Predictors of Youth-Onset Type 2 Diabetes: UAB Clinical Center

青年发病 2 型糖尿病的预测因子：UAB 临床中心

基本信息

批准号：
10582927
负责人：
Ambika Pallikunnath Ashraf
金额：
$ 5.81万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-10 至 2029-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10582927
关键词：
Accounting Adipose tissue Adult Affect African American population Age Alabama American Archives Beta Cell Body Composition Body fat Body mass index Carbohydrates Cell physiology Child Childhood Chronic stress Clinic Collaborations Data Deposition Diabetes Mellitus Diet Dietary Carbohydrates Dietary Sugars Dual-Energy X-Ray Absorptiometry Effectiveness Effectiveness of Interventions Endocrinology Environmental Risk Factor Ethnic Origin Etiology Evaluation Exhibits Family Family history of Fasting Fatty Liver Fatty acid glycerol esters Functional disorder Future Genes Genetic Genetic Materials Genetic Polymorphism Genetic Predisposition to Disease Genotype Glucose Hepatic Hispanic Americans Impaired fasting glycaemia Impairment Individual Insulin Insulin Resistance Intervention Intervention Studies Leg Lipids Liver Longitudinal cohort study Measures Metabolic Monitor Morbid Obesity Mutation Non-Insulin-Dependent Diabetes Mellitus Not Hispanic or Latino OGTT Obesity Outcome Measure Participant Pediatric Hospitals Peripheral Phenotype Physiological Physiology Plasma Prediabetes syndrome Predictive Factor Pregnancy Prevalence Probability Process Proinsulin Psychosocial Factor Publishing Race Recording of previous events Research Risk Risk Factors SNP genotyping Scanning Single Nucleotide Polymorphism Site Starch Technical Expertise Testing Tissue Expansion Universities Variant Visit Weight Gain Youth adverse childhood events aged clinical center cohort diabetes risk ethnic disparity glucose monitor glucose tolerance hospital care impaired glucose tolerance indexing insulin sensitivity intrauterine environment metabolomics minority children obesity risk pediatric patients predictive modeling progression risk racial disparity recruit response retention rate sex sugar

项目摘要

Minority youth are at elevated risk for type 2 diabetes (T2D) relative to non-Hispanic whites (NHW), with African-Americans (AA) and Hispanic-Americans (HA) showing the greatest increase in prevalence since 2000. Our overarching hypothesis is that underlying genetic differences in minority children interact with environmental factors in an adverse manner to increase risk for T2D. For example, the elevated beta-cell responsiveness and reduced hepatic insulin extraction exhibited by AA may increase risk for obesity and beta- cell dysfunction in the context of a diet high in sugar and processed starches. HA have both a genetic predisposition to fatty liver, due to a mutation in the carbohydrate-responsive PNPLA3 gene, and a genetic impairment in the ability to expand peripheral adipose tissue. In the context of weight gain and a high- sugar/processed carbohydrate diet, these genetic factors may increase risk for insulin resistance. The global purpose of RFA-DK-21-002 is to identify factors that predict conversion to T2D, and that disproportionately predispose minority youth to T2D. With our “University of Alabama at Birmingham (UAB) Clinical Center,” we propose to recruit, phenotype, and follow for 5 years 100 at-risk youth aged 8-16 yr without T2D at baseline comprised primarily of AA children with extreme obesity. Our team excels in assessment of insulin sensitivity and beta-cell function; assessment of body composition and body fat distribution; evaluation of the intrauterine environment; and conducting longitudinal cohort studies with high retention. Published data indicate that the greatest risk factors for pediatric T2D are extreme obesity (BMI z score > 2.5), impaired glucose tolerance (2-h glucose >140 mg/dL and <200 mg/dL), weight gain, and family or maternal/gestational history of diabetes. We will assess all of these variables with annual testing visits that will include an oral glucose tolerance test and dual-energy-X-ray absorptiometry (DXA) for body composition and fat distribution. In addition, we will collect genetic material for assessment of targeted SNPs with known association to T2D risk, and we will assess environmental factors such as psychosocial variables and diet. Sera/plasma will be archived for future metabolomics. Prediction models will be developed for incident T2D, as well as for prevalent and incident IGT, using suites of anthropometric/demographic, phenotypic, and genotypic variables. We hypothesize that ethnicity/race will not be statistically related to incident T2D when accounting for genotypic and/or phenotypic factors that affect risk for T2D, and their potential interaction with environmental factors. Results from this study will identify the genetic underpinnings of the phenotypic and anthropometric/familial factors that associate with, and reflect the pathophysiology of, IGT and T2D, and will determine whether these determinants differ with ethnicity/race. As such, the results of this study will identify targets for intervention, and markers for monitoring intervention effectiveness, that can be utilized in subsequent intervention studies.

相对于非西班牙裔白人（NHW），少数族裔青年患有2型糖尿病（T2D）的风险较高非裔美国人（AA）和西班牙裔美国人（HA）表现出自2000年以来患病率最大的增长。我们的总体假设是，少数族裔儿童的潜在遗传差异与环境因素以不利的方式增加T2D的风险。例如，高架β细胞反应性和减少AA暴露于AA暴露的肝胰岛素提取可能会增加肥胖和β- 细胞功能障碍在糖和加工恒星高的饮食中。 HA都有两个遗传由于碳水化合物反应性PNPLA3基因的突变，脂肪肝易感性扩展外周脂肪组织的能力受损。在体重增加和高度糖/加工碳水化合物饮食，这些遗传因素可能会增加胰岛素抵抗的风险。全球 RFA-DK-21-002的目的是确定预测转化为T2D的因素，并且不成比例容易少数族裔青年对T2D。我们的“阿拉巴马大学在伯明翰（UAB）临床中心” 提议招募，表型和遵循5年的100年危险年轻人，年龄8 - 16岁，没有T2D。主要由AA极端肥胖的儿童汇编。我们的团队评估胰岛素敏感性的例外和β细胞功能；评估人体成分和体内脂肪分布；内存的评估环境;并进行高保留率的纵向队列研究。已发布的数据表明小儿T2D的最大危险因素是极端肥胖（BMI Z评分> 2.5），葡萄糖耐受性受损（2-H 葡萄糖> 140 mg/dl和<200 mg/dl），体重增加以及糖尿病的家族或孕育病史。我们将通过年度测试访问评估所有这些变量，其中包括口服葡萄糖耐量测试和双能X射线绝对肽（DXA）用于人体组成和脂肪分布。此外，我们将收集用于评估具有已知关联与T2D风险的靶向SNP的遗传材料，我们将评估环境因素，例如社会心理变量和饮食。血清/等离子体将存档以备未来代谢组学。将针对事件T2D以及普遍和事件IGT开发预测模型，使用人体测量/人口统计学，表型和基因型变量的套件。我们假设这一点考虑基因型和/或表型时，种族/种族在统计上与事件T2D无关影响T2D风险的因素及其与环境因素的潜在相互作用。结果研究将确定表型和人体测量/家族因素的遗传基础与IGT和T2D的病理生理相关联，并将确定是否确定种族/种族不同。因此，这项研究的结果将确定干预目标，以及用于监测干预效果的标记，可以在随后的干预研究中使用。