起病年龄对1型糖尿病患者蜜月期发生情况及胰岛功能的影响

Effect of onset age on honeymoon period occurrence and islet function in type 1 diabetes mellitus

目的探讨各年龄阶段1型糖尿病(T1DM)患者发生蜜月期的情况,以及蜜月期对各年龄阶段起病患者胰岛功能影响的差异。方法回顾性分析2010年5月至2018年10月在中南大学湘雅二医院T1DM综合管理门诊规律随访就诊的305例新发T1DM患者。将不同起病年龄患者分为儿童起病组(0~11岁,118例)、青少年起病组(12~18岁,71例)和成人起病组(>18岁,116例)。分析T1DM患者基线和随访过程中收集到的临床资料和各项检测指标,以每3个月随访过程中,混合餐耐受试验出现任一点C肽>300 pmol/L或胰岛素剂量校正的糖化血红蛋白指数≤9判断蜜月期起止时间,起病12个月内一直未达到蜜月期标准的患者定义为无蜜月期。蜜月期持续时间比较采用Kaplan-Meier、Log-rank法进行生存分析,起病4年内重复测量的随访C肽数据采用广义估计方程分析。结果305例T1DM患者中共有202例出现蜜月期,蜜月期发生率为66.2%。青少年起病组、儿童起病组和成人起病组中的蜜月期发生率逐渐降低,分别为87.3%(62/71)、61.0%(72/118)和58.6%(68/116),差异有统计学意义(P<0.05),但组内比较儿童起病组与成年起病组患者间的发生率差异无统计学意义(P=0.709)。儿童起病组、青少年起病组和成年起病组的蜜月期持续时间分别为7.1(5.1,13.2)、13.6(7.3,23.4)和10.3(6.5,16.9)个月,差异有统计学意义(P<0.05)。随访4年内C肽分析显示,无蜜月期患者中,成人起病组2 h C肽低于儿童起病组(P=0.029),空腹C肽两组差异无统计意义(P=0.520);而在有蜜月期患者中,成人起病组空腹C肽和2 h C肽均明显高于儿童起病组(P值分别为0.018和0.002)。结论青少年起病患者蜜月期发生率比成年和儿童起病患者更高,儿童起病患者蜜月期持续时间更短。蜜月期是成年起病患者保留胰岛功能的有利因素。

Objective To investigate the occurrence of honeymoon period and its influence on long-term islet function in type 1 diabetes mellitus(T1DM)with different onset ages.Methods A retrospective analysis was performed on 305 newly diagnosed T1DM patients who were regularly followed up in the T1DM General Management Clinic of the Second Xiangya Hospital of Central South University from May 2010 to October 2018.According to the age of onset,patients were divided into the child-onset group(1 to 11 years old,118 cases),adolescent-onset group(12 to 18 years old,71 cases),or adult-onset group(>18 years old,116 cases).Clinical data and indicators collected during baseline and follow-up of T1DM patients were analyzed.The starting and ending time of the honeymoon period was determined according to the C-peptide level>300 pmol/L or the insulin dose-adjusted glycosylated hemoglobin≤9 at any point during every 3 months of follow-up.Those who did not meet these criteria within 12 months of onset were defined as having no honeymoon.The duration of the honeymoon period was compared by Kaplan-Meier and Log-rank methods for survival analysis.The follow-up C-peptide data repeated measurements within 4 years of the onset of disease were analyzed by generalized estimation equation.Results In the all T1DM patients(n=305),202 had honeymoon,and the incidence rate of honeymoon was 66.2%.The occurrence of honeymoon decreased gradually in the adolescent-onset group,child-onset group,and adult-onset group,which were 87.3%(62/71),61.0%(72/118),and 58.6%(68/116),respectively,with statistical significance(P<0.05).However,there was no statistical significance in the incidence of child-onset group compared with adult-onset group(P=0.709).The duration of honeymoon was 7.1(5.1,13.2),13.6(7.3,23.4)and 10.3(6.5,16.9)months in the child-onset group,adolescent-onset group and adult-onset group,respectively(P<0.05).The C-peptide analysis in the follow-up period of 4 years showed that,among the patients without honeymoon,the 2-hour C-peptide in the adult-onset group was lower than that in the child-onset group(P=0.029),and there was no significant difference in fasting C-peptide between the two groups;while in patients who experienced honeymoon,the fasting and 2-hour C-peptide in the adult-onset group were significantly higher than those in the child-onset group(P=0.018 and 0.002,respectively).Conclusions Compared with children and adult-onset type 1 diabetes patients,adolescent-onset patients have a higher proportion of honeymoon,and child-onset patients have a shorter honeymoon duration.Honeymoon occurrence is a favorable factor for adult-onset patients to preserve islet function.