PDF(Pubmed)
Abstract：
Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this \"domino effect\". Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the \"diagnostic tree\" (yes/no) applicable to healthrisk assessment in diabetes care.
摘要：
2型糖尿病（T2DM）定义为主要不是胰岛素依赖性的成人发作型，占所有糖尿病(DM)病例的95%以上。根据全球记录,5.37亿20-79岁的成年人受到DM的影响，这意味着15人中至少有1人受到DM的影响。预计到2045年，这一数字将增长51％。T2DM最常见的并发症之一是糖尿病性视网膜病变（DR），总患病率超过30％。与DR相关的视力障碍的总数正在上升，由于T2DM人口的增长。增殖性糖尿病视网膜病变（PDR）是进行性DR，也是工作年龄成年人可预防失明的主要原因。此外，PDR具有特征性系统属性，包括线粒体损伤，增加细胞死亡和慢性炎症，是缺血性卒中等级联DM并发症的独立预测因子。因此,早期DR是出现在“多米诺效应”上游的可靠预测因子。全球筛查，导致及时识别DM相关并发症，目前应用的反应性药物没有充分实施。个性化的预测方法和具有成本效益的有针对性的预防短期预测，预防和个性化医疗(PPPM/3PM)可以很好地利用积累的知识，防止失明和其他严重的DM并发症。为了达到这个目标,需要可靠的阶段和疾病特异性生物标志物面板，其特征在于样品收集的简单方式，分析的高灵敏度和特异性。在目前的研究中,我们检验了以下假设:非侵入性收集的泪液是分析眼部和全身(DM相关并发症)生物标志物模式的可靠来源,适用于鉴别诊断稳定性DR和PDR.这里,我们报告了正在进行的全面研究的第一个结果，其中我们将个性化的患者概况(健康对照与稳定D患者以及有或没有合并症的PDR患者)与其在泪液中的代谢概况相关联。进行的比较质谱分析确定了以下代谢簇，这些代谢簇在比较组中差异表达：酰基肉碱，氨基酸及相关化合物，胆汁酸，神经酰胺,溶血磷脂酰胆碱，核碱基及相关化合物，磷脂酰胆碱,甘油三酯，胆固醇酯，和脂肪酸。我们的初步数据强烈支持泪液中代谢模式的潜在临床应用，表明DR分期和PDR进展具有独特的代谢特征。这项初步研究创建了一个平台，用于验证泪液生物标志物模式，以对倾向于PDR的T2DM患者进行分层。此外，由于PDR是缺血性卒中等严重T2DM相关并发症的独立预测因子,我们的国际项目旨在为"诊断树"(是/否)创建适用于糖尿病护理健康风险评估的分析原型.
