DataSheet_1_The Prevalence of Islet Autoantibodies in Children and Adolescents With Type 1 Diabetes Mellitus: A Global Scoping Review.docx

Background and PurposePancreatic islet autoantibodies (iAb) are the hallmark of autoimmunity in type 1 diabetes. A more comprehensive understanding of the global iAb prevalence could help reduce avertible morbidity and mortality among children and adolescents and contribute to the understanding in the observed differences in the incidence, prevalence and health outcomes of children and adolescents with type 1 diabetes across and within countries. We present the first scoping review that provides a global synthesis of the prevalence of iAb in children and adolescents with type 1 diabetes.
Research Design and MethodsWe searched Ovid MEDLINE® with Daily Update, Embase (Elsevier, embase.com) and PubMed (National Library of Medicine -NCBI), for studies pertaining to prevalence in children and adolescents (0-19) with type 1 diabetes published between 1 Jan 1990 and 18 June 2021. Results were synthesized using Covidence systematic review software and meta-analysis was completed using R v3·6·1. Two reviewers independently screened abstracts with a third reviewer resolving conflicts (k= 0·92).
ResultsThe review revealed 125 studies from 48 different countries, with 92 from high-income countries. Globally, in new-onset type 1 diabetes, IA-2A was the most prevalent iAb 0·714 [95% CI (0·71, 0·72)], followed by ICA 0·681 [95% CI (0·67, 0·69)], ZnT8A was 0·654 [95% CI (0·64, 0·66)], GADA 0·636 [95% CI (0·63, 0·66)] and then IAA 0·424 [95% CI (0·42, 0·43)], with substantial variation across world regions. The weighted mean prevalence of IA-2A was more variable, highest in Europe at 0·749 [95% CI (0·74, 0·76)] followed by Northern America 0·662 [95% CI (0·64, 0·69)], Latin America and the Caribbean 0·632 [95% CI (0·54, 0·72)], Oceania 0·603 [95% CI (0·54, 0·67)], Asia 0·466 [95% CI (0·44, 0·50)] and Africa 0·311 [95% CI (0·23, 0·40)]. In established cases of type 1 diabetes, GADA was the most prevalent iAb 0·407 [95% CI (0·39, 0·42)] followed by ZnT8A 0·322 [95% CI (0·29, 0·36)], IA-2A 0·302 [95% CI (0·29, 0·32)], IAA 0·258 [95% CI (0·24, 0·26)] and ICA 0·145 [95% CI (0·13, 0·16)], again with substantial variation across world regions.
ConclusionUnderstanding the global prevalence of iAb in children and adolescents with type 1 diabetes could help with earlier identification of those at-risk of developing type 1 diabetes and inform clinical practice, health policies, resource allocation, and targeted healthcare interventions to better screen, diagnose and manage children and adolescents with type 1 diabetes

背景与研究目的：胰腺胰岛自身抗体（pancreatic islet autoantibodies，iAb）是1型糖尿病自身免疫的标志性特征。对全球胰岛自身抗体患病率的更全面认识，有助于降低儿童及青少年群体中可避免的发病率与死亡率，同时有助于解析不同国家及国家内部1型糖尿病儿童青少年的发病率、患病率及健康结局所存在的差异。本研究开展了首项范围综述（scoping review），对儿童及青少年1型糖尿病患者的胰岛自身抗体患病率进行全球整合分析。

研究设计与方法：本研究检索了每日更新版Ovid MEDLINE®、Embase（爱思唯尔，embase.com）以及PubMed（美国国立医学图书馆-NCBI）数据库，筛选1990年1月1日至2021年6月18日期间发表的、针对0-19岁儿童及青少年1型糖尿病患者患病率的相关研究。研究结果通过Covidence系统综述软件进行整合，并采用R v3·6·1软件完成荟萃分析。由2名研究者独立筛选文献摘要，第三名研究者对分歧进行仲裁（Kappa值=0.92）。

研究结果：本次综述共纳入来自48个国家的125项研究，其中92项来自高收入国家。全球范围内，新发1型糖尿病患者中，胰岛抗原2抗体（IA-2A）为最常见的胰岛自身抗体，患病率为0.714 [95%置信区间(0.71, 0.72)]，其次为胰岛细胞抗体（ICA）0.681 [95%置信区间(0.67, 0.69)]、锌转运体8抗体（ZnT8A）0.654 [95%置信区间(0.64, 0.66)]、谷氨酸脱羧酶抗体（GADA）0.636 [95%置信区间(0.63, 0.66)]，最后为胰岛素自身抗体（IAA）0.424 [95%置信区间(0.42, 0.43)]，且各抗体患病率在全球不同区域存在显著差异。胰岛抗原2抗体（IA-2A）的加权平均患病率波动更为显著：欧洲最高，为0.749 [95%置信区间(0.74, 0.76)]，其次为北美0.662 [95%置信区间(0.64, 0.69)]、拉丁美洲及加勒比地区0.632 [95%置信区间(0.54, 0.72)]、大洋洲0.603 [95%置信区间(0.54, 0.67)]、亚洲0.466 [95%置信区间(0.44, 0.50)]，非洲为0.311 [95%置信区间(0.23, 0.40)]。对于已确诊的1型糖尿病患者，谷氨酸脱羧酶抗体（GADA）为最常见的胰岛自身抗体，患病率为0.407 [95%置信区间(0.39, 0.42)]，其次为锌转运体8抗体（ZnT8A）0.322 [95%置信区间(0.29, 0.36)]、胰岛抗原2抗体（IA-2A）0.302 [95%置信区间(0.29, 0.32)]、胰岛素自身抗体（IAA）0.258 [95%置信区间(0.24, 0.26)]以及胰岛细胞抗体（ICA）0.145 [95%置信区间(0.13, 0.16)]，且不同区域的患病率仍存在显著差异。

研究结论：明晰儿童及青少年1型糖尿病患者的全球胰岛自身抗体（iAb）患病率，有助于更早识别1型糖尿病发病风险人群，同时可为临床实践、卫生政策制定、资源配置以及针对性医疗干预提供依据，从而更好地开展1型糖尿病儿童青少年的筛查、诊断与管理工作。