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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL052851-12
Application #
7092298
Study Section
Epidemiology of Chronic Diseases Study Section (ECD)
Program Officer
Fabsitz, Richard
Project Start
1995-05-05
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
12
Fiscal Year
2006
Total Cost
$662,595
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang et al. (2015) Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene. J Clin Invest 125:1739-51
Bosch, Tyler A; Steinberger, Julia; Sinaiko, Alan R et al. (2015) Identification of sex-specific thresholds for accumulation of visceral adipose tissue in adults. Obesity (Silver Spring) 23:375-82
Frohnert, Brigitte I; Jacobs Jr, David R; Steinberger, Julia et al. (2013) Relation between serum free fatty acids and adiposity, insulin resistance, and cardiovascular risk factors from adolescence to adulthood. Diabetes 62:3163-9
Oikonen, Mervi; Laitinen, Tomi T; Magnussen, Costan G et al. (2013) Ideal cardiovascular health in young adult populations from the United States, Finland, and Australia and its association with cIMT: the International Childhood Cardiovascular Cohort Consortium. J Am Heart Assoc 2:e000244
Ognjanovic, S; Jacobs, D R; Steinberger, J et al. (2013) Relation of chemokines to BMI and insulin resistance at ages 18-21. Int J Obes (Lond) 37:420-3
Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A et al. (2013) Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes. Diabetes 62:3589-98
Dwyer, Terence; Sun, Cong; Magnussen, Costan G et al. (2013) Cohort Profile: the international childhood cardiovascular cohort (i3C) consortium. Int J Epidemiol 42:86-96
Polgreen, Lynda E; Jacobs Jr, David R; Nathan, Brandon M et al. (2012) Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity (Silver Spring) 20:2194-201
Rasmussen-Torvik, L J; Pankow, J S; Jacobs Jr, D R et al. (2012) Development of associations among central adiposity, adiponectin and insulin sensitivity from adolescence to young adulthood. Diabet Med 29:1153-8
Sinaiko, Alan R; Caprio, Sonia (2012) Insulin resistance. J Pediatr 161:11-5

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