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

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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.