摘要
目的 探讨特发性 1型糖尿病 (T1DM)的临床特征及其不同亚型的诊断要点。 方法 对 14 4例自发酮症起病的糖尿病患者检测谷氨酸脱羧酶抗体 (GAD Ab)、蛋白酪氨酸磷酸酶抗体(IA 2Ab)和胰岛素自身抗体 (IAA) ,根据阳性与否分为A组和B组 ,比较两组的临床特征、生化指标和HLA DQA1、DQB1易感和保护基因频率的差异。其次 ,将B组根据携带HLA DQ易感和保护基因单体型的不同分为有易感无保护 [S(+)P(- ) (B1组 ) ]、有保护无易感 [S(- )P(+) ]、两者皆无 [S(- )P(- ) ]、两者皆有 [S(+)P(+) ]4组 ,并进行比较。然后 ,将不携带HLA DQ易感基因单体型 [S(- ) ]患者根据体质指数 (BMI)分为非肥胖组 (B2组 )和肥胖组 (B3组 )。比较两组间临床特征的差异 ,并进一步将B1、B2、B3组与A组比较。 结果 B组较A组发病年龄大 ,BMI高 ,肥胖百分率高 ,更容易合并高血压 ,酮症程度较轻 ,甘油三酯、空腹和餐后C肽较高 ,2年后停用胰岛素的比例较高 ,携带HLA DQ易感基因的频率低、保护基因频率高。B1、B2、B3组与A组比较 ,A组发病年龄最轻 ,起病时酮症最严重 ,C肽水平最低 ,2年后停用胰岛素比例为 0 % ;B3组发病年龄最大 ,起病时酮症最轻 ,C肽水平最高 ,2年后停用胰岛素的比例约为 70 % ;B1、B2两组临床特征介于A组和B3组之间。?
Objective To investigate the clinical characteristics and diagnostic points of idiopathic type 1 diabetes and its subtypes. Methods Firstly, islet autoantibodies,including glutamic acid decarboxylase antibody (GAD-Ab), protein tyrosine phosphate antibody (IA2-Ab) and insulin autoantibody (IAA),were measured in 144 diabetics with an initial onset of unprovoked ketosis or ketoacidosis. The clinical characteristics, biochemical parameters and HLA-DQ genotypes were compared between patients with (group A,n=60 ) and without autoantibodies (group B, n=84 ). Secondly, according to HLA DQA1-DQB1 haplotypes,group B were further divided into four groups,including S(+)P(-) (group B1, n=16 ), S(-)P(+)(n=10), S(-)P(-)(n=28) and S(+)P(+)(n=3). S(+)P(-) were patients with susceptible HLA DQA1-DQB1 haplotypes and without protective ones. S(-)P(+) were those with protective but without susceptible haplotypes. S(-)P(-) were patients who lack the both and S(+)P(+) were those who have the both. The four groups were compared to find if there was any difference between them. Thirdly, we selected the patients whose body mass index (BMI) <25 kg/m 2 as group B2 (n=23) and those ≥25 kg/m 2 as group B3 (n=15) among patients without susceptible haplotypes [S(-)]. The clinical characteristics were compared between group B2 and group B3, to evaluate if there were any difference between group A and groups B1, B2 and B3. Results Compared with group A, patients in group B owned older age at onset, higher BMI, more obese, less severe DKA, higher level of serum triglyceride and C peptide and more often combined with hypertension. After 2-year follow-up, more patients in group B could achieve acceptable glycemic control or even discontinue insulin therapy. Lower frequency of susceptible HLA DQA1-DQB1 haplotypes and higher frequency of protective ones were found in patients in group B than those in group A. Among patients in four groups, group B1, B2, B3 and group A, patients in group A demonstrated the youngest age at onset, most severe DKA and lowest level of serum C peptide. After 2-year follow-up, no patients could discontinue insulin injection and also obtained glycemic control. On the other hand, patients in group B3 had the oldest age at onset, least severe DKA and highest level of serum C peptide. After 2-year follow-up, more than 70% patients could obtain good glycemic control without insulin. The phenotype of patients in group B2 and B3 were intermediate between group A and group B3. Conclusion There are three key points for diagnosing a patient with idiopathic type 1 diabetes:(1)New-onset (duration less than 6 months) diabetes with unprovoked ketosis or DKA. (2)Islet autoantibodies (GAD-Ab, IA2-Ab, IAA) negative. (3)Excluding diabetes with frank etiology. Idiopathic type 1 diabetes is distinct disease with heterogeneous phenotypes. HLA-DQ genotyping is recommended to determine the subtypes: (1)autoimmune-prone idiopathic type 1 diabetes, (2)typical idiopathic type 1 diabetes, and (3)atypical idiopathic type 1 diabetes. This is helpful to its prognosis judgment and etiological investigation.
基金
国家自然科学基金 ( 3 93 70 3 43 )
卫生部优秀青年科技人才基金 (Q942 0 )
湖南省卫生厅重点科研基金 ( 2 0 0 1 Z0 4)
教育部跨世纪人才基金项目 ( 2 0 0 2 48)资助
