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.

项目概要 艾滋病毒感染者（PLHIV）患糖尿病前期和糖尿病的风险较高。它 据估计，大约 50% 的糖尿病患病病例，甚至更高的水平 糖尿病前期仍未得到诊断，特别是在低收入和中等收入国家 (LMIC)。经验证据 表明过度依赖血糖测量可能是诊断不良的部分原因。世界 卫生组织 (WHO) 和国际糖尿病联合会 (IDF) 已将糖基化 血红蛋白 (HbA1c) 测试是其诊断和监测糖尿病的建议。这 HbA1c 检测被认为对于糖尿病的早期检测非常有价值，并且在以下领域被广泛采用： 包括中低收入国家的临床实践。然而，目前不建议在以下人群中使用 HbA1c 测试： 由于该人群血红蛋白水平较低，导致结果不可靠，导致感染艾滋病毒。主要目标是 拟议的研究旨在确定血红蛋白水平层的适当 HbA1c 诊断阈值和 炎症、胰岛素抵抗和免疫病毒学状态的标志物。果糖胺，糖化的替代品 还将评估没有血红蛋白限制的测试。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分层 HIV 感染者和未感染者中糖尿病和糖尿病前期的 HbA1c 诊断阈值。 目标 2：确定糖尿病和糖尿病前期的最佳果糖胺诊断阈值 感染和未感染艾滋病毒的人。目标 3：检查 HbA1c 与 果糖胺测试用于评估血糖异常，并开发一种算法来指导测试 生物标志物水平。该项目已组建了一个多学科研究团队，其中包括 国际公认的艾滋病毒、非传染性疾病、糖尿病学/内分泌学、临床 马里兰大学人类病毒学研究所的化学和传染病流行病学 尼日利亚 (IHVN) 以及附属学术和临床中心的当地研究人员。我们正在雇用一个跨 分段设计招募 992 名艾滋病毒感染者以及年龄和性别匹配的 770 名非艾滋病毒感染者 阿布贾大学教学医院是 IHVN 的合作伙伴。一份综合调查问卷 将管理世卫组织逐步方法工具（STEPS）的相关组成部分。血液样本 将收集用于 HbA1c 和果糖胺测试以及口服葡萄糖耐量测试 (OGTT) 和相关 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）。 HbA1c 结果， 果糖胺和 OGTT（后者作为金标准）将用于生成接收器操作 特征（ROC）曲线，根据生物标志物层确定最佳截止值。该项目将导致 稳健的测试制度，使用 HbA1c 和/或果糖胺与生物标志物水平相结合，以确保有效 艾滋病毒携带者中的糖尿病和糖尿病前期筛查。