Urinary F2-isoprostanes as a new biomarker for the risk of type 2 diabetes

描述（由申请人提供）：识别发生2型糖尿病（T2DM）的高风险个体对于有效的靶向干预至关重要。我们建议验证尿F2-异前列腺素（F2- isops）是T2DM风险的生物标志物的假设。在一项初步研究中，我们发现尿F2-IsoPs基线水平与T2DM发病率呈负相关；在调整年龄、体重指数和糖耐量受损（IGT）状态后，T2DM的几率为0.32 （95% CI, 0.12-0.81）。这种关联在正常（NGT）和IGT亚组中相似：or分别为0.23和0.34。我们的数据表明，诊断前F2-IsoP水平较低的个体发展为T2DM的风险增加了3倍。我们发表了一个假设来解释这些结果，并预测尿F2-IsoPs也与IGT和体重增加的风险呈负相关。我们建议将我们的试点研究扩展到整个符合条件的IRAS队列（n=900）。我们的主要目的是验证尿F2-IsoPs与T2DM风险负相关的假设。次要的具体目的是评估F2-IsoPs与两个结果之间的前瞻性关联：IGT和体重增加。尿液中F2-IsoPs的水平将通过最近开发的高通量UPLC-MS/MS方法进行测量。这项研究为开发一种新的非侵入性生物标志物尿液F2-IsoPs提供了一个重要的机会，它有可能预测糖尿病的风险（超出已知的风险因素）和体重增加，这是一个没有生物标志物可用的结果。2型糖尿病正在成为一种具有破坏性后果的全球性流行病。通过生活方式和药物干预可以预防这种疾病。因此，需要进行大量的工作来识别高危人群。这项拟议的研究为开发一种新的生物标志物提供了机会，即尿液中F2-IsoPs的水平，它有可能预测已知危险因素之外的糖尿病风险。重要的是，这种生物标志物是非侵入性的，可以用于临床环境。我们也相信这种生物标记物可以用来预测体重增加，这是一个非常重要的特征，没有生物标记物可用。

DESCRIPTION (provided by applicant): Identifying individuals at high risk of developing type 2 diabetes (T2DM) is critical for effective targeted interventions. We propose to test the hypothesis that urinary F2- isoprostanes (F2-IsoPs) are a biomarker for the risk of T2DM. In a pilot study, we found that baseline levels of urinary F2-IsoPs are inversely associated with incident T2DM; after adjustment for age, body mass index, and impaired glucose tolerance (IGT)-status, the odds of T2DM was 0.32 (95% CI, 0.12-0.81). This association was similar in the normal (NGT) and IGT sub-groups: ORs were 0.23 and 0.34, respectively. Our data suggest that individuals with lower F2-IsoP levels prior to diagnosis have a 3-fold increased risk for developing T2DM. We published a hypothesis that explains these results and predicts that urinary F2-IsoPs are also inversely associated with the risks of IGT and weight gain. We propose to expand our pilot study to the entire eligible IRAS cohort (n=900). Our primary specific aim is to test the hypothesis that urinary F2-IsoPs are inversely associated with the risk of T2DM. The secondary specific aims are to assess prospective associations between F2-IsoPs and two outcomes: IGT and weight gain. Urinary levels of F2-IsoPs will be measured by a recently developed, high-throughput UPLC-MS/MS method. The proposed research offers an important opportunity to develop a new non- invasive biomarker, urinary F2-IsoPs, which has the potential to predict the risks of diabetes (beyond the known risk factors) and of weight gain, an outcome for which no biomarker is available. PUBLIC HEALTH RELEVANCE Type 2 diabetes is becoming a global epidemic with devastating consequences. Prevention of this disease is possible through lifestyle and pharmacological interventions. Therefore, there is an intensive effort to identify people at high risk. The proposed research offers an opportunity to develop a new biomarker, urinary levels of F2-IsoPs, which has the potential to predict the risk of diabetes beyond the known risk factors. Importantly, this biomarker is non-invasive and can be used in a clinical setting. We also believe that this biomarker can be used to predict weight gain, a very important characteristic for which no biomarkers are available.