HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children.

IF 3.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pediatric Diabetes Pub Date : 2022-12-01 Epub Date: 2022-09-21 DOI:10.1111/pedi.13413

Falastin Salami, Roy Tamura, Lu You, Åke Lernmark, Helena Elding Larsson, Markus Lundgren, Jeffrey Krischer, Anette-Gabriele Ziegler, Jorma Toppari, Riitta Veijola, Marian Rewers, Michael J Haller, William Hagopian, Beena Akolkar, Carina Törn

{"title":"HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children.","authors":"Falastin Salami, Roy Tamura, Lu You, Åke Lernmark, Helena Elding Larsson, Markus Lundgren, Jeffrey Krischer, Anette-Gabriele Ziegler, Jorma Toppari, Riitta Veijola, Marian Rewers, Michael J Haller, William Hagopian, Beena Akolkar, Carina Törn","doi":"10.1111/pedi.13413","DOIUrl":null,"url":null,"abstract":"Objective: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.Research design and methods: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.Results: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001).Conclusion: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.","PeriodicalId":19797,"journal":{"name":"Pediatric Diabetes","volume":"23 8","pages":"1586-1593"},"PeriodicalIF":3.9000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/2a/PEDI-23-1586.PMC9772117.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/pedi.13413","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/21 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.

Research design and methods: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.

Results: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001).

Conclusion: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.

Abstract Image

查看原文本刊更多论文

HbA1c作为血清转化的TEDDY儿童中额外胰岛自身抗体和1型糖尿病的时间预测生物标志物。

目的：糖化血红蛋白（HbA1c）水平的升高与1型糖尿病的发作有关，而1型糖尿病发作之前会出现一到几种针对胰岛β细胞自身抗原的自身抗体；胰岛素（IA）、谷氨酸脱羧酶（GAD）、胰岛抗原-2（IA-2）和锌转运蛋白8（ZnT8）。诊断为1型糖尿病的风险随着自身抗体数量的增加而增加。需要预测第二种或随后的自身抗体和1型糖尿病发展的生物标志物来预测疾病阶段并改进二级预防试验。本研究旨在调查参与青年糖尿病环境决定因素（TEDDY）研究的健康儿童的HbA1c是否可能预测从第一个自身抗体或1型糖尿病发展到随后的自身抗体或2型糖尿病。研究设计和方法：设计了一个联合模型来评估健康儿童从出生到15岁的纵向HbA1c水平与第一种（胰岛素或GAD自身抗体）到第二种、第二种到第三种、第三种到第四种自身抗体或1型糖尿病的发展之间的关系年龄。结果：发现HbA1c水平升高与1型糖尿病的高风险相关（HR 1.82，95%CI[1.57-2.10]，p 结论：总之，HbA1c升高是1型糖尿病发病的可靠时间预测指标。HbA1c从第一种自身抗体到第三种自身抗体的增加率增加以及HbA1c的降低预测了IA-2A的发展，这是新的发现，证明了HbA1c与自身抗体的出现之间的联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pediatric Diabetes 医学-内分泌学与代谢

CiteScore

6.60

自引率

14.70%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.