1型糖尿病起病过程的临床异质性分析

目的 了解1型糖尿病起病过程的临床异质性.方法 回顾性分析自1999年1月至2009年12月广州中山大学附属第一医院内分泌科205例新诊断1型糖尿病患者的临床资料.根据症状出现至就诊时间,将患者分为暴发性1型糖尿病（FT1DM）、急性起病及缓慢起病的1型糖尿病（出现症状至就诊时间分别≤或＞3个月）,比较3组患者临床特点及实验室检查资料.血清谷氨酸脱羧酶抗体（GADA）、胰岛细胞自身抗体（ICA）、胰岛素自身抗体（IAA）均为定性检测,GADA采用酶联免疫吸附法（ELISA）,ICA、IAA及血清C肽检测采用放射免疫法.计量资料采用单因素方差分析或两个独立样本的t检验,计数资料采用多变量卡方检验及Fisher精确概率法进行统计分析.结果 FT1DM、急性起病及缓慢起病的1型糖尿病分别占8.8%、66.8%及24.4%.3组中FT1DM患者血糖升高更明显[分别为（31±12）、（25±10）、（24±8）mmol/L,F=4.462,P＜0.05],而糖化血红蛋白略高于正常[分别为（6.8±1.1）%、（12.3±2.4）%、（13.9±2.7）%,F=54.661,P＜0.05],酮症酸中毒更常见（分别为93.8%、45.3%、8.0%,F=44.943,P=0.000）,合并低钠血症、高钾血症、酸中毒、肝肾功能受损更严重,合并妊娠的比例更高（分别为22.2%、0、0,X2=20.982,P=0.000）.缓慢起病的1型糖尿病患者起病年龄及体质指数较另两组大,而体质量下降更明显,负荷后C肽水平明显高于另外两组[分别为（0.40±0.36）、（0.10±0.13）、（0.34±0.26）nmol/L,F=8.752,P＜0.05].儿童及青少年在急性起病的1型糖尿病中所占比例更高,其临床表型与成人相似.结论3组患者起病过程的临床异质性十分明显,提示1型糖尿病可能存在不同的疾病触发机制.

Clinical heterogeneity of type 1 diabetes mellitus at onset

Objective To investigate the clinical heterogeneity of type 1 diabetes mellitus (T1 DM) at onset.Method A total of 205 newly diagnosed T1 DM patients discharged from the hospital between January 1999 and December 2009 were retrospectively reviewed.Clinical characteristics and laboratory data at onset were compared among fulminant type 1 diabetes ( FT1 DM ) and those with duration of symptoms before diagnosis shorter (acute-onset) or longer (slow-onset) than 3 months.Antibodies to glutamic acid decarboxylase (GADA) were determined by enzyme-linked immunosorbent assay (ELISA), while islet cell antibodies (ICA) ,insulin autoantibody(IAA) and serum C-peptide were detected using radioimmunoassay (RIA).Statistical analyses were performed using One-way ANOVA and two independent samples t-test for measurement data, multivariate Chi-square and Fisher's exact probability test were used for enumeration data.Results The proportions of FT1 DM, acute-onset and slow-onset T1 DM were 8.8%, 66.8%, 24.4% respectively.The onset of FT1 DM was so abrupt that the concentration of plasma glucose was prominently elevated ((31±12) vs (25 ±10), (24 ±8) mmol/L, F=4.462, P＜0.05), whereas HbA1c was disproportionately near normal ( (6.8±1.1 ) % vs ( 12.3 ± 2.4 ) %, ( 13.9 t 2.7 ) %, F = 54.661, P ＜0.05).Ketoacidosis was almost inevitable at diagnosis ( 93.8% vs 45.3%, 8.0%, F = 44.943, P =0.000) and the accompanied metabolic derangement.Hyponatremia, hyperkalemia, acidosis, association with liver and kidney dysfunction was more severe in FT1 DM group.Association with pregnancy was more frequent as compared to the other 2 groups ( 22.2% vs 0, 0, X2 = 20.982, P = 0.000).Patients with slowonset type were relatively older and had greater BMI but lost more weight at diagnosis.The post-load C-peptides were relatively higher( (0.40 ±0.36) vs (0.10 ±0.13), (0.34 ±0.26) nmol/L, F=8.752,P ＜ 0.05 ) in this group.Children and adolescents constituted a greater proportion in the acute-onset T1DM group, and the clinical characteristics were similar to the adult-onset counterpart.Conclusions Clinical heterogeneity in the 3 groups is apparent, which might indicate different mechanisms that trigger the development of T1DM leading to the phenotypic discrepancy.