素释放试验（OGTF-IRT，分别在服糖前30、0min、糖负荷后15、30、45、60、120和180rain留取静脉血标本），同时采集空腹血送检各项代谢指标；对比干预前后血糖波动和胰岛素分泌特征的变化，组内治疗前后比较用配对t检验，组间比较采用方差分析。结果格列喹酮和格列奇特组干预后果糖胺较干预前分别下降了17．5％和14．8％[分别为（257±49）、（212±40）μmol／L；（2374-52）、（202±31）Ixmol／L；t=2．098、2．052，均P〈0．05]；干预后3组糖化血红蛋白水平均有下降，但差异均无统计学意义（均P〉0．05）；干预后3组的平均血糖波动幅度（MAGE）、平均血糖（MBG）、平均血糖标准差（SDBG）、最大血糖波动幅度（LAGE）、空腹血糖变异系数（CV—FPG）均较干预前有不同程度的改善（均P〈0．05），其中格列喹酮组和格列奇特组干预后MAGE降幅（分别为42．2％、36．6％）明显优于格列苯脲组的27．0％（分别为6．6±2．3，3．8±2．0；7．0±2．3，4．4±1．6；6．44-1．2，4．74-1．8；t=3．977、2．349、2．977，均P〈0．05）；干预后格列喹酮组和格列奇特组的血糖谱曲线相对平稳，血糖波动特征类似；格列苯脲组清晨空腹血糖偏低，而早餐后、晚餐后血糖升高明显强于其他2组，血糖曲线显著分离；格列喹酮干预后胰岛素分泌速率分别在30和60min达峰，120min降至基线水平；格列奇特与之非常类似；格列苯脲组胰岛素分泌速率达峰时间延迟，峰值更高，高胰岛素血症持续时间相对较长；MAGE与糖负荷后45、60min胰岛素分泌速率显著相关（r=-0．342、-0．386，均P〈0．05）。结论格列喹酮和格列奇特显著降低餐后血糖波动，改善平均血糖控制水平，与其刺激胰岛β细胞快速双峰分泌胰岛素的拟生理促泌模式有关；格列苯脲低血糖发生风险相对较大，与其强而持久的促泌作用有关。

Objective To evaluate the effectiveness of gliquidone, gliclazide and glibenclamide on postprandial glycemic variability in newly diagnosed type 2 diabetic patients with continuous glucose monitoring system （ CGMS ） , and to investigate the profile of insulin secretion. Methods A total of 40 newly diagnosed T2DM patients who received treatment in Chinese PLA General Hospital during March to December in 2008 were enrolled. All subjects randomized to receive gliquidone （ n = 16, 60 mg in the morning and 30 mg in the evening） or gliclazide（n = 13, 80 mg in the morning and 80 mg in the evening） or glibenclamide（ n = 11, 2. 5 mg in the morning and 2. 5 mg in the evening） and treated for 4 weeks. CGMS and oral glucose tolerance-insulin release test （OG3-IRT） were carried out before and after drug intervention. Results After a 4-week treatment period, serum fructosamine levels were decreased by 17.5% and 14.8% （（257±49）,（212±40）μmo1/L;（237 ＋52）,（202±31）μmol/L; t =2.098 and 2. 052 respectively, both P 〈 0.05 ） in gliquidone and glielazide group, while no significant differences were found in the mean changes of glycated hemoglobin. With drug treatment, mean amplitude of glycemic excursions （ MAGE ） , MBG （ mean blood glucose ） , SDBG （ standard deviation of MBG ） , LAGE （ large amplitude glucose excursion ） and CV-FPG （ coefficient of variation for fasting plasma glucose ） impoved significantly in all study groups （ all P 〈 0. 05 ） . And the decrease of MAGE were more significantly in gliquidone and gliclazide groups （42. 19% and 36. 61% respectively） than in glibenelamide group （27.03%）,（6.6＋2.3,3.8±2.0;7.0±2.3,4.4±1.6;6.4±1.2,4.7±1.8,respectively; t=3.977, 2. 349 and 2. 977, respectively, all P 〈 O. 05 ）. Glucose concentration curve of gliquidone and gliclazide virtually coincided with each other and were steady relatively. Fasting phases of glibenelamide ran below the other two group curves, while the breakfast and supper postprandial phases above them markedly. The characteristic of insulin secretion rate curve of gliquidone and gliclazide were also similar with each other. Moreover, the two curves both reached peak 30 rain and 60 rain after OGTT, and lowered to basal in OGTT 120 rain after OGTT, while the glibenelamide delayed the reach of the insulin secretion peak but with a higher peak value and a longer duration of byperinsulinism. Pearson correlation analysis showed that MAGE was positively correlated with insulin secretion rate 30 min and 60 rain after OGTT（ r = -0. 342, -0. 386 respectively, both P 〈 0. 05 ）. Conclusion Compared with glibenclamide, the treatment of gliquidone and glielazide may be predominant for stabilizing the postprandial blood glucose profile excursion and improving overall blood glucose levels. Gliquidone and glielazide produced a prompt bipbasie hormone release while glibenclamide induced a delayed monophasie insulin secretion. With characteristic of strong insulin secreting stimulation, glibenclamide may increase the incidence of hypoglycemia events hypoglycemia events incidence.