应用动态血糖监测及高胰岛素-正糖钳夹技术评价地特胰岛素对2型糖尿病患者的疗效及安全性

Efficacy and safety of insulin detemir in type 2 diabetes patients by the combined application of continuous glucose monitoring system and hyperinsulinemic-euglycemic clamp technique

目的 应用动态血糖监测（CGM）、高胰岛素-正糖钳夹技术以及静脉葡萄糖耐量试验（IVGTT）评价口服降糖药控制不佳的2型糖尿病患者加用地特胰岛素皮下注射的疗效、安全性以及对血糖波动、病理生理功能的影响.方法选取2010年3月至8月于大连市中心医院就诊的20例口服降糖药控制不佳的2型糖尿病患者（均符合1999年WHO糖尿病诊断标准）,在原有治疗方案的基础上加用地特胰岛素（6~8）U/d起始治疗,治疗期为3个月,治疗前后分别应用动态血糖监测技术及高胰岛素-正糖钳夹技术以及IVGTT评估患者的血糖波动、胰岛素敏感性以及第1时相胰岛素分泌的情况,测定20例患者治疗前后基线身高、体重、腰围、臀围、肝肾功能、血糖、血脂、胰岛素及C肽、糖化血红蛋白（HbA1c）等指标,同时比较治疗前后的相关指标.正态分布的计量资料比较采用t检验,非正态分布的计量资料采用秩和检验;相关分析采用Pearson相关及多元线性回归分析.结果 经过3个月的治疗,患者HbA1c、腰臀比、总胆固醇、低密度脂蛋白胆固醇较前明显下降[分别为（8.8±1.6）%,（7.6±1.3）%,t=4.830,P〈0.001;0.95 ± 0.04,0.94 ± 0.04,t=2.317,P〈0.05;（5.1±0.6）mmol/L,（4.5±0.9）mmol/L,t=3.459,P〈0.01;（3.2±0.8） mmol/L,（2.6±0.8） mmol/L,t=3.822,P〈0.01].治疗后正糖钳夹中葡萄糖利用率较前明显升高[（3.9 ±2.1）mg·min^-1·kg^-1,（5.0±2.4） mg·min^-1·kg^-1,t=-2.269,P〈0.05].采用IVGTT刺激后的急性胰岛素反应反映第1时相,治疗后AIR较前有所恢复,但差异无统计学意义.治疗后动态血糖监测显示的平均血糖波动幅度较前明显下降[（7.3±2.4）mmol/L,（5.4±2.9）mmol/L,t=2.279,P〈0.05],而日间平均血糖绝对差治疗前后差异无统计学意义（P〉0.05）.治疗期间无严重低血糖发生.结论 口服药控制不佳的2型糖尿病加用地特胰岛素治疗,在有效地控制血糖的同时,能减轻血糖波动,改善胰岛素敏感性.

Objective To evaluate efficacy, safety and effect of glycemic excursion of once-daily insulin detemir added to oral antidiabetic drugs in poorly controlled type 2 diabetes patients by continuous glucose monitoring system（CGMS） and Hyperinsulinemic-euglycemic Clamp Technique. Methods 20 type 2 diabetes patients with poor glycemic control by oral antidiabetic drugs were added to receive once-daily bedtime insulin detemir injection. The observation lasted for three months. The parameters were measured before and after treatment included M value, AIR, MAGE, MODD by continuous glucose monitoring system（CGMS） and Hyperinsulinemic-euglycemic Clamp Technique. The parameters included BMI, TC, TG, LDL, HDL, C-P and HbA1c also were measured before and after treatment. Data analysis were performed using SPSS 16.0. Results After 3 months′ treatment, HbA1c, WHR, TC, LDL were significantly decreased than before, respectively（（8.8±1.6）%,（7.6±1.3）%, t=4.830, P〈0.001;（0.95±0.04）mmol/L,（0.94±0.04）mmol/L, t=2.317,P〈0.05;（5.1±0.6） mmol/L,（4.5±0.9） mmol/L, t=3.459, P〈0.01;（3.2±0.8） mmol/L, （2.6±0.8） mmol/L,t=3.822,P〈0.01） M value was significantly increased than before （（3.9±2.1） mg·min^-1·kg^-1,（5.0±2.4）mg·min^-1·kg^-1, t=-2.269,P〈0.05）, AIR was also increased but no statistical difference. Detemir treatment also obviously reduced MAGE from （7.3 ± 2.4）mmol/L to（5.4±2.9）mmol/L, there were significances in statistics. But there was no statistical difference in MODD after treatment. After detemir treatment, the value of weight was decreased than before, but with no statistical difference.There was no serious hypoglycemia. ConclusionOnce-daily insulin detemir added to oral antidiabetic drugs in poorly controlled type 2 diabetes patients could improved glycemic control, the insulin sensitivity and reduced glycemic.