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芬兰儿童中的 SARS-CoV-2 和 1 型糖尿病:一项观察性研究。

SARS-CoV-2 and type 1 diabetes in children in Finland: an observational study.

机构信息

Pediatric Research Center, New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Pediatric Research Center, New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

出版信息

Lancet Diabetes Endocrinol. 2023 Apr;11(4):251-260. doi: 10.1016/S2213-8587(23)00041-4.

Abstract

BACKGROUND

Some epidemiological studies have suggested an increase in incidence of type 1 diabetes during the COVID-19 pandemic, however the mechanism(s) behind such an increase have yet to be identified. In this study we aimed to evaluate the possible role of the SARS-CoV-2 virus in the reported increase in the rate of type 1 diabetes.

METHODS

In this observational cohort study using data from the Finnish Pediatric Diabetes Register (FPDR), we assessed the incidence of type 1 diabetes (number of children with newly diagnosed type 1 diabetes per 100 000 person-years during the pandemic and the reference period) during the first 18 months of the COVID-19 pandemic in children in Finland younger than 15 years old compared with a reference period which included three corresponding pre-pandemic periods also obtained from the FPDR. Children with confirmed monogenic diabetes were excluded. We also compared the phenotype and HLA genotype of the disease between these two cohorts, and analysed the proportion of newly diagnosed people with type 1 diabetes testing positive for SARS-CoV-2 antibodies.

FINDINGS

785 children and adolescents in Finland were diagnosed with type 1 diabetes from March 1, 2020, to Aug 31, 2021. In the reference period, which comprised three similar 18-month terms (from March 1, 2014, to Aug 31, 2015; March 1, 2016, to Aug 31, 2017; and March 1, 2018, to Aug 31, 2019) 2096 children and adolescents were diagnosed. The incidence of type 1 diabetes was 61·0 per 100 000 person-years (95% CI 56·8-65·4) among children younger than 15 years old during the pandemic, which was significantly higher than during the reference period (52·3 per 100 000 person-years; 50·1-54·6). The incidence rate ratio adjusted for age and sex for the COVID-19 pandemic was 1·16 (1·06-1·25; p=0·0006) when compared with the reference period. The children diagnosed during the COVID-19 pandemic had more often diabetic ketoacidosis (p<0·001), had a higher HbA (p<0·001), and tested more frequently positive for glutamic acid debarboxylase antibodies at diagnosis (p<0·001) than those diagnosed before the pandemic. There were no significant differences in the distribution of HLA genotypes between the two periods. Only five of those diagnosed during the pandemic (0·9%) of 583 tested positive for infection-induced SARS-CoV-2 antibodies.

INTERPRETATION

Children and adolescents diagnosed with type 1 diabetes during the pandemic had a more severe disease at diagnosis. The observed increase in type 1 diabetes incidence during the first 18 months could be a consequence of lockdown and physical distancing rather than a direct effect of SARS-CoV-2 infection.

FUNDING

Helsinki University Hospital Research Funds, EU Horizon 2020 (Versatile emerging infectious disease observatory project), Academy of Finland, Sigrid Jusélius Foundation, Jane & Aatos Erkko Foundation, and Medicinska understödsföreningen Liv och Hälsa.

TRANSLATIONS

For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

摘要

背景

一些流行病学研究表明,在 COVID-19 大流行期间 1 型糖尿病的发病率有所增加,但尚不清楚这种增加的机制。在这项研究中,我们旨在评估 SARS-CoV-2 病毒在报告的 1 型糖尿病发病率增加中可能发挥的作用。

方法

本研究采用芬兰儿科糖尿病登记处(FPDR)的数据,评估了芬兰年龄在 15 岁以下儿童在 COVID-19 大流行的前 18 个月中(大流行期间每 100000 人年新诊断 1 型糖尿病的儿童人数和参考期)1 型糖尿病(新诊断的 1 型糖尿病患者中,有确诊单基因糖尿病的儿童被排除在外。我们还比较了这两个队列之间疾病的表型和 HLA 基因型,并分析了新诊断的 1 型糖尿病患者中 SARS-CoV-2 抗体检测呈阳性的比例。

结果

2020 年 3 月 1 日至 2021 年 8 月 31 日,芬兰有 785 名儿童和青少年被诊断患有 1 型糖尿病。在参考期内,有 2096 名儿童和青少年被诊断患有 1 型糖尿病,该参考期由三个相似的 18 个月时段组成(2014 年 3 月 1 日至 2015 年 8 月 31 日;2016 年 3 月 1 日至 2017 年 8 月 31 日;2018 年 3 月 1 日至 2019 年 8 月 31 日)。在 COVID-19 大流行期间,15 岁以下儿童的 1 型糖尿病发病率为 61.0/100000 人年(95%CI 56.8-65.4),明显高于参考期(52.3/100000 人年;50.1-54.6)。调整年龄和性别后,COVID-19 大流行期间的发病率比值比为 1.16(1.06-1.25;p=0.0006)。与大流行前相比,在 COVID-19 大流行期间诊断出的儿童更常患有糖尿病酮症酸中毒(p<0.001),HbA 更高(p<0.001),谷氨酸脱羧酶抗体检测呈阳性的频率更高(p<0.001)。两个时期 HLA 基因型的分布无显著差异。在大流行期间被诊断出的 583 名儿童中,只有 5 名(0.9%)检测到感染诱导的 SARS-CoV-2 抗体呈阳性。

结论

在大流行期间被诊断患有 1 型糖尿病的儿童在诊断时病情更严重。在最初的 18 个月中观察到 1 型糖尿病发病率的增加可能是封锁和身体距离的结果,而不是 SARS-CoV-2 感染的直接结果。

资助

赫尔辛基大学医院研究基金、欧盟地平线 2020 计划(多功能传染病观测站项目)、芬兰科学院、西格里德·朱塞利乌斯基金会、简和阿托斯·埃尔科基金会、生命与健康医学支持基金会。

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