ABC分型法对急性起病1型糖尿病亚型诊断的研究

Use of ABC typing to redefine subtypes of acute-onset type 1 diabetes mellitus： study of 308 patients

目的探讨ABC分型法对急性起病1型糖尿病亚型诊断的可行性及其诊断界值。方法用放射配体法检测308例急性起病1型糖尿病患者谷氨酸脱羧酶抗体（GAD—Ab）和酪氨酸磷酸酶抗体（IA-2A），根据抗体阳性与否分为A＋组（任一抗体阳性）和A-组（抗体皆为阴性）。比较A＋和A-组临床特征、胰岛功能变化及HLA—DQ易感基因型的差异，判断胰岛自身抗体对急性起病1型糖尿病分型诊断的价值。进一步以随访2年时胰岛素用量作为标准（〈20U／d或≥20U／d），通过绘制ROC曲线来判断在A＋和A-患者中，用空腹C肽、体质指数和HLA—DQ基因型进一步分型的可能性和最佳诊断截点。分析ABC分型法各亚型患者的临床特点。结果胰岛自身抗体可将急性起病1型糖尿病分为临床特征完全不同的A＋和A-两组，是分型诊断的首选指标。空腹C肽在A＋和A-两组患者中均可进一步分型，A＋患者的最佳诊断截点为150pmol／L，而A-患者为250pmol／L。体质指数在A-患者中可进一步分型诊断，最佳截点为24kg／m^2，而在A十患者中无此作用。HLA—DQ易感基因型在A＋和A-两组患者中均无进一步分型诊断的价值。结论ABC分型法可对急性起病的1型糖尿病患者进行亚型诊断，有助于判断预后。

Objective To investigate the feasibility of ABC typing to redefine the subtypes of acuteonset type 1 diabetes meUitus （DM）. Methods Radioligand assay was used to detect glutamic acid decarboxylase-antibedy （GAD-Ab） and tyrosine phosphatase autoantibedy （IA-2A） in 308 patients with acute-onset type 1 DM. The patients were thus divided into 2 groups： pancreatic islet auto-antibedy （demonstrated as A） positive group---positive in GAD-Ab or IA-2A--and pancreatic islet auto-antibedy negative group. The clinical features and frequencies of HLA-DQ genotypes of these groups were compared. Within 24 hours after the correction of diabetic ketosis or diabetic ketoacidosis and after fasting for at least 8 h fasting and postprandial venous blood samples were collected to detect the fasting C peptide （ FCP, demonstrated as B） reflecting the beta cell function, and postprandial C peptide （PCP）. The patients were followed up for 2 years to know the insulin dosage （ 〈 20 U/d or ≥ 20 U/d）. Receiver operating characteristic curve （ROC） was drawn to judge the values of fasting C peptide, body mass index （ BMI, demonstrated as C） reflecting the central obesity, and HLA-DQ genotype in further typing among the A ＋ and A - patients and the optimal cutoff points thereof. Results Compared with the A - group, the metabolic disorders at the onset were more severe, the insulin dosage at the 2-year follow-up was higher, and the percentage of susceptible HLA-DQ genotypo was higher in the A ＋ group （P 〈 0.05 or 〈 0.01 ）. The level of FCP （B） could be used to further subtyping in both A ＋ and A - groups, with the optimal cutoff point of 150 pmol/L in the A ＋ group and with the optimal cutoff point of 250 pmol/L in the A - group. BMI could be used for further classification in only A - group with the optimal cutoff point of 24 kg/m^2.HLA-DQ genotypes were of little value in further classification both in A ＋ and A - groups. Conclusion ABC typing may be used as a new way to redefine the subtypes in acute-onset type 1 DM for prognosis.