成人隐匿性自身免疫性糖尿病患者胰岛β细胞功能的6年前瞻性研究

Six-years follow-up of beta-cell function in patietns with latent autoimmune diabetes in adults (LADA)

目的 探讨谷氨酸脱羧酶抗体 (GAD Ab)阳性的成人隐匿性自身免疫性糖尿病(LADA)患者胰岛 β细胞功能变化的特点及其影响因素。 方法 GAD Ab阳性的LADA患者 4 5例(LADA 1组 16例 ,LADA2组 2 9例 ) ,年龄 2 8～ 6 8岁 ;GAD Ab阴性的 2型糖尿病 (T2DM )患者 4 5例(T2DM 1组 16例 ,T2DM 2组 2 9例 ) ,年龄 2 6～ 6 8岁。每半年随访一次 ,LADA 1组和T2DM 1组随访至第 6年 ,LADA 2组和T2DM 2组随访至第 1 5年。测定空腹C肽 (FC P)和 10 0g馒头餐后 2hC肽 (2hC P)及糖代谢控制指标。采用放射配体法测定GAD Ab ,放免法测定C P。 结果 LADA1组的FC P较入组时下降 5 0 %以上 ,随访第 1 5年时为 2 5 % ,随访第 2 5年平均水平呈显著性下降[(396± 189) pmol/L对 (5 73± 2 89) pmol/L ,P <0 0 5 ]直至第 6年 ,而T2DM 1组的FC P在随访期间则无显著变化 (P >0 0 5 ) ;LADA患者平均每年FC P下降 15 8% (4 0 %～ 91 0 % ) ,而T2DM平均为 5 2 % (- 3 5 %～ 35 5 % ,P =0 0 0 0 )。LADA患者的FC P与GAD Ab滴度呈负相关 (r =-0 4 83,P =0 0 0 0 ) ;FC P平均每年下降百分数的相关因素为GAD Ab滴度、体质指数 (BMI)和发病年龄 (r分别为 0 4 0 8、- 0 30 1和 - 0 5 2 3,P <0 0 5 )。 结论 LADA患者胰岛 ?

Objective To investigate the characteristics of t he changes of islet β cell function in LADA patients with glutamic acid decarbo xylase antibody (GAD-Ab) positivity, and explore the prognostic factors for β cell function. Methods Forty-five LADA patients with GAD-A b positivity screened from T2DM patients included 16 LADA1 and 29 LADA2, aged fr om 28 to 68yr. Forty-five T2DM patients without GAD-Ab positivity included 16 T2DM1 and T2DM2, aged from 26～68yr. They were followed once every half a year . LADA1 and T2DM1 groups were followed up to the 6th year, while the LADA2 and T2DM2 groups were followed for 1.5 years up to now. Fasting and postprandial C -peptides (FCP and PCP), blood glucose and glycated hemoglobin were measured. GAD-Ab was determined by radioligand assay and C-peptide by RIA. Res ults The percentage of patients whose FCP decreased more than 50% when compared with the baseline reached to 25.0% at 1.5th year in LADA1 group, and decreased FCP level (396±189 vs 573±289 pmol/L, P<0.05) was found at 2.5 th year and continued to the end of follow-up. No changes of the above pa rameters in T2DM1 patients were found (P>0.05). The decreased average perc entages of FCP per year in LADA and T2DM patients were 15.8% (4.0%～91.0%) an d 5.2% (-3.5%～35.5%, P=0.000) respectively. The index of GAD-Ab was ne g atively correlated with the fasting C-peptide in LADA patients (r=-0.483, P= 0.000). The decreased percentage of FCP per year in LADA patients were corre lated with GAD-Ab index, BMI and age at onset (r=0.408, -0.301 and -0.52 3 respectively, P< 0.05). Conclusions The decreasing rate of islet β cell function in LADA, being much heterogeneous, was 3 times m ore than that of T2DM patients. The titer of GAD-Ab was an important predictor for the change of islet β cell function, and age at onset and BMI could also a ct as the predictors.