双时相门冬胰岛素30血糖控制疗效的预测因素分析A1chieve研究亚组数据

The predictive factors of good glycaemic control in Chinese patients receiving biphasic insulin aspart 30 ： a subgroup analyses from the A1 chieve study

目的分析口服降糖药物控制不佳的2型糖尿病患者的基线情况对预混胰岛素疗效的影响。方法A1chieve是一项为期24周的国际多中心、前瞻性、开放标签、非干预性的关于胰岛素类似物的研究。入选患者为经医师判断需要使用双时相门冬胰岛素30（门冬胰岛素30）的2型糖尿病患者，医师根据临床经验决定治疗方案并进行剂量调整，随访24周。主要安全性指标为：包括严重低血糖在内的严重药物不良反应（SADR）。主要疗效指标包括糖化血红蛋白（HbA1c），空腹血糖（FPG）和餐后2h血糖（2hPG）的变化。采用多因素回归分析基线因素中影响HbA1c达标的因素。结果共有4100例2型糖尿病患者起始双时相门冬胰岛素30治疗。4100例中54．2％为男性，年龄（56．2±13．6）岁。研究期间未发生SADR。治疗后HbA1c由（9．3±2．1）％下降至（7．0±1．0）％；FPG由（10．2±3．3）mmol／L下降至（6．8±1．3）mmol/L；早、午、晚餐后2hPG的变化值分别为（-5．6±4．7）、（-4．9±4．3）、（-4．2±4．1）mmol／L（P值均〈0．001）；HbA1c达标率（〈7．0％）由9．7％上升至54．2％。多因素logistic回归结果显示，基线HbA1c、FPG、2hPG与达标率呈负相关。结论较低的基线HbA1c、FPG、2hPG是口服降糖药物血糖控制不佳的中国2型糖尿病患者接受门冬胰岛素30治疗24周后HbA1c达标（〈7．0％）的预测因素。提示口服降糖药治疗失败的患者，尽早起始双时相门冬胰岛素30治疗，更有助于血糖达标。（临床试验注册号NCT00869908）

Objective To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c （ HbA1 c） 〈 7.0% in Chinese patients receiving biphasic insulin aspart 30 （ BIAsp 30 ）, who were previously inadequately controlled with oral anti-diabetic drugs （OADs）. Methods A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician＇s clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions （SADRs） including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose （FPG） , 2h post-prandial plasma glucose （2hPG） from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c 〈 7.0% after treatment were examined using multivariate analysis. Results In China,4 100 patients initiated BIAsp 30 [ 54. 2% males, age （56. 2 ± 13.6 ） years]. No SADRs were reported. Mean HbA1c was reduced from （9.3 ± 2. 1 ） % to （7.0 ± 1.0） % ; FPG was reduced from （ 10. 2 ± 3.3） mmol/L to （6. 8 ± 1.3） mmol/L. Changes in 2hPG after breakfast,lunch and dinner were （ -5.6 ± 4.7）,（ -4.9 ± 4.3） and （ -4.2 ± 4.1） mmol/L,respectively （allP〈 0. 001 ）. The proportion of patients achieving HbA1c 〈7.0% increased from 9.7% at baseline to 54. 2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbAlc, FPG, 2hPG and HbAlc 〈 7.0% after treatment. Conclusions In the Chinese subgroup of the A1 chieve study, lower baseline HbA1 c,FPG,2hPG were predictive factors for achieving HbA1 c 〈 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target.