不同抗糖尿病治疗方案对2型糖尿病患者血小板功能的影响
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摘要
目的观察不同的治疗方法(格列吡嗪、吡格列酮、胰岛素)对2型糖尿病患者血小板功能的影响。方法将新近诊断的二甲双胍治疗效果不佳的60例2型糖尿病患者随机分为3组:A组:格列吡嗪组,在原二甲双胍(1.5g/日)基础上加用格列吡嗪(5-10mg/日);B组:吡格列酮组,在原口服二甲双胍(1.5g/日)基础上加用吡格列酮(15-30mg/日);C组:注射胰岛素组,在原口服二甲双胍基础上每日注射胰岛素(给药方式、剂量个体化)。另外取R组:20例初发的2型糖尿病患者予以单纯胰岛素强化治疗,以及N组:健康对照20例。在研究开始时检测各组的FBG、HbA1C以及反映血小板活化状态的各个指标,包括血小板膜上GMP-140、PAC-1的表达率,ADP诱导的血小板的聚集率。治疗两周后再次测定R组的上述各指标,并与其0周时进行统计学比较。开始治疗后4周、24周时分别测定A、B、C组血小板的活化状态,分别与各组0周时进行统计学比较,并且进行A、B、C组组间的统计学比较。
结果
①基线时A、B、C组的FBG、HbA1C、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率无显著性差异(P﹥0.05)。
②在基线时R组FBG、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率均明显高于N组,差异有统计学意义(P﹤0.01)。
③治疗2周后,R组FBG、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率均明显低于基线时,差异有统计学意义(P〈0.01)。
④治疗4周后,A、C组间FBG差异无统计学意义(P﹥0.05),B组FBG高于A、C组,差异有统计学意义(P﹤0.01)。
⑤治疗4周后,A、B、C组间ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率差异无统计学意义(P>0.05)。
⑥治疗24周后,A、C组间FBG、HbA1C差异无统计学意义(P﹥0.05),B组FBG高于A、C组,差异有统计学意义(P﹤0.01), HbA1C高于A、C组,差异有统计学意义(P〈0.05)。
⑦治疗24周后,A、C组间ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率差异无统计学意义(P﹥0.05)。B组ADP诱导的血小板聚集率低于A、C组,差异有统计学意义(P﹤0.01)。B组血小板GMP-140的表达率低于A、C组,差异有统计学意义(P﹤0.05),B组PAC-1的表达率低于A组(P﹤0.01),亦低于C组(P﹤0.05)。
结论不同的抗糖尿病治疗方法在降低血糖的同时均能改善2型糖尿病患者的血小板功能。其中吡格列酮降低血小板功能效果优于格列吡嗪和胰岛素,可能具有不依赖于降血糖的抑制2型糖尿病血小板功能的作用。
Objectives: To observe the influence of different therapies (glipizide,pioglitazone, insulin)on the function of type 2 diabetic patients’platelets. Methods: 60 recent diagnosed type 2 diabetic patients who had been treated ineffectively with Metformin were divided randomly into three groups:Group A: it refers to Group of Glipizide,which means to add glipizide(5-10mg/day) on the former treatment of Metformin(1.5g/day);Group B: it refers to Group of Pioglitazone,which means to add pioglitazone(15-30mg/day) on the former treatment of Metformin(1.5g/day);Group C:it stands for Group of Insulin-injection,which means to add insulin injection( with individualized dosage) on the former treatment of Metformin. Besides, to set up a Group R: this group consists of 20 newly diagnosed type 2 diabetic patients, and to give this group of patients intensified therapy with insulin. Group N: 20 matched healthy control subjects. At the beginning of the study, FBG, HbA1C, expression ratio of GMP-140,PAC-1 on the platelet membrane, and the packing fraction of the platelets derived by ADP were measured in all the subjects. Two weeks later, we detected variables above mentioned in Group R, and compared the result with the index detected in week 0 on the theory of statistics. In addition, the platelet activation of group A, group B, and group C were measured in week 4 and week 24, and compared with the results inspected in week 0 separatly, as well as to make comparison among group A, group B, and group C.
