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自身抗体针对锌转运体 8 与新诊断为自身免疫性糖尿病患者的年龄和代谢状态有关。

Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes.

机构信息

Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, Szpitalna Street 27/33, 60-572, Poznan, Poland.

Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza Street 2, 60-101, Poznan, Poland.

出版信息

Acta Diabetol. 2018 Mar;55(3):287-294. doi: 10.1007/s00592-017-1091-x. Epub 2018 Jan 11.

Abstract

AIMS

To assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset.

METHODS

The study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO < 15 mmol/l, presence of ketone bodies in the blood and urine.

RESULTS

The autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (R - 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0-5.94), p = 0.04].

CONCLUSIONS

Children are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.

摘要

目的

评估 ZnT8-ab 的流行率及其与 T1DM 发病的儿童和成人其他自身抗体标志物和糖尿病酮症酸中毒发生的相关性。

方法

该研究纳入了 367 例(218 例儿童;149 例成人)T1DM 发病患者。在开始胰岛素治疗前,检测了 GAD-ab、IA2-ab、ZnT8-ab 等与糖尿病相关的自身抗体。糖尿病酮症酸中毒的定义为血糖浓度>13.9mmol/l、pH<7.30、HCO<15mmol/l、血液和尿液中存在酮体。

结果

两组研究对象的自身抗体模式不同。儿童多为两种(37.8%)和三种(49.5%)自身抗体阳性,而成人为一种(32.2%)和两种(30.7%)自身抗体阳性。青少年最常检测到的自身抗体是 ZnT8-ab(81.1%)和 IA2-ab(80.7%),而成人则是 GAD-ab(74.8%)。儿童的 ZnT8-ab(p<0.0001)滴度明显更高,但成人的 GAD-ab(p<0.0001)和 IA2-ab(p<0.0001)滴度更高。儿童更常发生糖尿病酮症酸中毒(28.4%比 10.7%,p=0.0002)。ZnT8-ab(p=0.002)和 IA2-ab(p=0.008)在酸中毒患者中报告得更多。观察到阳性抗体数量与酸中毒严重程度之间存在相关性(R=-0.129,p=0.014)。ZnT8-ab 与糖尿病酮症酸中毒的风险增加独立相关,与性别、年龄组和自身抗体数量无关[OR=2.44(95%CI 1.0-5.94),p=0.04]。

结论

儿童在诊断糖尿病时更易发生酮症酸中毒。ZnT8-ab 和 IA2-ab 在儿童中常见,而成人则常具有更高的 GAD-ab 滴度。ZnT8-ab 与更急性的糖尿病发病相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71b/5829102/3bd3e1ae6a9b/592_2017_1091_Fig1_HTML.jpg

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