口服降糖药血糖控制不佳2型糖尿病患者联合1次胰岛素治疗方案的探讨
|
摘要
目的探讨2型糖尿病(T2D)患者口服降糖药(OAD)血糖控制不佳时联合1次胰岛素治疗的方案(1+OAD)选择。方法回顾性分析于汕头大学医学院第二附属医院2017年6月至2018年9月门诊就诊的T2D患者共71例,其原有降糖方案为磺脲类联合二甲双胍>3个月(均已增加至次大推荐剂量)血糖仍未达标,根据加用胰岛素剂型不同分为预混组和甘精组。预混组41例:晚餐前加用人预混胰岛素;甘精组30例:睡前加用甘精胰岛素。回顾12周治疗记录;比较加用胰岛素前(基线)和加用胰岛素12周后2组糖化血红蛋白(HbA1c)、空腹血糖(FPG)、体质量;比较2组平均胰岛素用量、低血糖事件,餐后2 h血糖(PPG)及睡前血糖。结果预混组基线和加用胰岛素12周后HbA1c分别为(8.52±0.77)%和(7.10±0.56)%,FPG分别为(9.72±1.27)mmol·L~(-1)和(6.81±0.78)mmol·L~(-1);甘精组基线和加用胰岛素12周后HbA1c分别为(8.41±0.70)%和(7.20±0.52)%,FPG分别为(9.63±1.48)mmol·L~(-1)和(6.87±0.64)mmol·L~(-1)。与基线比较,加用胰岛素12周后预混组和甘精组HbA1c(t=18.22,P=0.000;t=11.80,P=0.000)、FPG(t=18.50,P=0.000;t=12.68,P=0.000)均有明显下降;加用胰岛素12周后2组HbA1c、FPG下降幅度比较差异无统计学意义(t=-0.78,P=0.44;t=-0.35,P=0.73)。2组HbA1c达标率(HbA1c<7%)比较差异无统计学意义(χ~2=0.167,P=0.81)。预混组平均胰岛素用量为(0.28±0.06)U·kg~(-1),甘精组平均胰岛素用量为(0.29±0.08)U·kg~(-1),2组比较差异无统计学意义(t=-0.881,P=0.38)。预混组体质量平均增加(0.27±0.54)kg,甘精组体质量平均增加(0.37±0.45)kg,2组比较差异无统计学意义(t=-0.81,P=0.42)。2组均未发现严重低血糖事件,2组低血糖事件比较差异无统计学意义(χ~2=0.79,P=0.42)。2组PPG比较差异无统计学意义(t=-0.31,P=0.75),而预混组睡前血糖明显低于甘精组(t=-5.71,P=0.000)。结论对于口服磺脲类联合二甲双胍血糖控制不佳的T2D患者,在一定的血糖范围内,晚餐前加用1针预混胰岛素,与加用1针甘精胰岛素对比,胰岛素用量及降低FPG、HbA1c的效果相当,无增加低血糖风险,而预混组对控制晚餐后血糖效果更优。
Objective To discuss the scheme of once-daily insulin combination therapy in patients with type 2 diabetes(T2 D) inadequately controlled with oral antidiabetic drugs(OAD).Methods A retrospective analysis was made on 71 T2 D patients treated in our hospital from June 2017 to September 2018.The original antidiabetic regimen was sulfonylurea combined with metformin for more than 3 months(drugs had been increased to the second highest recommendation doses).Due to blood glucose levels were still above the normal range,these patients were additionally given either human premixed insulin before dinner(premixed group,41 cases) or insulin glargine at bedtime(glargine group,30 cases).The 12-week treatment records were reviewed.Fasting blood glucose(FPG),hemoglobin HbA1 c and body weight were measured before and after treatment with insulin for 12 weeks.Insulin dosage,hypoglycemic events and levels of 2-hour postprandial blood glucose(PPG) and pre-bedtime blood glucose were compared between the two groups.ResultsThe HbA1 c and FPG levels were,respectively,(8.52±0.77)% and(9.72±1.27)mmol·L~(-1) in premixed group and(8.41±0.70)% and(9.63±1.48)mmol·L~(-1) in glargine group before insulin treatment,and(7.10±0.56)% and(6.81±0.78)mmol·L~(-1) in premixed group and(7.20±0.52)% and(6.87±0.64)mmol·L~(-1) in glargine group after 12 weeks of treatment.After treatment with insulin for 12 weeks,HbA1 c and FPG levels obviously decreased in both premixed group(t=18.22 and 18.50,respectively;P=0.000) and glargine group(t=11.80 and 12.68,respectively;P=0.000),but the decrease was not different between the two groups(t=-0.78 and-0.35,respectively;P=0.44 and 0.73,respectively).Furthermore,there were no significant differences between the two groups in the rate of HbA1 c<7%(χ~2=0.167,P=0.81),average insulin dosage((0.28±0.06) U·kg~(-1) vs(0.29±0.08) U·kg~(-1),t=-0.881,P=0.38),average weight gain((0.27±0.54)kg vs(0.37±0.45) kg,t=-0.81,P=0.42),hypoglycemic events(χ~2=0.79,P=0.42),and PPG levels(t=-0.31,P=0.75).No serious hypoglycemic events were found in both groups.The pre-bedtime blood glucose levels in premixed group were lower than those in glargine group(t=-5.71,P=0.000).Conclusion Once-daily injection of human premixed insulin before dinner has the same efficacy as that of insulin glargine at bedtime in insulin dosage and reduction of HbA1 c and FPG levels,and neither of them can increase the risk of hypoglycemia in T2 D patients inadequately controlled with oral OAD.However,human premixed insulin is superior insulin glargine for post-dinner blood glucose control.
