羧基肽酶-H抗体与LADA患者胰岛β细胞功能关系的横断面研究

目的：探讨羧基肽酶-H自身抗体（CPH—Ab）与成人隐匿性自身免疫性糖尿病（LADA）患者胰岛β细胞功能的关系，以进一步明确其对LADA的诊断价值。方法：选择临床初诊2型糖尿病（T2DM）患者545例，采用放射配体法检测血清CPH—Ab和谷氨酸脱羧酶抗体（GAD-Ab）滴度，以筛出的CPH-Ab阳性患者为病例组，以GAD—Ab阳性患者和抗体阴性的T2DM患者为对照组，比较3组研究对象的胰岛β细胞功能（以空腹和餐后2hC肽值表示），分析CPH-Ab与成人隐匿性自身免疫性糖尿病（LADA）患者胰岛β细胞功能的关系。结果：CPH—Ab阳性患者的空腹C肽介于GAD-Ab阳性与两种抗体（GAD-Ab和CPH—Ab）均阴性的T2DM患者之间（P〈0.05），以病程分层后三者的C肽值仍具有统计学意义（均P〈0．05），而以BMI分层无明显差异（均P〉0．05）。经以年龄、起病年龄、病程、性别等为协变量校正后，3组间的空腹C肽和餐后2hC肽值仍存在显著性差异（均P〈0，001），其中CPH—Ab^＋组仅空腹C肽低于Ab—T2DM组（P〈0，05），而GAD—Ab^＋组空腹和餐后2hC肽均低于Ab^-T2DM组（P〈0．05和P〈0．01）。胰岛素缺乏患者在CPH-Ab^＋组、GAD-Ab^＋组和Ab—T2DM组的比例分别为27．6％（8／29），48．1％（8／52）和13．5％（54／400），三者间差异有统计学意义（P〈0.001）。多元线性逐步回归分析提示，GAD-Ab，BMI和空腹血糖对T2DM患者的空腹C肽和餐后2hC肽均有影响（均P〈0．05），而CPH-Ab与二者均无统计学相关（均P〉0．05）。结论：CPH抗体对LADA患者胰岛β细胞功能的影响不如GAD-Ab显著，CPH-Ab对LADA患者胰岛功能衰减的作用需前瞻性研究。

<FONT face=

OBJECTIVE: To explore the relation between carboxypeptidase-H antibody (CPH-Ab) and islet beta cell function in patients with latent autoimmune diabetes in adults (LADA) and to further confirm the diagnostic value of CPH-Ab for LADA. METHODS: Five hundred and forty-five patients who were initially diagnosed as Type 2 diabetes mellitus (T2DM) were tested with CPH-Ab and GAD-Ab by radioligand assay (RLA). T2DM patients, according to CPH-Ab and GAD-Ab status, were divided into CPH-Ab(+) group, GAD-Ab(+) group, and Ab(-) group to compare their islet beta cell function represented by fasting C-peptide (FCP) and 2h postprandial C-peptide (2hCP)]. The relation between CPH-Ab and islet beta cell function in LADA was analyzed. RESULTS: The fasting C-peptide level in CPH-Ab(+) patients was between that of GAD-Ab(+) patients and that of Ab(-) patients (P<0.05), and the difference was still significant when the 3 groups were stratified with duration of disease (All P<0.05), but not with body mess index (all P>0.05). Corrected by concomitant variables including age, age at onset, duration of disease, and sex, the differences among the 3 groups were statistically significant (both P<0.001). Among the 3 groups FCP was lower than Ab(-) group in CPH-Ab(+) (P<0.05) and both FCP and PCP were lower than Ab(-) group in GAD-Ab(+) group (P<0.05 and P<0.01). The proportions of patients with insulin deficiency in CPH-Ab(+), GAD-Ab(+), and Ab(-) group were 27.6% (8/29), 48.1% (8/52) and 13.5% (54/400), respectively, which were significantly different among the 3 groups (P<0.001). GAD-Ab, BMI, and fasting blood glucose had effects on FCP and PCP in T2DM patients (All P<0.05), while CPH-Ab did not enter the equation in multivariable stepwise regressive analysis (P>0.05). CONCLUSION: The effect of CPH-Ab is less marked than that of GAD-Ab on islet beta-cell function in LADA patients. The value of CPH-Ab for the failure of islet beta-cell function in LADA should be determined prospectively.