Metabolic Pathways in Carbohydrate Digestion-Related Amylase Variation and Type 2 Diabetes

碳水化合物消化相关淀粉酶变异和 2 型糖尿病的代谢途径

• 批准号: 10504815
• 负责人: Yoriko Heianza
• 金额: $ 25.47万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-10 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10504815
• 关键词: Advanced Development; Amylases; Baseline Surveys; Biological Markers; Black race; Blood Glucose; Carbohydrates; Cardiometabolic Disease; Centers of Research Excellence; Clinical Research; Communication; Complex; Consensus; Copy Number Polymorphism; DNA; Data; Diet; Dietary Carbohydrates; Dietary intake; Digestion; Disease; Distant; Endocrine; Energy Intake; Energy-Generating Resources; Ensure; Enzymes; Exhibits; Fasting; Funding; Genes; Genetic; Genomics; Genotype; Glucose; Glycosylated hemoglobin A; Goals; Heart; Hormones; Hyperglycemia; Impairment; Individual Differences; Insulin Resistance; Intake; Interdisciplinary Study; Lead; Life; Life Style Modification; Link; Louisiana; Macronutrients Nutrition; Measures; Mediating; Mediator of activation protein; Metabolic; Metabolic Pathway; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Outcome; Pancreas; Paper; Participant; Pathway interactions; Patients; Plasma; Play; Prediabetes syndrome; Preventive; Publishing; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Role; Salivary; Sample Size; Sampling; Starch; Surveys; Testing; Therapeutic; Time; Translational Research; United States; Variant; Woman; biracial; blood glucose regulation; carbohydrate metabolism; dietary starch; digital; disorder risk; epidemiology study; experience; fasting glucose; fibroblast growth factor 21; follow-up; global health; glucose metabolism; insight; insulin secretion; men; metabolomics; novel; programs; prospective

PROJECT SUMMARY Type 2 diabetes (T2D) is a global health issue causing a variety of life-threatening complications. Carbohydrates are the primary energy source and have substantial effects on blood glucose and insulin secretion. There is widespread consensus that the quantity and quality of carbohydrates play a pivotal role in controlling glucose metabolism and determining risks of T2D and impaired glucose metabolism. However, complex associations of carbohydrates with glucose metabolism may exist, partly attributable to genetic adaptation to starch (carbohydrate)-rich diets. Salivary and pancreatic amylases (encoded by amylase genes AMY1 and AMY2) are responsible for carbohydrate/starch digestion. The AMY genes exhibit copy number variations (CNVs), leading to individual differences in the amount and activity of amylase enzymes. The overarching goal of this project is to prospectively investigate interrelations between the carbohydrate-digestion determining AMY CNVs, dietary intakes of carbohydrates and starch (both quantity and quality), and longitudinal changes in glucose metabolism and risks of incident hyperglycemia and T2D. The Bogalusa Heart Study is an ongoing epidemiological study among a biracial sample (35% Black and 65% White) of men and women in Bogalusa, Louisiana, a state with the highest burden of obesity and T2D in the United States. The AMY1-AMY2 CNVs will be measured by a novel droplet digital PCR approach in 1250 participants of the Bogalusa Heart Study. This project examines associations of AMY1-AMY2 CNVs with subsequent changes in markers of glucose metabolism (fasting glucose, hemoglobin A1c, fasting insulin, and insulin resistance) and the risks of incident hyperglycemia and T2D over 7- 9 years. This project investigates whether the AMY CNVs influence the outcomes through mediating effects on plasma enzymatic levels of AMY1 and AMY2. Also, prospective gene-diet interactions analyses will be performed to test whether dietary intakes of carbohydrate and starch (both quantity and quality) significantly modify the relations between the AMY CNVs and the outcomes. This project also utilizes circulating metabolomic signatures covering a broad range of carbohydrate/glucose metabolism pathways and a carbohydrate-intake-related hormone, fibroblast growth factor 21, as mediators to test whether these biomarkers mediate the relations between the AMY CNVs and the outcomes. The findings of this project would lead to the identification of new risk factors for impaired glucose metabolism and T2D and advance the development of novel preventive and therapeutic strategies. The COBRE support will help the Research Project Leader acquire experience leading a multidisciplinary research project, publishing high-quality research papers, and obtaining pilot data for applying for R01 funding and transitioning into a competitive independent investigator.

项目摘要 2型糖尿病（T2 D）是一个全球性的健康问题，导致各种危及生命的并发症。碳水化合 是主要的能量来源，并对血糖和胰岛素分泌有实质性的影响。有 广泛的共识是碳水化合物的数量和质量在控制葡萄糖中起着关键作用 代谢和确定T2 D和糖代谢受损的风险。然而， 糖代谢的碳水化合物可能存在，部分原因是遗传适应淀粉 （碳水化合物）丰富的饮食。唾液和胰腺淀粉酶（由淀粉酶基因AMY 1和AMY 2编码）是 负责碳水化合物/淀粉消化。AMY基因表现出拷贝数变异（CNVs），导致 淀粉酶的量和活性的个体差异。本项目的总体目标是 前瞻性研究碳水化合物消化决定AMY CNVs，饮食 碳水化合物和淀粉的摄入量（数量和质量），以及葡萄糖代谢的纵向变化 以及高血糖症和T2 D的风险。博加卢萨心脏研究是一项正在进行的流行病学研究 在路易斯安那州的博加卢萨，一个有着35%黑人和65%白色的州， 肥胖和T2 D的最高负担。AMY 1-AMY 2 CNV将通过一种新的 在博加卢萨心脏研究的1250名参与者中使用液滴数字PCR方法。本项目研究 AMY 1-AMY 2CNV与葡萄糖代谢标志物（空腹血糖， 血红蛋白A1 c、空腹胰岛素和胰岛素抵抗）以及7- 10岁以上发生高血糖症和T2 D的风险。 9年本项目研究AMY CNVs是否通过介导 血浆酶水平的AMY 1和AMY 2。此外，还将进行前瞻性基因-饮食相互作用分析 为了测试饮食中碳水化合物和淀粉的摄入量（数量和质量）是否显著改变了 AMY CNV与结果之间的关系。该项目还利用循环代谢组学签名 涵盖了广泛的碳水化合物/葡萄糖代谢途径和碳水化合物摄入相关的 激素，成纤维细胞生长因子21，作为介质，以测试这些生物标志物是否介导的关系， AMY CNV和结果之间的关系。该项目的研究结果将导致确定新的 糖代谢受损和2型糖尿病的危险因素，并推进新的预防和 治疗策略COBRE支持将帮助研究项目负责人获得领导 多学科研究项目，发表高质量的研究论文，并获得应用的试点数据 R 01资金和过渡到一个有竞争力的独立调查员。