Caloric Restriction Biomarkers Predict Type II Diabetes?

热量限制生物标志物可预测 II 型糖尿病？

• 批准号: 7071034
• 负责人: BRUCE S KRISTAL
• 金额: $ 55.73万
• 依托单位: WINIFRED MASTERSON BURKE MED RES INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7071034
• 关键词: aging; biomarker; caloric dietary content; clinical research; dietary restriction; disease /disorder proneness /risk; human tissue; mass spectrometry; noninsulin dependent diabetes mellitus; nutrition related tag; proteomics; serology /serodiagnosis

DESCRIPTION (provided by applicant): The risk of developing Type II diabetes is increased 16-fold by obesity and approximately 10-fold by aging. Dietary restriction (DR, long term, low calorie diets) has established efficacy in delaying aging and in reducing neoplastic disease in lab rodents. We have now identified 93 components of the sera metabolome that define a DR serotype - i.e., a metabolic serotype that reflects caloric intake. Multivariate pattern recognition analysis has identified profiles that distinguish ad libitum fed (AL) and DR rats (100% accuracy in training sets, mean >90% in test sets), and enabled construction of accurate models of intermediate intakes (1^=0.88) for individual rats. Initial sera proteome profiles also distinguish diet with 100% accuracy,. The robust, systemic effects of DR suggest that a subset of the metabolites in sera that distinguish diet will reflect, even across species, the physiological benefits of reduced caloric intake. We have established an interdisciplinary, multi-site team of investigators to test the two-part hypothesis that 1) serum metabolite profiles that reflect long-term caloric intake in rats will predict relative risk of human disease (specific test case: Type II diabetes), and; 2) the components of these profiles are limited to a small subset of discrete metabolic pathways. Work on the latter sets the stage for understanding metabolic pathways involved in protective effects of DR against diabetes. The three Aims are: Aim 1. To complete characterization of metabolic serotypes based on both the proteome and the metabolome, and to adapt these profiles for human epidemiological studies. Both individual serum constituents (proteins and metabolites) and their cognate metabolic profiles will be validated for studies using human samples. Aim 2. To determine the extent to which metabolic profiles that are reflective of or independent of lone-term caloric intake predict type II diabetes in nested case control studies (Hypothesis, part 1) '< We will evaluate the ability of expert systems trained to recognize serotypes reflecting long term caloric . intake to determine relative risk for future Type II diabetes in sera from 1000 paired cases and controls from well-characterized human populations (Nurses'Health Study). j ,- i i Aim 3 To determine the biochemical identity of critical serum markers (Hypothesis, part 2) . 'i. Mass spectroscopy will be used to identify critical protein and small molecule components ofmetabolic serotypes that characterize DR in rats and relative type II diabetes risk in humans '

描述（由申请人提供）： 肥胖症的II型糖尿病的风险增加了16倍，而衰老的风险大约增加了10倍。饮食限制（DR，长期，低卡路里饮食）在延迟衰老和减少实验室啮齿动物的肿瘤疾病方面确立了功效。现在，我们已经确定了Sera代谢组的93个成分，这些成分定义了DR血清型 - 即反映热量摄入量的代谢血清型。多元模式识别分析已经确定了区分自由饲料（AL）和DR大鼠（训练集的精度为100％，平均值> 90％）的曲线，并启用了单个大鼠的准确模型（1^= 0.88）。最初的血清蛋白质组曲线还以100％精度区分饮食。 DR的强大，全身作用表明，分歧饮食的一部分代谢产物的一部分将反映出饮食的生理效果也将反映出饮食的生理益处。我们已经建立了一个跨学科的多站点研究人员团队，以测试两部分的假设，即1）反映大鼠长期热量摄入的血清代谢产物特征将预测人类疾病的相对风险（特定的测试案例：II型糖尿病），以及； 2）这些轮廓的组成部分仅限于一小部分离散代谢途径。后者的工作为理解DR针对糖尿病的保护作用涉及的代谢途径奠定了基础。这三个目的是：目标1。基于蛋白质组和代谢组的代谢血清型的完整表征，并将这些特征适应人类流行病学研究。单个血清成分（蛋白质和代谢产物）及其同源代谢谱均可用于使用人类样品进行研究。目的2。确定反映或独立于孤独的热量摄入的代谢特征的程度，可以预测嵌套病例对照研究中II型糖尿病（假设，第1部分）'<我们将评估经过培训的专家系统识别反映长期钙的血清型的能力。摄入量以确定来自1000个配对病例的血清中未来II型糖尿病的相对风险和来自特征良好的人群的对照（护士健康研究）。 J， - 我的目标3是确定临界血清标记物的生化认同（假设，第2部分）。 '我。质谱法将用于鉴定临界蛋白质和小分子成分的指定代谢性血清型，这些型号表征了大鼠的DR和人类相对II型糖尿病风险