Heterogeneity in Cardiometabolic Risk with Obesity: Who Is at Risk?

描述(申请人提供)：体重指数(BMI)相似的个体表现出心脏代谢风险的变异性(即血压升高、甘油三酯升高、高密度脂蛋白降低、血糖升高、胰岛素抵抗和全身炎症)，导致“代谢健康-超重”的表型，以及“代谢危险-正常体重”的表型。在中国这样的快速现代化国家中，我们对这些表型知之甚少，在过去20年里，随着城市化的发展，这些国家经历了肥胖、胰岛素抵抗、2型糖尿病和心血管疾病的戏剧性出现。这项拟议的研究利用美国国立卫生研究院资助的中国健康与营养调查(CHNS)中约9,000人20年的纵向数据，研究肥胖的发生时间和持续时间以及中心性肥胖的形状变异在当前心脏代谢风险中是如何影响儿童、青少年、青年和中年人的“代谢健康-超重”和“代谢高危-正常体重”表型的。特别令人感兴趣的是按体重状况以及跨性别、年龄和城市化程度划分的心脏代谢危险因素星座，这将有助于理解随着城市化发生的快速环境变化背景下风险的进展。中国在回答这些问题上处于独特的地位，因为心脏代谢危险因素在相对较低的BMI和较年轻的年龄段很高，而且亚洲人的腹型肥胖率和胰岛素抵抗率相对较高。我们利用新收集的空腹血液样本来检测心脏代谢生物标志物，以及大量先前的人体测量、血压和详细的行为、社会经济和环境信息。我们的目标包括：1)在考虑腹部脂肪分布的差异后，根据年龄、性别和都市性来表征不同体重状态下的心脏代谢风险(SBP和DBP升高、HbA1c、血糖、胰岛素、CRP、甘油三酯和降低的高密度脂蛋白胆固醇)；以及2)确定(A)体重病史(体重增加的时间、持续时间和速度)与心脏代谢风险的关系，以及(B)这些关系是否因体重增加最大的年龄而不同。使用潜在类别分析，我们将表征体重病史的模式，并将结果类别用作心脏代谢风险模型中的暴露变量。这项研究的发现将进一步了解体重史如何在不同年龄经历快速环境变化的队列中构成心脏代谢风险的基础。这项研究的发现将适用于中国以外的人群，以更好地了解“代谢健康-超重”和“代谢高危-正常体重”表型中体重状态对心脏代谢风险的异质性。 与公共卫生相关：中国是一个快速现代化的国家，面临着糖尿病和心血管疾病的沉重负担。拟议研究的目的是了解年龄、性别和都市性的变异性在多大程度上影响心脏代谢风险。这项拟议的研究将为减轻体重状况下疾病风险早期发展的努力提供信息。

DESCRIPTION (provided by applicant): Individuals of similar body mass index (BMI) exhibit variability in cardiometabolic risk (i.e., elevated blood pressure, elevated triglycerides, decreased HDL-C, elevated glucose, insulin resistance, and systemic inflammation), resulting in the "metabolically healthy - overweight" phenotype, as well as the "metabolically at risk - normal weight" phenotype. We know very little of these phenotypes in the context of rapidly modernizing countries such as China that have experienced dramatic emergence of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease occurring with urbanization over the past two decades. The proposed study takes advantage of 20-year longitudinal data from approximately 9,000 individuals enrolled in the NIH- funded China Health and Nutrition Survey (CHNS), to examine how the timing and duration of obesity and central adiposity shape variability in current cardiometabolic risk underlying the "metabolically healthy - overweight" and the "metabolically at risk - normal weight" phenotypes in children, adolescents, young- and middle-aged adults. Of particular interest is the constellation of cardiometabolic risk factors by weight status and across sex, age, and urbanicity, which will inform understanding of the progression of risk in the context of rapid environmental change occurring with urbanization. China is uniquely positioned to answer these questions due to high prevalence of cardiometabolic risk factors at relatively low BMI and at younger ages, and given relatively higher abdominal obesity and high rates of insulin resistance in Asians. We capitalize on newly collected fasting blood samples for cardiometabolic biomarkers as well as a vast array of prior longitudinal measures of anthropometry, blood pressure, and detailed behavioral, socioeconomic and environmental information. Our objectives include: 1) Characterize cardiometabolic risk (elevated SBP and DBP, HbA1c, glucose, insulin, CRP, triglycerides, and decreased HDL-C) across weight status by age, sex, and urbanicity after accounting for differences in abdominal fat distribution; and 2) Determine (a) how weight history (timing, duration, and rapidity of weight gain) relates to cardiometabolic risk, and (b) whether such relationships differ by age at greatest weight gain. Using latent class analysis, we will characterize patterns of weight history, and use the resulting classes as exposure variables in models of cardiometabolic risk. Findings from this study will further understanding of how weight history underlies cardiometabolic risk across cohorts experiencing rapid environmental change at different ages. Findings from this study will apply beyond China to provide a better understanding of the heterogeneity of cardiometabolic risk by weight status in the "metabolically healthy - overweight" and "metabolically at risk - normal weight" phenotypes. PUBLIC HEALTH RELEVANCE: China is a rapidly modernizing country experiencing substantial burden in diabetes and cardiovascular disease. The objective of the proposed research is to understand the extent to which variability in age, sex, and urbanicity shape cardiometabolic risk. The proposed research will inform efforts to mitigate early development of disease risk across weight status.