Objective To discuss the scheme of once-daily insulin combination therapy in patients with type 2 diabetes(T2 D) inadequately controlled with oral antidiabetic drugs(OAD).Methods A retrospective analysis was made on 71 T2 D patients treated in our hospital from June 2017 to September 2018.The original antidiabetic regimen was sulfonylurea combined with metformin for more than 3 months(drugs had been increased to the second highest recommendation doses).Due to blood glucose levels were still above the normal range,these patients were additionally given either human premixed insulin before dinner(premixed group,41 cases) or insulin glargine at bedtime(glargine group,30 cases).The 12-week treatment records were reviewed.Fasting blood glucose(FPG),hemoglobin HbA1 c and body weight were measured before and after treatment with insulin for 12 weeks.Insulin dosage,hypoglycemic events and levels of 2-hour postprandial blood glucose(PPG) and pre-bedtime blood glucose were compared between the two groups.ResultsThe HbA1 c and FPG levels were,respectively,(8.52±0.77)% and(9.72±1.27)mmol·L~(-1) in premixed group and(8.41±0.70)% and(9.63±1.48)mmol·L~(-1) in glargine group before insulin treatment,and(7.10±0.56)% and(6.81±0.78)mmol·L~(-1) in premixed group and(7.20±0.52)% and(6.87±0.64)mmol·L~(-1) in glargine group after 12 weeks of treatment.After treatment with insulin for 12 weeks,HbA1 c and FPG levels obviously decreased in both premixed group(t=18.22 and 18.50,respectively;P=0.000) and glargine group(t=11.80 and 12.68,respectively;P=0.000),but the decrease was not different between the two groups(t=-0.78 and-0.35,respectively;P=0.44 and 0.73,respectively).Furthermore,there were no significant differences between the two groups in the rate of HbA1 c<7%(χ~2=0.167,P=0.81),average insulin dosage((0.28±0.06) U·kg~(-1) vs(0.29±0.08) U·kg~(-1),t=-0.881,P=0.38),average weight gain((0.27±0.54)kg vs(0.37±0.45) kg,t=-0.81,P=0.42),hypoglycemic events(χ~2=0.79,P=0.42),and PPG levels(t=-0.31,P=0.75).No serious hypoglycemic events were found in both groups.The pre-bedtime blood glucose levels in premixed group were lower than those in glargine group(t=-5.71,P=0.000).Conclusion Once-daily injection of human premixed insulin before dinner has the same efficacy as that of insulin glargine at bedtime in insulin dosage and reduction of HbA1 c and FPG levels,and neither of them can increase the risk of hypoglycemia in T2 D patients inadequately controlled with oral OAD.However,human premixed insulin is superior insulin glargine for post-dinner blood glucose control.
引文
[1] 中华医学会糖尿病学分会.中国2型糖尿病防治指南:2017年版[J].中华糖尿病杂志,2018,10(1):4-13.
[2] MARATHE P H,GAO H X,CLOSE K L.American Diabetes Association Standards of Medical Care in Diabetes 2017[J].J Diabetes,2017,9(4):320-324.
[3] GARBER A J,ABRAHAMSON M J,BARZILAY J I,et al.Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management:2017 summary[J].Endocr Pract,2017,23(2):207-238.
[4] 中华医学会糖尿病学分会,中国医师协会营养医师专业委员会.中国糖尿病医学营养治疗指南[M].北京:人民军医出版社,2010:18-31,146-155.
[5] 母义明,纪立农,宁光,等.二甲双胍临床应用专家共识:2016年版[J].药品评价,2016,13(19):5-18.
[6] NO AUTHORS LISTED.Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes(UKPDS 34).UK Prospective Diabetes Study(UKPDS) Group[J].Lancet,1998,352(9131):854-865.
[7] WENG W,LIANG Y,KIMBALL E S,et al.Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases,2007 vs 2012:findings from a large US healthcare claims database analysis[J].J Med Econ,2016,19(7):655-662.
