Utilization of electronic health records for the assessment of adiponectin receptor autoantibodies during the progression of cardio-metabolic comorbidities.

Michael J Pugia, Meeta Pradhan, Rong Qi, Doreen L Eastes, Anna Vorsilak, Bradley J Mills, Zane Baird, Aruna Wijeratne, Scott M McAhren, Amber Mosley, Anantha Shekhar, Daniel H Robertson
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Abstract

Background: Diabetes is a complex, multi-symptomatic disease whose complications drives increases in healthcare costs as the diabetes prevalence grows rapidly world-wide. Real-world electronic health records (EHRs) coupled with patient biospecimens, biological understanding, and technologies can characterize emerging diagnostic autoimmune markers resulting from proteomic discoveries.

Methods: Circulating autoantibodies for C-terminal fragments of adiponectin receptor 1 (IgG-CTF) were measured by immunoassay to establish the reference range using midpoint samples from 1862 participants in a 20-year observational study of type 2 diabetes and cardiovascular arterial disease (CVAD) conducted by the Fairbanks Institute. The White Blood Cell elastase activity in these patients was assessed using immunoassays for Bikunin and Uristatin. Participants were assigned to four cohorts (healthy, T2D, CV, CV+T2D) based on analysis of their EHRs and the diagnostic biomarkers values and patient status were assessed ten-years post-sample.

Results: The IgG-CTF reference range was determined to be 75-821 ng/mL and IgG-CTF out-of-range values did not predict cohort or comorbidity as determined from the EHRs at 10 years after sample collection nor did IgG-CTF demonstrate a significant risk for comorbidity or death. Many patients at sample collection time had other conditions (hypertension, hyperlipidemia, or other risk factors) of which only hypertension, Uristatin and Bikunin values correlated with increased risk of developing additional comorbidities (odds ratio 2.58-13.11, P<0.05).

Conclusions: This study confirms that retrospective analysis of biorepositories coupled with EHRs can establish reference ranges for novel autoimmune diagnostic markers and provide insights into prediction of specific health outcomes and correlations to other markers.

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利用电子健康记录评估心血管代谢合并症发展过程中的脂肪连接素受体自身抗体。
背景:糖尿病是一种复杂、多症状的疾病,随着全球糖尿病患病率的快速增长,其并发症导致医疗费用的增加。真实世界的电子健康记录(EHR)与患者生物标本、生物学理解和技术相结合,可以确定蛋白质组发现的新兴诊断性自身免疫标记物的特征:费尔班克斯研究所(Fairbanks Institute)对2型糖尿病和心血管动脉疾病(CVAD)进行了一项长达20年的观察研究,通过免疫测定法测定了脂肪连蛋白受体1(IgG-CTF)C末端片段的循环自身抗体,并利用1862名参与者的中点样本确定了参考范围。使用比库宁和乌司他丁免疫测定法对这些患者的白细胞弹性蛋白酶活性进行了评估。根据对参与者电子病历的分析,将他们分配到四个队列(健康、T2D、CV、CV+T2D),并在取样后十年对诊断生物标志物值和患者状况进行评估:IgG-CTF的参考范围被确定为75-821纳克/毫升,IgG-CTF超出范围的值并不能预测样本采集后10年的电子病历所确定的队列或合并症,IgG-CTF也没有显示出合并症或死亡的显著风险。许多患者在采集样本时还患有其他疾病(高血压、高脂血症或其他风险因素),其中只有高血压、尿司他丁和比库宁值与其他合并症的发病风险增加相关(几率比 2.58-13.11,PConclusions:这项研究证实,结合电子病历对生物库进行回顾性分析,可以为新型自身免疫诊断标记物确定参考范围,并为预测特定的健康结果以及与其他标记物的相关性提供见解。
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