利拉鲁肽对2型糖尿病合并低T_3综合征患者糖化血红蛋白和胰岛β细胞功能及体脂的影响分析
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摘要
目的探讨利拉鲁肽对于2型糖尿病合并低T_3综合征患者糖化血红蛋白(HbA_(1c))、胰岛β细胞功能及体脂的影响。方法将渭南市第二医院内分泌科收治的62例2型糖尿病合并低T_3综合征患者采用完全随机化方法分为实验组和对照组,两组患者保持初始二甲双胍口服降糖方案,实验组给予利拉鲁肽皮下注射,对照组给予甘精胰岛素皮下注射,分别于基线及治疗后第4、12、20、26周检测患者HbA_(1c)、胰岛β细胞功能指数(HOMA-β)、甲状腺功能(TT_3、TT_4、TSH)体重指数(BMI)及体脂率(BF﹪)。结果实验组治疗前(T0)、治疗后4周(T1)、12周(T2)、20周(T_3)、26周(T4)HbA_(1c)分别为(8.45±1.12)﹪、(7.84±0.97)﹪、(6.84±0.76)﹪、(6.90±0.80)﹪、(6.75±0.74)﹪,对照组分别为(8.51±1.04)﹪、(7.92±1.18)﹪、(7.35±0.95)﹪、(7.45±1.21)﹪、(7.24±0.12)﹪与治疗前相比,实验组(F=22.15,P<0.001)及对照组患者(F=7.52,P<0.001)HbA_(1c)显著降低,治疗后12周(T2)、20周(T_3)、26周(T4)实验组患者HbA_(1c)均显著低于对照组(t=2.33,2.11,3.63,P均小于0.05);实验组患者T0、T1、T2、T_3、T4 HOMA-β分别为85.3±42.1、100.6±43.7、124.6±67.5、130.4±53.1、124.4±43.1,对照组则为87.4±51.3、89.5±43.3、94.6±54.2、87.5±41.1、90.4±43.2,实验组显著升高(F=45.50,P<0.01),对照组无显著变化(F=0.12,P=0.9746);实验组患者T0、T1、T2、T_3、T4 TT_3分别为0.22±0.06、0.33±0.12、0.33±0.12、0.38±0.13、(0.44±0.21)ng/ml,对照组则为0.24±0.07、0.25±0.04、0.23±0.02、0.25±0.11、(0.28±0.11)ng/ml,实验组患者TT_3水平显著升高(F=11.71,P<0.01),对照组无明显变化(F=1.74,P=0.14),两组患者TT_4(实验组F=1.86,P=0.11;对照组F=1.19,P=0.31)及TSH(实验组F=0.92,P=0.45;对照组F=1.71,P=0.15)均无明显变化。实验组患者BMI及BF﹪均显著降低(F=16.52,P<0.01;F=36.80,P<0.01),对照组无统计学意义;2组均无严重不良反应,实验组低血糖发生率显著低于对照组(x~2=4.29,P=0.04)。结论对于2型糖尿病合并低T_3综合征患者,使用利拉鲁肽能够显著改善患者胰岛β细胞功能,在一定程度上升高血清TT_3水平,降低体脂率,改善胰岛素抵抗,并能达到良好的血糖控制水平,值得临床推广应用。
Objective To investigate the effect of liraglutide on glycosylated hemoglobin(HbA_(1c)), islet β cell function and body fat in type 2 diabetic patients with low T_3 syndrome.Methods Sixty-two patients with type 2 diabetes mellitus and low T_3 syndrome were randomly divided into the experimental group and the control group. The initial metformin was maintained in both groups. The experimental group received subcutaneous injection of liraglutide, while the controlgroup received insulin glargine. Gycosylated hemoglobin(HbA_(1c)), Islet beta-cell function index(HOMA-β), body mass index(BMI)and body fat percentage(BF﹪)were measured at baseline,4, 12, 20 and 26 weeks after treatment respectively. Results The levels of HbA_(1c) of the experimental group were(8.45±1.12)﹪,(7.84±0.97)﹪,(6.84±0.76)﹪,(6.90±0.80)﹪, and(6.75±0.74)﹪ at baseline, 4, 12, 20 and 26 weeks after treatment respectively, while those of the control group were(7.41±1.02)﹪,(7.92±1.18)﹪,(7.35± 0.95)﹪,(7.45±1.21)﹪, and(7.24±0.12)﹪ respectively, which decreased significantly in both groups(the experimental group: F = 22.15,P < 0.01; the control group: F = 7.52, P < 0.01). The levels of HbA_(1c) in the experimental group were significantly lower than those in the control group at 12 weeks, 20 weeks)and26 weeks. The levels of HOMA-β in patients were 85.3±42.1, 100.6±43.7, 124.6±67.5,130.4±53.1 and 124.4±43.1 at baseline, 4, 12, 20 and 26 weeks after treatment respectively(F =45.50, P < 0.01), while those of the control group were 87.4±51.3, 89.5±43.3, 94.6±54.2, 87.5±41.1 and 90.4±43.2 respectively(F = 0.12, P = 0.97). The levels of TT_3 of the experimental group were 0.22±0.06, 0.33±0.12, 0.33±0.12, 0.38±0.13 and(0.44±0.21)ng/ml respectively(F =11.71,P < 0.01), and those of the control group were 0.24±0.07, 0.25±0.04, 0.23±0.02, 0.25±0.11 and(0.28±0.11)ng/ml(F =1.74,P = 0.14)respectively. TT_4 and TSH of both groups didn't change significantly. The BMI and BF﹪ in the experimental group were significantly lowered(F = 16.52, 36.80, P < 0.01), while those in the control group didn't change. There was no serious adverse reaction in the two groups. The incidence of hypoglycemia in the experimental group was significantly lower than that in the control group(x~2 = 4.29, P = 0.04). Conclusion For type 2 diabetes patients with low T_3 syndrome, liraglutide can significantly improve the function of pancreatic islet β cells, reduce body fat rate, improve insulin resistance, and achieve good blood glucose control. Thus liraglutide may be beneficial for these patients.
