title: Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity.
abstract: BACKGROUND
  The incidence of pediatric type 2 diabetes (T2D) is rising, with unclear effects on the cardiovascular system. Cardiopulmonary fitness, a marker of morbidity and mortality, is abnormal in adults with T2D, yet the mechanisms are incompletely understood.
  
  
  OBJECTIVE
  We hypothesized that cardiopulmonary fitness would be reduced in youth with T2D in association with insulin resistance (IR) and cardiovascular dysfunction.
  
  
  METHODS
  We conducted a cross-sectional study at an academic hospital that included 14 adolescents (age range, 12-19 yr) with T2D, 13 equally obese adolescents and 12 lean adolescents similar in age, pubertal stage, and activity level.
  
  
  METHODS
  Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, body composition by dual-energy x-ray absorptiometry, intramyocellular lipid by magnetic resonance spectroscopy, and inflammation by serum markers.
  
  
  RESULTS
  Adolescents with T2D had significantly decreased VO(2)peak and insulin sensitivity, and increased soleus intramyocellular lipid, C-reactive protein, and IL-6 compared to obese or lean adolescents. Adolescents with T2D also had significantly prolonged VO(2)kinetics, decreased work rate, vascular reactivity, and adiponectin, and increased left ventricular mass and fatty acids compared to lean adolescents. In multivariate linear regression analysis, IR primarily, and fasting free fatty acids and forearm blood flow secondarily, were significant independent predictors of VO(2)peak.
  
  
  CONCLUSIONS
  Given the strong relationship between decreased cardiopulmonary fitness and increased mortality, these findings in children are especially concerning and represent early signs of impaired cardiac function.
authors: Division of Pediatric Endocrinology, The Children's Hospital, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. kristen.nadeau@ucdenver.edu
authors: Kristen J
authors: KJ
authors: Nadeau
authors: Phillip S
authors: PS
authors: Zeitler
authors: Timothy A
authors: TA
authors: Bauer
authors: Mark S
authors: MS
authors: Brown
authors: Jennifer L
authors: JL
authors: Dorosz
authors: Boris
authors: B
authors: Draznin
authors: Jane E B
authors: JE
authors: Reusch
authors: Judith G
authors: JG
authors: Regensteiner
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001823:Body Composition; D050218:Body Fat Distribution; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D004452:Echocardiography; D005080:Exercise Test; D017079:Exercise Tolerance; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006339:Heart Rate; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008297:Male; D009043:Motor Activity; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010101:Oxygen Consumption; D010991:Plethysmography; D011627:Puberty; D013851:Thinness; D055815:Young Adult
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D008055:Lipids; D002097:C-Reactive Protein