【摘要】 目的探讨利拉鲁肽（LIR）和甘精胰岛素（GLA）对男性2型糖尿病（T2DM）患者骨代谢的影响。方法选取2018年1至6月浙江省人民医院收治的单用磺脲类促泌剂（SU）和（或）α-糖苷酶抑制剂（AGI）血糖控制不佳的男性T2DM患者99例,采用随机数字表法分为LIR治疗组[LIR联合SU和（或）AGI,LIR组]、GLA治疗组[GLA联合SU和（或）AGI,GLA组]与口服降糖药物治疗组[SU和（或）AGI,OAD组],随访48周,治疗前、治疗24周及48周分别测定患者一般生化指标:FPG、餐后2 h血糖（2h-PBG）、糖化血红蛋白(HbA_1C)、BMI、TG、LDL-C;骨转换指标:骨钙素（OC）、Ⅰ型前胶原氨基端原肽（P1NP）、Ⅰ型胶原羧基端肽β特殊序列（β-CTX）、25-羟维生素D₃（25-OH-D₃）,治疗前、治疗48周采用双能X线骨密度仪测定所有患者股骨颈、髋关节、腰椎（L₁～L₄）骨密度（BMD）,对比治疗前后一般生化指标、骨转换指标、BMD及不良反应发生情况。结果 99例中有90例患者完成48周随访,各组均为30例。3组患者治疗24、48周FPG、2h-PBG、HbA_1C、TG均较治疗前显著下降（均P<0.01）。3组患者治疗24周2h-PBG、HbA_1C、BMI、LDL-C比较差异均有统计学意义（均P<0.05）,而FPG、TG比较差异均无统计学意义（均P>0.05）。3组患者治疗48周2h-PBG、BMI、LDL-C比较差异均有统计学意义（均P<0.05）,而FPG、HbA_1C、TG比较差异均无统计学意义（均P>0.05）。LIR组治疗48周后LDL-C与治疗24周比较差异有统计学意义（P<0.05）。治疗24及48周LIR组BMI、2h-PBG、LDL-C均低于GLA组及OAD组（均P<0.05）。3组患者治疗前、治疗24周OC、P1NP、β-CTX、25-OH-D₃比较差异均无统计学意义（均P>0.05）。3组患者治疗48周OC、25-OH-D₃比较差异均有统计学意义（均P<0.05）。LIR组治疗48周OC较治疗前升高（P<0.01）,治疗24、48周25-OH-D₃均较治疗前升高（均P<0.05）;治疗48周OAD组OC较治疗前下降（P<0.01）。与治疗24周比较,LIR组治疗48周25-OH-D₃明显升高（P<0.05）。治疗48周,与GLA组、OAD组相比,LIR组OC、25-OH-D₃均升高（均P<0.05）。3组患者治疗前后腰椎、股骨颈和髋关节BMD比较差异均无统计学意义（均P>0.05）。结论 LIR在减重的同时对BMD有保护作用,推测与其存在促进骨形成作用相关。更多还原

【Abstract】 Objective To investigate the effects of Liraglutide（LIR） and Insulin glargine（GLA） on bone metabolism in male patients with type 2 diabetes（T2DM）.Methods Ninety nine male T2DM patients with poor glycemic control by sulfonylurea secretagogues（SU） and/or α-glycosidase inhibitors（AGI） in our hospital from January to June 2018 were enrolled.Patients were randomly divided into 3 groups with 33 cases in each group:patients in the LIR group were treated with Liraglutide with SU and/or AGI;patients in the GLA group were treated with insulin glargine with SU and/or AGI,and patients in the oral antidiabetic drugs（OAD） group were treated with SU and/or AGI alone.Fasting plasma glucose（FPG）,2 h-postprandial plasma glucose（2 h-PBG）,glycosylated hemoglobin(HbA_1C),body Mass Index（BMI）,low-density lipoprotein cholesterol（LDL-C）,triglyceride（TC）,osteocalcin（OC）,Procollagen IN-Terminal Propeptide（PINP）,β-C-terminal cross-linked telopeptide（β-CTX）,and 25-OH-D₃ were measured and compared among the three groups before treatment,24 and 48 weeks after treatment.Bone mineral density（BMD）of the femoral neck,hip,and lumbar were measured by dual-energy X-ray absorptiometry at baseline and the end of the study.Results Ninety of 99 patients completed the 48-week intervention with 30 patients per group.The level of FPG,2 h-PBG,HbA_1C,and TG were significantly decreasing at 24 and 48 weeks in three groups compared to baseline values（all P<0.01）.There were statistically significant differences in 2 h-PBG,HbA_1C, BMI,and LDL-C between the three groups of patients treated for 24 weeks（all P<0.05）,but there were no statistically significant diference in FPG and TG（all P>0.05）.There were statistically significant differences in 2 h-PBG,BMI,and LDL-C between the three groups of patients treated for 48 weeks（all P<0.05）,but there were no statistically significant diference in FPG,HbA_1C, and TG（all P>0.05）.There was a statistically significant differences in LDL-C after 24 and 48 weeks of treatment in the LIR group（P<0.05）.The BMI,2 h-PBG,and LDL-C levels in the LIR group were lower than these in the GLA and OAD groups at 24 and 48 weeks of treatment（all P<0.05）.There were no statistically significant differences in OC,PINP,β-CTX,and 25-OH-D₃ between the three groups before treatment and 24 weeks after treatment（all P>0.05）.There were statistically significant differences in OC and 25-OH-D₃ between the three groups of patients treated for 48 weeks（all P<0.05）.The OC level was higher in the LIR group after 48 weeks of treatment（P<0.01）,and the level of 25-OH-D₃ in the LIR group was higher at 24 and 48 weeks than before treatment（all P<0.05）.The OC level was lower in the OAD group after48 weeks of treatment（P<0.01）.Compared with 24 weeks of treatment,the 25-OH-D₃ level in the LIR group was higher at 48 weeks of treatment（P<0.05）.Compared with the GLA group and the OAD group,the OC and 25-OH-D₃ level in the LIR group were higher at 48 weeks of treatment（all P<0.05）.The mean BMD of the femoral neck,hip,and lumbar spine（L1-4） were not changed in the LIR,GLA and OAD group from baseline to end of the study（P>0.05）.Conclusion The plasma levels of OC increased after LIR treatment for 48 weeks compared with the GLA and OAD group,although the level of HbA_1C in the three groups are comparable.BMD remained stable despite the LIR-induced weight loss.It is suggested that LIR has the effect of promoting osteogenesis with fewer and mild adverse reactions,and it can be widely applied in clinical practice.更多还原