Objective To investigate the effect of liraglutide on glycosylated hemoglobin(HbA_(1c)), islet β cell function and body fat in type 2 diabetic patients with low T_3 syndrome.Methods Sixty-two patients with type 2 diabetes mellitus and low T_3 syndrome were randomly divided into the experimental group and the control group. The initial metformin was maintained in both groups. The experimental group received subcutaneous injection of liraglutide, while the controlgroup received insulin glargine. Gycosylated hemoglobin(HbA_(1c)), Islet beta-cell function index(HOMA-β), body mass index(BMI)and body fat percentage(BF﹪)were measured at baseline,4, 12, 20 and 26 weeks after treatment respectively. Results The levels of HbA_(1c) of the experimental group were(8.45±1.12)﹪,(7.84±0.97)﹪,(6.84±0.76)﹪,(6.90±0.80)﹪, and(6.75±0.74)﹪ at baseline, 4, 12, 20 and 26 weeks after treatment respectively, while those of the control group were(7.41±1.02)﹪,(7.92±1.18)﹪,(7.35± 0.95)﹪,(7.45±1.21)﹪, and(7.24±0.12)﹪ respectively, which decreased significantly in both groups(the experimental group: F = 22.15,P < 0.01; the control group: F = 7.52, P < 0.01). The levels of HbA_(1c) in the experimental group were significantly lower than those in the control group at 12 weeks, 20 weeks)and26 weeks. The levels of HOMA-β in patients were 85.3±42.1, 100.6±43.7, 124.6±67.5,130.4±53.1 and 124.4±43.1 at baseline, 4, 12, 20 and 26 weeks after treatment respectively(F =45.50, P < 0.01), while those of the control group were 87.4±51.3, 89.5±43.3, 94.6±54.2, 87.5±41.1 and 90.4±43.2 respectively(F = 0.12, P = 0.97). The levels of TT_3 of the experimental group were 0.22±0.06, 0.33±0.12, 0.33±0.12, 0.38±0.13 and(0.44±0.21)ng/ml respectively(F =11.71,P < 0.01), and those of the control group were 0.24±0.07, 0.25±0.04, 0.23±0.02, 0.25±0.11 and(0.28±0.11)ng/ml(F =1.74,P = 0.14)respectively. TT_4 and TSH of both groups didn't change significantly. The BMI and BF﹪ in the experimental group were significantly lowered(F = 16.52, 36.80, P < 0.01), while those in the control group didn't change. There was no serious adverse reaction in the two groups. The incidence of hypoglycemia in the experimental group was significantly lower than that in the control group(x~2 = 4.29, P = 0.04). Conclusion For type 2 diabetes patients with low T_3 syndrome, liraglutide can significantly improve the function of pancreatic islet β cells, reduce body fat rate, improve insulin resistance, and achieve good blood glucose control. Thus liraglutide may be beneficial for these patients.
引文
1 Guariguata L,Whiting DR,Hambleton I,et al.Global estimates of diabetes prevalence for 2013 and projections for 2035[J].Diabetes Res Clin Pract,2014,103(2):137-149.
2徐小群,钟兴,杜益君,等.初诊2型糖尿病患者在不同甲状腺功能状态下的临床特点分析[J].安徽医科大学学报,2013,48(6):675-677.
3钟兴,徐小群,杜益君,等.2型糖尿病患者合并低T3综合征与糖化血红蛋白和胰岛β细胞功能相关性的研究[J].中国糖尿病杂志,2016,24(2):97-99.
4 Nauck M,Frid A,Hermansen K,et al.Efficacy and safety comparison of liraglutide,glimepiride,and placebo,all in combination with metformin,in type 2 diabetes:the LEAD(liraglutide effect and action in diabetes)-2 study[J].Diabetes Care,2009,32(1):84-90.
5 Alberti KG,Zimmet PZ.Definition,diagnosis and classification of diabetes mellitus and its complications.Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHOconsultation[J].Diabet Med,1998,15(7):539-553.
6利拉鲁肽临床研究协作组,冯凭.利拉鲁肽治疗2型糖尿病的多中心临床研究[J].国际内分泌代谢杂志,2012,32(4):217-222.
