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; 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.

项目摘要 在艾滋病毒（PLHIV）的患者中，患糖尿病前和糖尿病的风险更高。它 据估计，大约50％的流行糖尿病病例，甚至更高的水平 在低收入和中等收入国家（LMIC）中，糖尿病前期尤其没有诊断。经验证据 表明，过度依赖葡萄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）包括糖基化 血红蛋白（HBA1C）在其诊断和监测糖尿病的建议中测试。这 HBA1C测试被认为是早期检测糖尿病的高价 临床实践，包括LMIC。但是，目前不建议在 PLHIV由于不可靠的结果归因于该人群中血红蛋白水平较低的结果。主要目标 拟议的研究是确定有关血红蛋白水平层和 炎症，胰岛素抵抗和免疫治疗状态的标志。果糖，另一种糖化的 也将评估没有血红蛋白限制的测试。这将通过 以下特定目的：目标1：利用血液图和其他生物标志物分层来确定最佳 糖尿病和糖尿病前糖尿病的HBA1C诊断阈值和患有艾滋病毒的人。 AIM 2：确定糖尿病和糖尿病前期糖尿病的最佳果糖诊断阈值 与艾滋病毒一起生活的人。目标3：检查将HBA1C与HBA1C相结合的诊断精度 果糖测试评估血糖症并开发一种基于 生物标志物水平。一个多学科的研究人员组成了该项目，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，临床专家 马里兰大学的化学和传染病流行病学，人类病毒学研究所 尼日利亚（IHVN）和分支机构学术和临床中心的本地研究人员。我们正在采用交叉 招募992 PLHIV的分区设计以及年龄和性别匹配的770人没有艾滋病毒 IHVN的合作伙伴阿布贾大学教学医院。一份全面的问卷 将管理WHO逐步接近工具（步骤）的相关组件。血液样本 将收集用于HBA1C和果糖测试，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）。 HBA1C的结果， 果糖胺和OGTT，后者作为黄金标准，将用于生成接收器操作 特征性（ROC）曲线以确定基于生物标志物地层的最佳切割。这个项目将导致 使用HBA1C和/或果糖与生物标志物水平结合使用HBA1C和/或果糖素，可实现强大的测试制度 PLHIV中糖尿病和糖尿病前期的筛查。