Biomarker-Guided Evaluation of Glycated Testing Modalities for Dysglycemia among Persons Living with HIV (BEGET)

HIV 感染者血糖异常的生物标志物引导糖化检测方式评估 (BEGET)

• 批准号: 10751444
• 负责人: JIBREEL JUMARE
• 金额: $ 22.75万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751444
• 关键词: Address; Adopted; Age; Algorithms; Area Under Curve; Biological Markers; Blood specimen; C-reactive protein; CD4 Lymphocyte Count; Clinical Chemistry; Collaborations; Data; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Early Diagnosis; Endocrinology; Evaluation; Fasting; Fructosamine; General Population; Glucose; Glucose tolerance test; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Guidelines; HIV; Hemoglobin; Hemoglobin concentration result; Human; Individual; Infectious Disease Epidemiology; Insulin; Insulin Resistance; International; Kidney Diseases; Maryland; Measures; Microvascular Dysfunction; Modality; Monitor; Newly Diagnosed; Nigeria; OGTT; Outcome; Performance; Persons; Population; Prediabetes syndrome; Predictive Value; Questionnaires; RNA; ROC Curve; Recommendation; Reporting; Research Personnel; Retinal Diseases; Risk; Sensitivity and Specificity; Serum Proteins; Specificity; Teaching Hospitals; Testing; Universities; World Health Organization; clinical care; clinical center; clinical practice; cohort; design; diabetic; diagnostic accuracy; glycation; improved; inflammatory marker; instrument; low and middle-income countries; multidisciplinary; recruit; screening; sex; systemic inflammatory response; tool; trend; virology

PROJECT SUMMARY The risk of developing prediabetes and diabetes mellitus is higher among persons living with HIV (PLHIV). It has been estimated that about 50% of prevalent cases of diabetes mellitus, and an even higher level for prediabetes, remain undiagnosed particularly in low- and middle-income countries (LMICs). Empirical evidence suggests that over-reliance on glucose measures may be partly responsible for the poor diagnosis. The World Health Organization (WHO) and the International Federation of Diabetes (IDF) have included the glycosylated hemoglobin (HbA1c) test in their recommendations for diagnosis and monitoring of diabetes mellitus. The HbA1c test is considered highly valuable for early detection of diabetes and is becoming widely adopted in clinical practice including in LMICs. However, the HbA1c test is currently not recommended for use among PLHIV due to unreliable results attributable to the lower hemoglobin levels in this population. The major goal of the proposed study is to identify appropriate HbA1c diagnostic thresholds for strata of hemoglobin levels and markers of inflammation, insulin resistance and immuno-virologic status. Fructosamine, an alternative glycated test, which has no hemoglobin limitation, will also be evaluated. This will be accomplished through the following specific aims: Aim 1: Utilize hemogram and other biomarker stratifications to determine optimal HbA1c diagnostic thresholds for diabetes mellitus and prediabetes among persons living with and without HIV. Aim 2: Determine optimal fructosamine diagnostic thresholds for diabetes mellitus and prediabetes among persons living with and without HIV. Aim 3: Examine the diagnostic accuracy of combining HbA1c with fructosamine tests for the assessment of dysglycemia and develop an algorithm to guide testing based on biomarker levels. A multidisciplinary team of researchers has been assembled for this project, comprising internationally recognized experts in HIV, non-communicable diseases, diabetology/endocrinology, clinical chemistry, and infectious disease epidemiology from the University of Maryland, Institute of Human Virology Nigeria (IHVN) and local researchers from affiliate academic and clinical centers. We are employing a cross- sectional design to recruit 992 PLHIV along with age- and sex-matched 770 persons without HIV at the University of Abuja Teaching Hospital, a collaborating partner of IHVN. A comprehensive questionnaire with relevant components of the WHO stepwise approach instrument (STEPS) will be administered. Blood samples will be collected for HbA1c and fructosamine tests along with oral glucose tolerance test (OGTT) and relevant biomarkers (hemoglobin, serum proteins, c-reactive protein, insulin, CD4 count, HIV RNA). Results of HbA1c, fructosamine and OGTT, with the latter as gold standard, will be used to generate receiver operating characteristic (ROC) curves to determine optimal cut-offs based on biomarker strata. This project will result in a robust testing regime, using HbA1c and/or fructosamine in conjunction with biomarker levels, for valid screening of diabetes and prediabetes among PLHIV.

项目总结 艾滋病毒携带者患糖尿病前期和糖尿病的风险更高。它 据估计，大约50%的糖尿病流行病例，甚至更高的水平 糖尿病前期疾病仍未得到诊断，特别是在低收入和中等收入国家。经验证据 这表明过度依赖血糖检测可能是诊断不佳的部分原因。世界 卫生组织(WHO)和国际糖尿病联合会(IDF)已将糖基化 糖化血红蛋白(HbA1c)检测在糖尿病诊断和监测中的建议。这个 糖化血红蛋白检测被认为对糖尿病的早期发现具有很高的价值，并在 包括LMICs在内的临床实践。然而，目前不建议将HbA1c检测用于 PLHIV是由于这一人群中较低的血红蛋白水平导致的不可靠的结果。的主要目标是 这项拟议的研究旨在确定适当的HbA1c诊断阈值，以确定不同水平的血红蛋白水平和 炎症、胰岛素抵抗和免疫病毒学状态的标志物。果糖胺，一种糖化的替代品 测试，没有血红蛋白限制，也将进行评估。这将通过 以下具体目标：目标1：利用血象和其他生物标志物分层来确定最佳 HbA1c诊断HIV携带者和非HIV携带者糖尿病和糖尿病前期的阈值。 目的2：确定糖尿病和糖尿病前期的最佳果糖胺诊断阈值 艾滋病毒携带者和未携带艾滋病毒者。目的3：检查糖化血红蛋白与糖化血红蛋白联合诊断的准确性 果糖胺试验用于评估血糖紊乱，并开发一种算法来指导基于 生物标志物水平。为这一项目组建了一个多学科的研究小组，包括 国际公认的艾滋病毒、非传染性疾病、糖尿病/内分泌学、临床 化学和传染病流行病学，来自马里兰大学人类病毒学研究所 尼日利亚(IHVN)和来自附属学术和临床中心的当地研究人员。我们雇佣了一个交叉人- 分段设计招募992名艾滋病病毒携带者以及770名年龄和性别匹配的非艾滋病病毒携带者 阿布贾大学教学医院，IHVN的合作伙伴。一份全面的调查问卷，包括 将实施世卫组织逐步方法文书(STEPS)的相关组成部分。血液样本 将收集用于糖化血红蛋白和果糖胺测试以及口服葡萄糖耐量测试(OGTT)和相关的 生物标志物(血红蛋白、血清蛋白、C反应蛋白、胰岛素、CD4计数、HIV RNA)。糖化血红蛋白检测结果， 以后者为黄金标准的果糖胺和OGTT将用于产生接收器操作 特征(ROC)曲线，以确定基于生物标志物地层的最佳截止范围。这个项目将导致一个 可靠的检测制度，结合使用HbA1c和/或果糖胺以及生物标志物水平，以确保有效 在PLHIV中筛查糖尿病和糖尿病前期。