This study is designed to elucidate the interrelation and temporal appearance of precursors of metabolic syndrome (MS) in children and adolescents; the role of major epidemiological variables in the development of MS; and the relative contributions of environmental and genetic factors to attained level and longitudinal change in MS precursors. We propose a follow-up study of approximately 2000 twin pairs initially enrolled in 1998-2000 in Anqing, China, when the twins were aged 6-21 years. Available baseline information on the twins includes epidemiologic and dietary data, anthropometric measures (BMI; waist, hip circumferences, Tanner Stage), total and truncal adiposity assessed by dual energy X-ray absorptiometry (DEXA), blood pressure (BP), fasting lipids, fasting and 2-hr OGTT insulin and glucose, and zygosity.
Our specific aims are: (1) To conduct cross-sectional analyses using the existent baseline data in order to describe the distribution and interrelations of MS related phenotypes (anthropometric measures, adiposity, BP, lipids, insulin, glucose) across age, gender, and pubertal stages; examine the association of major epidemiological variables with MS phenotypes using conventional regression, co-twin analysis and multivariate methods; and estimate the heritability of MS phenotypes. (2) To follow up this cohort in order to re-measure all the MS related phenotypes using the same protocols standardized at baseline plus objective physical activity assessment by uniaxial accelerometer. (3) To conduct longitudinal analyses in order to describe the distributions of and interrelations among changes in MS phenotypes across age, gender, and pubertal stages; predict longitudinal changes in MS phenotypes (both as continuous and binary outcomes) using baseline levels and longitudinal changes of important epidemiological variables and MS markers; and estimate the heritability of longitudinal changes in MS phenotypes across age, gender, and pubertal stages. (4) To measure and assess promising but as yet unproven MS markers among MZ co-twins--insulin-like growth factor-1 (IGF-1), androgen, estrogen, testosterone, LH, and FSH; leptin, adiponectin; C-reactive protein (CRP), IL-6, TNF-alpha receptor 2; fibrinogen, factor VII, plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAl-1)-in order to explore cross-sectional and longitudinal correlations of these markers with established MS markers; and assess their utility as predictors of adverse progression in MS phenotypes. Our preliminary data show considerable variations in MS markers within this cohort, even though it is relatively lean. Further, % body fat in this cohort is almost linearly correlated with BP, triglycerides, fasting glucose and insulin without an evidence of threshold; and MS marker abnormality frequency increases markedly during puberty. This study will provide an in-depth cross-sectional and longitudinal investigation of both established and novel MS markers. Furthermore, this large twin cohort will better clarifv the eenetic versus environmental influences on the develooment of MS and its markers.
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