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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #338655
Title: Endothelial function in youth: A biomarker modulated by adiposity-related insulin resistance

Author
item TOMSA, ANCA - Texas Children'S Hospital
item BARTZ, SARA - Texas Children'S Hospital
item KRISHNAMURTHY, RAJESH - Texas Children'S Hospital
item KRISHNAMURTHY, RAMKUMAR - Texas Children'S Hospital
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/13/2016
Publication Date: 11/1/2016
Citation: Tomsa, A., Bartz, S.K., Krishnamurthy, R., Krishnamurthy, R., Bacha, F. 2016. Endothelial function in youth: A biomarker modulated by adiposity-related insulin resistance. Journal of Pediatrics. 178:171-177.

Interpretive Summary: Endothelial dysfunction is an early marker of subclinical atherosclerosis and can be measured non-invasively by measuring the blood flow characteristics in the small vessels of the fingers. We utilized this method to understand whether there is evidence of early changes in endothelial function in youth with obesity and type 2 diabetes and what drives this early abnormality. Youth underwent an evaluation of endothelial function. We found impairment in endothelial function in youth in relation to total body fat and abdominal fat, and evidence of greater stiffness of the blood vessels. The adverse effects of body fatness on these measures were related to insulin resistance and markers of inflammation. Therefore, we showed that childhood obesity is associated with early subclinical vessel dysfunction. Insulin resistance appears to explain the effect of obesity on the early vascular abnormality in youth.

Technical Abstract: To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with normal glucose tolerance, 19 overweight with impaired glucose regulation, and 16 with type 2 diabetes mellitus underwent evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) at heart rate 75 bpm by peripheral arterial tonometry; oral glucose tolerance test, lipid profile, and hyperinsulinemic-euglycemic clamp to measure insulin sensitivity; and dual energy X-ray absorptiometry scan and abdominal magnetic resonance imaging for percentage of body fat and abdominal fat partitioning. Participants across tertiles of RHI (1.2+/-0.02, 1.5+/-0.02, and 2.0+/-0.05, P<.001) had similar age, sex, race, lipid profile, and blood pressure. Body mass index z-score, percentage body fat, abdominal fat, and hemoglobin A1c decreased, and insulin sensitivity increased from the first to third tertile. RHI was inversely related to percentage body fat (r=-0.29, P=.008), total (r=-0.37, P=.004), subcutaneous (r=-0.39, P=.003), and visceral (r=-0.26, P=.04) abdominal fat. AIx at heart rate 75bpm was higher (worse) in the lower RHI tertiles (P=.04), was positively related to percentage body fat (r=0.26, P=.021), and inversely related to age, insulin sensitivity, and inflammatory markers (tumor necrosis factor-alpha and plasminogen activator inhibition-1). Childhood obesity, particularly abdominal adiposity, is associated with endothelial dysfunction manifested by worse reactive hyperemia and higher AIx. Insulin resistance appears to mediate this relationship.