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

描述（由申请人提供）：相似体重指数（BMI）的个体在心脏代谢风险（即血压升高，甘油三酯升高，HDL-C降低，葡萄糖升高，胰岛素抵抗和全身炎症）方面表现出可变性，导致“代谢健康-超重”表型，以及“代谢危险-正常体重”表型。在快速现代化的国家，如中国，我们对这些表型知之甚少，这些国家在过去二十年中经历了肥胖、胰岛素抵抗、2型糖尿病和心血管疾病的急剧出现。这项拟议的研究利用了来自美国国立卫生研究院资助的中国健康与营养调查（CHNS）的约9,000名参与者的20年纵向数据，以检查儿童、青少年、青年和中年人中“代谢健康-超重”和“代谢危险-正常体重”表型的肥胖和中心性肥胖的时间和持续时间如何在当前心脏代谢风险中形成变异性。特别令人感兴趣的是按体重状况、性别、年龄和城市化程度划分的心脏代谢风险因素，这将有助于了解城市化带来的快速环境变化背景下的风险进展。中国在回答这些问题方面具有独特的优势，因为在相对较低的BMI和较年轻的人群中，心脏代谢危险因素的患病率很高，而且亚洲人的腹部肥胖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作为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的纵向测量。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、性别和城市划分体重状况，确定心脏代谢风险（收缩压和舒张压升高、糖化血红蛋白、葡萄糖、胰岛素、CRP、甘油三酯和HDL-C降低）；2)确定(a)体重史（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)这种关系是否因体重增加最大的年龄而异。使用潜在类别分析，我们将描述体重史的模式，并将所得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影响不同年龄经历快速环境变化的人群的心脏代谢风险。本研究的结果将适用于中国以外的地区，以更好地了解“代谢健康-超重”和“代谢危险-正常体重”表型中心脏代谢风险的异质性。

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.