title: Endothelial Function in Youth: A Biomarker Modulated by Adiposity-Related Insulin Resistance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 75 bpm 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-α and plasminogen activator inhibition-1).
  
  
  CONCLUSIONS
  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.
authors.affiliation: US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Endocrinology and Diabetes, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
authors.forename: Anca
authors.initials: A
authors.lastname: Tomsa
authors.affiliation: US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Endocrinology and Diabetes, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
authors.forename: Sara
authors.initials: S
authors.lastname: Klinepeter Bartz
authors.affiliation: Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Krishnamurthy
authors.affiliation: Department of Radiology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Krishnamurthy
authors.affiliation: US Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX; Division of Pediatric Endocrinology and Diabetes, Texas Children's Hospital, Baylor College of Medicine, Houston, TX. Electronic address: fbacha@bcm.edu.
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
mesh_terms: D000273:Adipose Tissue; D050154:Adiposity / Q000502:physiology*; D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D004727:Endothelium / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D050177:Overweight / Q000150:complications / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: endothelial function; inflammatory markers; insulin resistance