Results:
①On the baseline, there no significant difference among group A, group B and group C’s FBG、HbA1C, their packing fractions of the platelets derived by ADP, and their express ratios of GMP-140、PAC-1 on the platelet membrane(P﹥0.05).
②At the baseline, FBG、HbA1C, its packing fraction of the platelets derived by ADP, as well as its express ratio of GMP-140、PAC-1 on the platelet membrane in group R were all obviously higher than those in Group N , and those differences were statistically significant(P﹤0.01).
③Two weeks after been treated, group R’s FBG、the packing fraction of the platelets derived by ADP, and the express ratio of GMP-140、PAC-1 on the platelet membrane are lower than those on the baseline,as well, with a statistical significance( P〈0.01).
④Four weeks after been treated,the differences of FBG between group A and group C has no statistical significance(P﹥0.05), the FBG of group B was higher than that of group A and group C with a statistical significance: P﹤0.01.
⑤Four weeks after been treated, the differences of the packing fraction of the blood platelets derived by ADP, and the express ratio of GMP-140、PAC-1 on the platelet membrane had no statistical meaning (P>0.05) among group A, group B and group C.
⑥24 weeks after been treated,the differences of FBG、HbA1 between group A and group C had no statistical significance(P﹥0.05),the FBG in group B was higher than that of group A and group C, with a statistical significance of P﹤0.01, the HbA1C was also higher than that in group A and group C, the difference had statistical meaning(P〈0.05〉.
⑦24 weeks after been treated,the difference of the packing fraction of the platelets derived by ADP and the express ratio of GMP-140、PAC-1 on the platelet membrane between group A and group C had no statistical meaning(P﹥0.05). The packing fraction of the platelets derived by ADP in group B was lower than that in group A and group C, with a statistical significance of P﹤0.01, the expression ratio of GMP-140 of group B was lower than that of group A and group C, with a statistical meaning of P﹤0.05, and expression ratio of PAC-1 in group B not only lower than that of group A(P﹤0.01),but also lower than that of group C(P﹤0.05).
Conclusion Different anti-diabetes therapies can cut down the blood glucose, at the same time; they can supress the platelet function of type 2 diabetic patients. What’s more, the Pioglitazone is more effective than the Glipizide and Insulin in lowering enhanced platelet function; which is independent of its effect on lowing blood glucose.
结果
①基线时A、B、C组的FBG、HbA1C、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率无显著性差异(P﹥0.05)。
②在基线时R组FBG、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率均明显高于N组,差异有统计学意义(P﹤0.01)。
③治疗2周后,R组FBG、ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率均明显低于基线时,差异有统计学意义(P〈0.01)。
④治疗4周后,A、C组间FBG差异无统计学意义(P﹥0.05),B组FBG高于A、C组,差异有统计学意义(P﹤0.01)。
⑤治疗4周后,A、B、C组间ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率差异无统计学意义(P>0.05)。
⑥治疗24周后,A、C组间FBG、HbA1C差异无统计学意义(P﹥0.05),B组FBG高于A、C组,差异有统计学意义(P﹤0.01), HbA1C高于A、C组,差异有统计学意义(P〈0.05)。
⑦治疗24周后,A、C组间ADP诱导的血小板聚集率、血小板GMP-140、PAC-1的表达率差异无统计学意义(P﹥0.05)。B组ADP诱导的血小板聚集率低于A、C组,差异有统计学意义(P﹤0.01)。B组血小板GMP-140的表达率低于A、C组,差异有统计学意义(P﹤0.05),B组PAC-1的表达率低于A组(P﹤0.01),亦低于C组(P﹤0.05)。
结论不同的抗糖尿病治疗方法在降低血糖的同时均能改善2型糖尿病患者的血小板功能。其中吡格列酮降低血小板功能效果优于格列吡嗪和胰岛素,可能具有不依赖于降血糖的抑制2型糖尿病血小板功能的作用。
