Urinary F2-Isoprostanes As A New Biomarker For The Risk Of Type 2 Diabetes

描述(由申请人提供)：确定罹患2型糖尿病(T2 DM)的高危人群对于有效的针对性干预至关重要。我们建议检验尿F2-异前列腺素(F2-Isoprostanes，F2-Isoprostanes，F2-Isoprostanes)是T2 DM风险的生物标记物的假设。在一项初步研究中，我们发现尿F2-Isop的基线水平与T2 DM发病呈负相关；在调整了年龄、体重指数和糖耐量受损(IGT)状态后，T2 DM的几率为0.32(95%CI，0.12-0.81)。这种相关性在正常(NGT)和IGT亚组中相似：OR值分别为0.23和0.34。我们的数据表明，诊断前F2-IsoP水平较低的人患T2 DM的风险增加3倍。我们发表了一项假说，解释了这些结果，并预测尿液F2-Isop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大到整个符合条件的IRA队列(n=900)。我们的主要目标是验证尿F2-Isop与T2 DM风险负相关的假设。次要的具体目标是评估F2-Isop与两种结果之间的预期关联：IGT和体重增加。尿中F2-Isop的水平将通过最近开发的一种高通量UPLC-MS/MS方法来测量。这项拟议的研究为开发一种新的非侵入性生物标记物--尿F2-IsoPs提供了一个重要机会，该标记物有可能预测糖尿病(超出已知危险因素)和体重增加的风险，而这一结果尚无生物标记物可用。与公共卫生相关的2型糖尿病正在成为一种具有破坏性后果的全球流行病。通过生活方式和药物干预可以预防这种疾病。因此，有一项密集的努力来识别高危人群。这项拟议的研究为开发一种新的生物标记物--尿F2-Isop水平提供了机会，该标记物有可能在已知危险因素之外预测糖尿病的风险。重要的是，这种生物标志物是非侵入性的，可以在临床环境中使用。我们还认为，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，但还没有可用的生物标记物。

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.