高谷氨酸脱羧酶自身抗体（GADA）滴度增加成人隐匿性自身免疫性糖尿病（LADA）患者胰岛素治疗需求风险：一项7年随访研究（NIRAD研究7）
High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).
作者信息
Zampetti Simona, Campagna Giuseppe, Tiberti Claudio, Songini Marco, Arpi Maria Luisa, De Simone Giuseppina, Cossu Efisio, Cocco Lorenzo, Osborn John, Bosi Emanuele, Giorgino Francesco, Spoletini Marialuisa, Buzzetti Raffaella
机构信息
Department of Experimental Medicine'Sapienza' University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Internal MedicineS. Michele Hospital, Cagliari, ItalyEndocrinologyGaribaldi di Nesima Hospital, Catania University, Catania, ItalyDiabetologic CenterDistretto 54 ASL Napoli 3, Naples, ItalyEndocrinology and DiabetesDepartment of Medical Sciences, University of Cagliari, Cagliari, ItalyU.O.C. Diabetologia/Endocrinology'A. Cardarelli' Hospital, Campobasso, ItalyDepartment of Public Health Sciences and Infectious Diseases'Sapienza' University of Rome, Rome, ItalySan Raffaele Scientific InstituteDiabetes Research Institute, Milan, ItalySection of Internal MedicineEndocrinology, Andrology and Metabolic Disease, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Bari, Italy.
Department of Experimental Medicine'Sapienza' University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Internal MedicineS. Michele Hospital, Cagliari, ItalyEndocrinologyGaribaldi di Nesima Hospital, Catania University, Catania, ItalyDiabetologic CenterDistretto 54 ASL Napoli 3, Naples, ItalyEndocrinology and DiabetesDepartment of Medical Sciences, University of Cagliari, Cagliari, ItalyU.O.C. Diabetologia/Endocrinology'A. Cardarelli' Hospital, Campobasso, ItalyDepartment of Public Health Sciences and Infectious Diseases'Sapienza' University of Rome, Rome, ItalySan Raffaele Scientific InstituteDiabetes Research Institute, Milan, ItalySection of Internal MedicineEndocrinology, Andrology and Metabolic Disease, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Bari, Italy
出版信息
Eur J Endocrinol. 2014 Dec;171(6):697-704. doi: 10.1530/EJE-14-0342. Epub 2014 Sep 11.
OBJECTIVE
The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up.
METHODS
This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression.
RESULTS
During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95).
CONCLUSIONS
High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.
目的
本研究旨在确定谷氨酸脱羧酶抗体（GADA）滴度及其他临床参数是否能够界定成年隐匿性自身免疫性糖尿病（LADA）患者在7年随访期间进展为胰岛素治疗的风险。
方法
本研究纳入了220例LADA患者和430例2型糖尿病患者，从GADA筛查时开始进行7年随访，以评估其向胰岛素治疗的进展情况。采用Kaplan-Meier曲线和多因素逻辑回归分析来确定能够影响这一进展的标志物。
结果
随访期间，两组的失访率均为4%。在212例LADA患者中，共有119例（56.1%）在7年随访期间需要胰岛素治疗。Kaplan-Meier曲线显示，高GADA滴度组中74/104例（71.1%）需要胰岛素治疗，而低GADA滴度组为45/108例（41.6%），2型糖尿病组为86/412例（20.9%）（两者P均<0.0001）。BMI≤25 kg/m²以及胰岛抗原2（IA-2）胞内区（IA-2IC）和锌转运体8（ZnT8）阳性也被证明是进展更快的标志物（两者P均<0.0001）。与接受饮食和/或胰岛素增敏剂治疗的患者相比，在诊断后的第一年同时接受磺脲类药物治疗的患者中，需要胰岛素治疗的LADA患者比例显著更高（P<0.001）。多因素分析证实，高GADA滴度的存在是胰岛素需求的显著预测因素（P<0.0001，OR=6.95）。
结论
高GADA滴度、BMI≤25、ZnT8和IA-2IC阳性以及在诊断后的第一年接受磺脲类药物治疗，均显著增加LADA患者进展为需要胰岛素治疗的风险。
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