This research application is a continuation of a project initiated in 1995 to study insulin resistance in children. The primary objectives are (1) to define the relation of insulin resistance (defined by the euglycemic insulin clamp) during childhood and adolescence to the development of the insulin resistance syndrome (i.e., hypertension, dyslipidemia, obesity, and insulin resistance) in young adulthood; and (2) to define the relation of the insulin resistance syndrome within families and the importance of genetics to that relation. 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 will be used to estimate heritability and genetic correlations among the insulin resistance syndrome traits. These data will address the hypotheses that 1) insulin resistance in childhood will predict insulin resistance and cardiovascular risk factors in young adulthood; 2) insulin resistance in parents will be associated with insulin resistance and cardiovascular risk factors in their children; 3) in fat children, BMI and insulin resistance at mean age 13 will predict cardiovascular risk, but in thin children only insulin resistance will be a similar predictor; 4) insulin resistance has significant heritability; and 5) there are significant genetic correlations between insulin resistance and the insulin resistance traits. It is anticipated that at least 300 of the original cohort of 357 who have had two euglycemic insulin clamps will complete the five years of this continuation. The investigators state that the significance of this project lies in its potential to define the factors influencing development of the insulin resistance syndrome and provide the basic clinical data required to begin to study genetic patterns of cardiovascular disease.
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