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

项目摘要 艾滋病毒感染者患糖尿病前期和糖尿病的风险较高。它 据估计，大约50%的糖尿病流行病例， 糖尿病前期仍然未被诊断，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佳的部分原因。世界 世界卫生组织（WHO）和国际糖尿病联合会（IDF）已经将糖基化的 血红蛋白（HbA1c）测试在糖尿病诊断和监测的建议。的 HbA1c测试被认为对糖尿病的早期检测非常有价值，并且在糖尿病患者中被广泛采用。 临床实践，包括LMIC。然而，HbA1c测试目前不推荐用于 由于该人群血红蛋白水平较低，结果不可靠，导致感染艾滋病毒。的主要目标 拟议的研究旨在确定血红蛋白水平分层的适当HbA1c诊断阈值， 炎症、胰岛素抵抗和免疫病毒学状态的标志物。果糖胺，一种替代糖化 测试，没有血红蛋白的限制，也将进行评估。这将通过以下方式实现： 目标1：利用血象和其他生物标志物分层来确定最佳的 在HIV感染者和非HIV感染者中，HbA1c诊断糖尿病和前驱糖尿病的阈值。 目的2：确定糖尿病和糖尿病前期的最佳果糖胺诊断阈值， 感染和未感染艾滋病毒的人。目的3：检查HbA1c与 果糖胺测试用于评估功能障碍，并开发一种算法来指导测试， 生物标志物水平。为此项目组建了一个多学科研究小组，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，来自马里兰州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。我们正在使用一个十字架- 采用分层设计，在2009年12月至2010年12月期间招募992名艾滋病毒感染者沿着，以及年龄和性别匹配的770名无艾滋病毒感染者。 阿布贾大学教学医院，IHVN的合作伙伴。一份综合问卷， 将使用世卫组织逐步方法工具（STEPS）的相关组成部分。血样 将采集HbA1c和果糖胺检测沿着口服葡萄糖耐量试验（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，将用于产生接收器操作 使用特征（ROC）曲线来确定基于生物标志物层的最佳截止值。该项目将导致 使用HbA1c和/或果糖胺结合生物标志物水平的稳健检测方案， 艾滋病病毒感染者糖尿病和糖尿病前期筛查。

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.