7 Selvin E,Parrinello CM,Sacks DB,et al.Trends in prevalence and control of diabetes in the United States,1988-1994 and 1999-2010[J].Ann Intern Med,2014,160(8):517-25.
8杨敬东,唐路弘.利拉鲁肽治疗2型糖尿病的疗效观察[J].中国医院药学杂志,2013,33(23):1965-1968.
9 Díez JJ,Sánchez P,Iglesias P.Prevalence of thyroid dysfunction in patients with type 2 diabetes[J].Exp Clin Endocrinol Diabetes,2011,119(4):201-207.
10 RadaidehAR,Nusier MK,Amari FL,et al.Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan[J].Saudi Med J,2004,25(8):1046-1050.
11王克永,薛丽君,王学武.二甲双胍与吡格列酮联合治疗2型糖尿病的临床观察[J].转化医学电子杂志,2016,3(7):43-44.
12 Garber A,Henry R,Ratner R,et al.Liraglutide versus glimepiride monotherapy for type 2 diabetes(LEAD-3 Mono):a randomised,52-week,phaseⅢ,double-blind,parallel-treatment trial[J].Lancet,2009,373(9662):473-481.
13陈宝琴.利拉鲁肽对肥胖的2型糖尿病患者胰岛β细胞功能指数及糖化血红蛋白的影响[J].中国实验诊断学,2013,17(11):2052-2053.
14陈频,黄勤.利拉鲁肽对三联治疗后糖化血红蛋白仍不达标2型糖尿病患者的疗效[J].中国医药导报,2015,12(9):64-68.
15陈频,黄山,徐向进,等.脐带间充质干细胞不同模式干预对2型糖尿病大鼠胰岛细胞凋亡的作用比较[J/CD].中华细胞与干细胞杂志(电子版),2016,6(1):36-41.
16刘思思,刘国强,张雪松,等.利拉鲁肽对2型糖尿病患者糖化血红蛋白、体重指数及肝脏影响的相关性分析[J].中国药物经济学,2016,11(7):40-44.
2徐小群,钟兴,杜益君,等.初诊2型糖尿病患者在不同甲状腺功能状态下的临床特点分析[J].安徽医科大学学报,2013,48(6):675-677.
3钟兴,徐小群,杜益君,等.2型糖尿病患者合并低T3综合征与糖化血红蛋白和胰岛β细胞功能相关性的研究[J].中国糖尿病杂志,2016,24(2):97-99.
4 Nauck M,Frid A,Hermansen K,et al.Efficacy and safety comparison of liraglutide,glimepiride,and placebo,all in combination with metformin,in type 2 diabetes:the LEAD(liraglutide effect and action in diabetes)-2 study[J].Diabetes Care,2009,32(1):84-90.
5 Alberti KG,Zimmet PZ.Definition,diagnosis and classification of diabetes mellitus and its complications.Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHOconsultation[J].Diabet Med,1998,15(7):539-553.
6利拉鲁肽临床研究协作组,冯凭.利拉鲁肽治疗2型糖尿病的多中心临床研究[J].国际内分泌代谢杂志,2012,32(4):217-222.
7 Selvin E,Parrinello CM,Sacks DB,et al.Trends in prevalence and control of diabetes in the United States,1988-1994 and 1999-2010[J].Ann Intern Med,2014,160(8):517-25.
8杨敬东,唐路弘.利拉鲁肽治疗2型糖尿病的疗效观察[J].中国医院药学杂志,2013,33(23):1965-1968.
9 Díez JJ,Sánchez P,Iglesias P.Prevalence of thyroid dysfunction in patients with type 2 diabetes[J].Exp Clin Endocrinol Diabetes,2011,119(4):201-207.
10 RadaidehAR,Nusier MK,Amari FL,et al.Thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan[J].Saudi Med J,2004,25(8):1046-1050.
11王克永,薛丽君,王学武.二甲双胍与吡格列酮联合治疗2型糖尿病的临床观察[J].转化医学电子杂志,2016,3(7):43-44.
12 Garber A,Henry R,Ratner R,et al.Liraglutide versus glimepiride monotherapy for type 2 diabetes(LEAD-3 Mono):a randomised,52-week,phaseⅢ,double-blind,parallel-treatment trial[J].Lancet,2009,373(9662):473-481.
13陈宝琴.利拉鲁肽对肥胖的2型糖尿病患者胰岛β细胞功能指数及糖化血红蛋白的影响[J].中国实验诊断学,2013,17(11):2052-2053.
14陈频,黄勤.利拉鲁肽对三联治疗后糖化血红蛋白仍不达标2型糖尿病患者的疗效[J].中国医药导报,2015,12(9):64-68.
15陈频,黄山,徐向进,等.脐带间充质干细胞不同模式干预对2型糖尿病大鼠胰岛细胞凋亡的作用比较[J/CD].中华细胞与干细胞杂志(电子版),2016,6(1):36-41.
16刘思思,刘国强,张雪松,等.利拉鲁肽对2型糖尿病患者糖化血红蛋白、体重指数及肝脏影响的相关性分析[J].中国药物经济学,2016,11(7):40-44.