Nanoparticle Diagnostics Laboratory, Institute for Cardiovascular & Metabolic Diseases, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
Department of Clinical Laboratory Science, College of Allied Health Sciences, East Carolina University, Greenville, NC, 27834, USA.
J Transl Med. 2017 Dec 19;15(1):258. doi: 10.1186/s12967-017-1359-5.
Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement.
Water T, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression.
Plasma and serum water T exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma.
Water T detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.
代谢综合征（MetS）是一种高度普遍的病症，可识别出患有 2 型糖尿病和动脉粥样硬化性心血管疾病的风险人群。这些疾病的预防依赖于早期检测和干预，以保护胰岛β细胞和动脉壁完整性。然而，MetS 的临床标准对胰岛素抵抗、炎症、胆固醇和凝血因子异常等特征性的 2 型糖尿病和动脉粥样硬化进展的早期阶段不敏感。在这里，我们报告了一种新型非典型生物标志物的发现和初步特征，该标志物仅通过一次测量即可检测到这些早期状态。
使用台式核磁共振弛豫度测量仪，在几分钟内测量水 T，对血液蛋白质组的代谢变化非常敏感。在一项对 72 名非糖尿病人类受试者的观察性横断面研究中，使用双变量、多变量和逻辑回归分析了血浆和血清水 T 值与超过 130 种血液生物标志物的关联。
血浆和血清水 T 与胰岛素、脂质、炎症、凝血和电解质平衡的标志物呈强烈的双变量相关性。在纠正混杂因素后，低水 T 值与空腹高胰岛素血症、血脂异常和亚临床炎症独立且呈累加性相关。血浆水 T 对血糖正常受试者（McAuley 指数定义）的早期胰岛素抵抗具有 100%的敏感性和 87%的特异性。通过低水 T 值识别出 16 名早期代谢异常的血糖正常受试者（研究人群的 22%）。其中 13 名不符合代谢综合征的协调临床标准，这将被传统的糖尿病风险筛查遗漏。低水 T 值与血浆中 16 种最丰富的急性相蛋白和脂蛋白中的 6 种的平均浓度升高相关。
水 T 检测到与代谢综合征相关的一系列早期异常，提供了个体代谢健康的整体视图。它规避了空腹血糖和糖化血红蛋白的陷阱，以及当前代谢综合征临床标准的局限性。水 T 有望成为一种早期、全面且实用的筛查工具，用于识别患有糖尿病和动脉粥样硬化风险的个体。
