预混胰岛素转为基础胰岛素联合口服降糖药治疗方案的2型糖尿病患者的临床特征分析

Post-hoc analyses of type 2 diabetes patients switch from premixed insulin regimen to basal insulin plus oral hypoglycemic agents regimen

目的探讨每日两次预混胰岛素治疗的2型糖尿病患者转为每日一次基础胰岛素加口服降糖药的血糖控制情况与人群特征的关系及基础胰岛素的使用剂量。方法为随机、开放、两中心的平行对照研究,治疗期12周,选择每日注射两次预混胰岛素(加或不加口服降糖药治疗),空腹血糖(FBG)在7.8～16.7 mmol/L,糖化血红蛋白(HbA1c)在7%～10%的2型糖尿病患者80例,随机分至每日注射一次甘精胰岛素加格列美脲3 mg 或每日注射两次预混30 R(诺和灵)胰岛素加格列美脲3 mg 治疗组,胰岛素剂量每3天调整1次,至目标 FBG≤6.0 mmol/L。结果治疗12周后,甘精胰岛素组和预混胰岛素组的 HbA1c 均较基线水平显著下降,两组 HbA1c 下降幅度差异无统计学意义(8.8%→8.0%vs 8.9%→7.8%,P>0.05)。治疗期间,预混胰岛素组低血糖发生频率均显著高于甘精胰岛素组,总低血糖事件分别为123次、57次,经证实的低血糖例次(94 vs 21,x^2=23.692 P=0),其中午餐前低血糖发生尤其显著(64 vs 17,x^2=7.762,P=0.005)。甘精胰岛素治疗后 HbA1c≤7.5%者达28.2%(11例),剂量为(0.58±0.29)U·kg^(-1)·d^(-1);HbA1c>8.5%者占23.1%(9例),剂量为(0.66±0.30)U·kg^(-1)·d^(-1)。甘精胰岛素两亚组治疗前 HbA1c、糖尿病病程、餐后2 h C 肽水平差异均有统计学意义(分别为:8.1±0.8)% vs(9.6%±1.2)%,10年(6.0～14.5年)vs 13年(8～19.5年),餐后 C 肽:2.5 nmol/L(1.4～3.3 nmol/L)vs 1.4 nmol/L(1.2～2.6 nmol/L),均 P<0.05。结论每日2次预混胰岛素治疗的2型糖尿病患者转为每日1次甘精胰岛素联合口服降糖药治疗可以达到良好的血糖控制,治疗前 HbA1c 水平、糖尿病病程和餐后2 hC 肽水平是影响一次基础胰岛素联合口服降糖药治疗疗效的主要指标。

Objective To compare characteristics of better responders to new regimen therapy with non-responders. Methods In a 12-week, two-center, open, parallel group clinical trial, 80 type 2 diabetic patients treated with twice-daily premixed 30 R insulin with or without OAD （s） [ fasting blood glucose （ FBG ） 7.8 - 16. 7mmol/L, HbAlc 7% - 10% ] were randomized to once-daily morning insulin glargine plus glimepiride 3 mg or premixed 30 R insulin （70/30） twice-daily plus glimepiride 3 mg. Insulin dosage was titrated to target FBG ≤ 6.0 mmol/L using a three-day forced-titration algorithm. Results Mean HbAlc reduction from baseline were similar in glargine group and premixed insulin group（8. 8%→8. 0% vs 8.9%→7.8% , P 〉 0. 05）. However, hypoglycemic episodes were significantly higher in premixed-insulin-treated subjects than in glargine-treated subjects [ total： 123 vs 57; proved hypoglycemic episodes 94（76% ） vs 21 （47%） ,χ^2 = 23.692, P 〈 0. 01 ], The frequency of hypoglycemia before hunch was especially greater in premixed-insulin-treated subjects 64（52% ） vs 17 （ 30% ）, χ^2 = 7. 762, P = 0. 005. Several subjects from the premixed arm experienced too frequent hypoglycemic episodes to be recorded during 10AM - 11AM almost every day. Subgroup analysis for patients treated with glargine： 28. 2% （11 cases） of the patients in this group attained HbAlc≤7. 5% at 12 weeks. Mean daily dosage for glargine at 12 weeks were （0. 58 ± 0. 29） U·kg^-1·d^-1 in this subgroup. 23. 1% （9 cases） of the patients＇ HbAlc were 〉 8. 5% at 12 weeks, mean daily dosage for glargine were （0. 66 ± 0. 30） U·kg^-1·d^-1 . There were significant differences of baseline HbAlc, diabetes duration and baseline postprandial C-peptide between the two subgroups in glargine arm （ HbAlc ： 8. 1% ± 0. 8% vs 9. 6% ± 1.2% ; duration ： 10 （ 6 - 14. 5 ） years vs 13 （8-19.5） years; postprandial c peptide：2. 5 nmol/L （1.4-3.3） vs 1.4 （1.2-2.6） nmol/L,all P〈 0. 05 ）. Conclusion Type 2 diabetic patients treated with twice-daily injection of premixed 30 R insulin with or without OAD（s） can be effectively and safely switched to basal insulin plus OAD. Pretreatment HbAlc, diabetes duration and postprandial C peptide are the key factors that closely related to efficacy of this new regimen.