Influence of Insulin on BP Change During Adolescence

Cardiovascular Diseases, Diabetes Mellitus, Hypertension, Insulin Resistance, Obesity

To define the relation of insulin resistance during childhood and adolescence to the development of the insulin resistance syndrome in young adulthood.

BACKGROUND: The insulin resistance syndrome (IRS) is associated with a considerable increase in the risk of cardiovascular disease in adults. The disorder most likely is inherited to some degree with onset in childhood and early adolescence. The IRS is best defined by quantitative data from euglycemic insulin clamp studies. The investigators have developed a unique data base in children, and by continuing repeated studies and follow-up in early adulthood together with studies in parents and siblings this study should provide important insight into the occurrence and progression of cardiovascular disease in later life. DESIGN NARRATIVE: The study is designed to: 1) define the relation of insulin resistance during childhood and adolescence to the development of insulin resistance syndrome (hypertension, dyslipidemia, obesity, and insulin resistance) in young adulthood; and 2) define the relation of insulin resistance within families. The original cohort consists of 357 children who have had two euglycemic insulin clamp studies (at mean ages 13 and 15 years). The specific aims are: to (1) repeat anthropometric and blood pressure measurements at mean ages 18, 19, and 20 and obtain insulin clamps, lipid levels, echocardiograms, and DEXA at mean age 21 in the children; and (2) obtain the measurements, blood and DNA samples, echocardiogram, and insulin clamp in the parents and siblings of the children. Statistical genetics methods are used to estimate heritability and genetic correlations among the insulin resistance syndrome traits. These data address the hypotheses that 1) insulin resistance in childhood predicts insulin resistance and cardiovascular risk factors in young adulthood; 2) insulin resistance in parents is associated with insulin resistance and cardiovascular risk factors in their children; 3) in fat children, BMI and insulin resistance at mean age 13 predicts cardiovascular risk, but in thin children only insulin resistance is a similar predictor; 4) insulin resistance has significant heritability; and 5) there are significant genetic correlations between insulin resistance and the insulin resistance traits. At least 300 of the original cohort of 357 who have had two euglycemic insulin clamps continue on in the study. The study continues through July, 2008.

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