二甲双胍联合胰岛素治疗对非肥胖成人隐匿性自身免疫糖尿病患者胰岛功能的影响  

Effect of combining metformin with insulin on β-cell function in non-obese patients with latent autoimmune diabetes in adults

作　　者：武超[1] 颜湘[1] 杨亚玲 黄干[1] 向宇飞[1] 李霞[1] 周智广[1] Wu Chao;Yan Xiang;Yang Yaling;Huang Gan;Xiang Yufei;Li Xia;Zhou Zhiguang(Department of Metabolism and Endocrinology,Second Xiangya Hospital,Central South University,Key Laboratory of Diabetes Immunology(Central South University),Ministry of Education,National Clinical Research Center for Metabolic Diseases,Changsha 410011,China;Department of Endocrinology,Shanghai Public Health Clinical Center,Shanghai 200083,China)

机构地区：[1]中南大学湘雅二医院代谢内分泌科、糖尿病免疫学教育部重点实验室、国家代谢性疾病临床医学研究中心,长沙410011 [2]上海市公共卫生临床中心内分泌科,上海200083

出　　处：《中华糖尿病杂志》2023年第9期820-827,共8页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家重点研发计划子课题(2022YFC2010102)。

摘　　要：目的探究二甲双胍对非肥胖成人隐匿性自身免疫糖尿病(LADA)患者胰岛功能的保护作用。方法为历史性队列研究。从中南大学湘雅二医院内分泌科于2008至2012年间建立的LADA队列中筛选出10例接受二甲双胍联合胰岛素治疗(500~850 mg, 2次/d)的非肥胖LADA患者(双胍组), 同时根据1∶1匹配单用胰岛素治疗的对照组。随访时间共3年, 在基线和随访期间测量两组患者的身高、体重、腰围、臀围、收缩压(SBP)、舒张压(DBP)等指标并计算体重指数(BMI)和腰臀比(WHR), 检测糖化血红蛋白(HbA1c)、空腹血糖、餐后1 h血糖、餐后2 h血糖、血脂。进行混合膳食耐量试验并检测血清空腹C肽(FCP)、餐后1 h C肽(1hCP)、餐后2 h C肽(2hCP)、峰值C肽(CP_(max))、C肽变化量(ΔCP)和C肽曲线下面积(AUCC)以评估胰岛功能。同时每次随访均记录患者的胰岛素用法及用量, 并计算患者每日每千克胰岛素用量。通过重复测量数据协方差分析比较随访期间两组之间代谢指标及胰岛功能的差异。结果在3年随访期间, 双胍组在36个月时SBP较基线有所升高[分别为(123±6)和(114±11)mmHg(1 mmHg=0.133 kPa), P=0.043], 两组BMI、腰围、WHR、血糖、血脂等代谢指标及胰岛素用量较基线差异均无统计学意义(P>0.05), 上述指标组间比较差异亦无统计学意义(P>0.05)。对照组在6个月即出现1hCP较基线显著降低[分别为(462.1±378.9)和(923.6±895.7)pmol/L, P=0.039], 胰岛功能随着随访时间显著衰减。而双胍组到随访24个月时才观测到FCP较基线有显著差异[分别为(296.0±264.2)和(463.9±304.3)pmol/L, P=0.017], 随访终点时双胍组各胰岛功能评价指标较基线均出现显著下降(P<0.05)。随访12个月时双胍组胰岛功能显著高于对照组(P<0.05), 然而到随访24及36个月时, 两组间C肽比较差异均无统计学意义(P>0.05)。结论本小样本回顾性研究提示二甲双胍与胰岛素联合使用可能有助�Objective To investigate the effect of metformin plus insulin onβ-cell function in non-obese patients with latent autoimmune diabetes in adults(LADA).Methods A LADA cohort established between 2008 and 2012 was studied retrospectively.Ten non-obese patients with LADA treated with insulin plus metformin(500-850 mg,twice daily)were screened from the cohort and matched 1∶1 with the insulin-treated control group.The retrospective cohort was followed up for a total of 3 years.Height,weight,waist and hip circumference,systolic blood pressure(SBP)and diastolic blood pressure(DBP)were measured,and body mass index(BMI)and waist-hip ratio(WHR)were calculated.Glycated hemoglobin A_(1c)(HbA_(1c)),fasting plasma glucose,1 h postprandial plasma glucose,2 h postprandial plasma glucose,blood lipids were measured at baseline and during follow-up.A mixed meal tolerance test was performed and C-peptide was measured.β-cell function was evaluated with fasting C-peptide(FCP),1 h postprandial C-peptide(1hCP),2 h postprandial C-peptide(2hCP),peak C-peptide(CP_(max)),variation in C-peptide(ΔCP)and area under the curve of C-peptide(AUCC).Insulin regimen and insulin dose were documented at each visit,and total daily insulin dose per kg was calculated.Differences in metabolic profiles andβ-cell function during follow-up between the two groups were analyzed by repeated-measures analysis of covariance.ResultsAt the end of the three-year follow-up,the metformin group had an increase in SBP compared with baseline[(123±6)vs.(114±11)mmHg(1 mmHg=0.133 kPa),P=0.043],and there were no significant differences in BMI,waist circumference,WHR,blood glucose,blood lipids and other metabolic profiles,or insulin dose between the two groups compared with the baseline,nor were there any significant difference between the two groups at any time point(all P>0.05).1hCP in the control group was significantly reduced from baseline[(462.1±378.9)vs.(923.6±895.7)pmol/L,P=0.039]at the 6th month,with a significant decline in islet function at follow-ups.Notabl

关 键 词：糖尿病 成人隐匿性自身免疫糖尿病 二甲双胍 胰岛Β细胞功能 

分 类 号：R587.1[医药卫生—内分泌]