[8] 纪立农,陆菊明,朱大龙,等.成人2型糖尿病基础胰岛素临床应用中国专家指导建议[J].中国糖尿病杂志,2017,25(1):2-9.
[9] HORVATH K,JEITLER K,BERGHOLD A,et al.Long-acting insulin analogues versus NPH insulin(human isophane insulin) for type 2 diabetes mellitus[J].Cochrane Database Syst Rev,2007,18(2):CD005613.
[10] LIGTHELM R J,GYLVIN T,DELUZIO T,et al.A comparison of twice-daily biphasic insulin aspart 70/30 and once-daily insulin glargine in persons with type 2 diabetes mellitus inadequately controlled on basal insulin and oral therapy:a randomized,open-label study[J].Endocr Pract,2011,17(1):41-50.
[11] GARBER A J,WAHLEN J,WAHL T,et al.Attainment of glycaemic goals in type 2 diabetes with once-,twice-,or thrice-daily dosing with biphasic insulin aspart 70/30(The 1-2-3 study)[J].Diabetes Obes Metab,2006,2006,8(1):58-66.
[12] YANG W Y,JI Q H,ZHU D L,et al.Biphasic insulin aspart 30 three times daily is more effective than a twice-daily regimen,without increasing hypoglycemia,in Chinese subjects with type 2 diabetes inadequately controlled on oral antidiabetes drugs[J].Diabetes Care,2008,31(5):852-856.
[13] HOLMAN R R,THORNE K I,FARMER A J,et al.Addition of biphasic,prandial,or basal insulin to oral therapy in type 2 diabetes[J].N Engl J Med,2007,357(17):1716-1730.
[14] 缪从庆,孟信龙,樊爱娟,等.体质量指数和C肽增值在血糖控制不佳的2型糖尿病患者强化降糖后方案调整中的应用[J].中华内分泌代谢杂志,2017,33(7):548-551.
[2] MARATHE P H,GAO H X,CLOSE K L.American Diabetes Association Standards of Medical Care in Diabetes 2017[J].J Diabetes,2017,9(4):320-324.
[3] GARBER A J,ABRAHAMSON M J,BARZILAY J I,et al.Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management:2017 summary[J].Endocr Pract,2017,23(2):207-238.
[4] 中华医学会糖尿病学分会,中国医师协会营养医师专业委员会.中国糖尿病医学营养治疗指南[M].北京:人民军医出版社,2010:18-31,146-155.
[5] 母义明,纪立农,宁光,等.二甲双胍临床应用专家共识:2016年版[J].药品评价,2016,13(19):5-18.
[6] NO AUTHORS LISTED.Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes(UKPDS 34).UK Prospective Diabetes Study(UKPDS) Group[J].Lancet,1998,352(9131):854-865.
[7] WENG W,LIANG Y,KIMBALL E S,et al.Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases,2007 vs 2012:findings from a large US healthcare claims database analysis[J].J Med Econ,2016,19(7):655-662.
[8] 纪立农,陆菊明,朱大龙,等.成人2型糖尿病基础胰岛素临床应用中国专家指导建议[J].中国糖尿病杂志,2017,25(1):2-9.
[9] HORVATH K,JEITLER K,BERGHOLD A,et al.Long-acting insulin analogues versus NPH insulin(human isophane insulin) for type 2 diabetes mellitus[J].Cochrane Database Syst Rev,2007,18(2):CD005613.
[10] LIGTHELM R J,GYLVIN T,DELUZIO T,et al.A comparison of twice-daily biphasic insulin aspart 70/30 and once-daily insulin glargine in persons with type 2 diabetes mellitus inadequately controlled on basal insulin and oral therapy:a randomized,open-label study[J].Endocr Pract,2011,17(1):41-50.
[11] GARBER A J,WAHLEN J,WAHL T,et al.Attainment of glycaemic goals in type 2 diabetes with once-,twice-,or thrice-daily dosing with biphasic insulin aspart 70/30(The 1-2-3 study)[J].Diabetes Obes Metab,2006,2006,8(1):58-66.
[12] YANG W Y,JI Q H,ZHU D L,et al.Biphasic insulin aspart 30 three times daily is more effective than a twice-daily regimen,without increasing hypoglycemia,in Chinese subjects with type 2 diabetes inadequately controlled on oral antidiabetes drugs[J].Diabetes Care,2008,31(5):852-856.
[13] HOLMAN R R,THORNE K I,FARMER A J,et al.Addition of biphasic,prandial,or basal insulin to oral therapy in type 2 diabetes[J].N Engl J Med,2007,357(17):1716-1730.
[14] 缪从庆,孟信龙,樊爱娟,等.体质量指数和C肽增值在血糖控制不佳的2型糖尿病患者强化降糖后方案调整中的应用[J].中华内分泌代谢杂志,2017,33(7):548-551.