Objectives: To observe the influence of different therapies (glipizide,pioglitazone, insulin)on the function of type 2 diabetic patients’platelets. Methods: 60 recent diagnosed type 2 diabetic patients who had been treated ineffectively with Metformin were divided randomly into three groups:Group A: it refers to Group of Glipizide,which means to add glipizide(5-10mg/day) on the former treatment of Metformin(1.5g/day);Group B: it refers to Group of Pioglitazone,which means to add pioglitazone(15-30mg/day) on the former treatment of Metformin(1.5g/day);Group C:it stands for Group of Insulin-injection,which means to add insulin injection( with individualized dosage) on the former treatment of Metformin. Besides, to set up a Group R: this group consists of 20 newly diagnosed type 2 diabetic patients, and to give this group of patients intensified therapy with insulin. Group N: 20 matched healthy control subjects. At the beginning of the study, FBG, HbA1C, expression ratio of GMP-140,PAC-1 on the platelet membrane, and the packing fraction of the platelets derived by ADP were measured in all the subjects. Two weeks later, we detected variables above mentioned in Group R, and compared the result with the index detected in week 0 on the theory of statistics. In addition, the platelet activation of group A, group B, and group C were measured in week 4 and week 24, and compared with the results inspected in week 0 separatly, as well as to make comparison among group A, group B, and group C.
Results:
①On the baseline, there no significant difference among group A, group B and group C’s FBG、HbA1C, their packing fractions of the platelets derived by ADP, and their express ratios of GMP-140、PAC-1 on the platelet membrane(P﹥0.05).
②At the baseline, FBG、HbA1C, its packing fraction of the platelets derived by ADP, as well as its express ratio of GMP-140、PAC-1 on the platelet membrane in group R were all obviously higher than those in Group N , and those differences were statistically significant(P﹤0.01).
③Two weeks after been treated, group R’s FBG、the packing fraction of the platelets derived by ADP, and the express ratio of GMP-140、PAC-1 on the platelet membrane are lower than those on the baseline,as well, with a statistical significance( P〈0.01).
④Four weeks after been treated,the differences of FBG between group A and group C has no statistical significance(P﹥0.05), the FBG of group B was higher than that of group A and group C with a statistical significance: P﹤0.01.
⑤Four weeks after been treated, the differences of the packing fraction of the blood platelets derived by ADP, and the express ratio of GMP-140、PAC-1 on the platelet membrane had no statistical meaning (P>0.05) among group A, group B and group C.
⑥24 weeks after been treated,the differences of FBG、HbA1 between group A and group C had no statistical significance(P﹥0.05),the FBG in group B was higher than that of group A and group C, with a statistical significance of P﹤0.01, the HbA1C was also higher than that in group A and group C, the difference had statistical meaning(P〈0.05〉.
⑦24 weeks after been treated,the difference of the packing fraction of the platelets derived by ADP and the express ratio of GMP-140、PAC-1 on the platelet membrane between group A and group C had no statistical meaning(P﹥0.05). The packing fraction of the platelets derived by ADP in group B was lower than that in group A and group C, with a statistical significance of P﹤0.01, the expression ratio of GMP-140 of group B was lower than that of group A and group C, with a statistical meaning of P﹤0.05, and expression ratio of PAC-1 in group B not only lower than that of group A(P﹤0.01),but also lower than that of group C(P﹤0.05).
Conclusion Different anti-diabetes therapies can cut down the blood glucose, at the same time; they can supress the platelet function of type 2 diabetic patients. What’s more, the Pioglitazone is more effective than the Glipizide and Insulin in lowering enhanced platelet function; which is independent of its effect on lowing blood glucose.
引文
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