The objective of the study is to predict the insulin resistance syndrome (IRS) and cardiovascular risk in adulthood from measures of fatness and insulin resistance in childhood and adolescence. Potentially mediating factors and subclinical cardiovascular disease also will be evaluated.
The specific aims are: 1) to measure insulin resistance (euglycemic insulin clamp); serum insulin, glucose, and lipids; to obtain anthropometric and blood pressure measurements; to obtain DEXA and a single slice CT abdominal scan; to complete questionnaires (medical history, physical activity, and diet); and to measure subclinical cardiovascular disease (carotid artery intima-media thickness, brachial artery endothelial reactivity and electrocardiograms) at age 22 in a cohort of 300 participants and their siblings; 2) to obtain an abdominal CT and cardiovascular studies in their parents; and 3) to measure free fatty acids, 8-iso-PGF2a, cytokines and CRP in the children and parents. This data will address the hypotheses that 1) insulin resistance in conjunction with fatness in adolescence are more predictive of the IRS and subclinical cardiovascular changes in young adulthood than is fatness alone; 2) expression of the IRS during adolescence will predict subclinical cardiovascular changes in young adulthood and will be associated with the IRS and subclinical cardiovascular disease in their parents; 3) fatty acid composition in diet, cholesterol esters and phospholipids is related to fatness and insulin resistance in adolescence and young adulthood in the same pattern as reported in adults with atherosclerotic cardiovascular disease and IRS; 4) intake of a Mediterranean-style diet predicts less body fatness, insulin resistance and subclinical cardiovascular change, but intake of a Western diet has the opposite effect; and 5) visceral adiposity in young adulthood is associated with expression of the IRS independent of overall body fatness. The significance of this research is in its potential to identify the temporal interactions operative in establishing the IRS. It can improve the health of the population by providing the scientific information required to develop prevention and intervention strategies that can be applied prior to establishment of the disease process.
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