Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity

J Clin Endocrinol Metab. 2009 Oct;94(10):3687-95. doi: 10.1210/jc.2008-2844. Epub 2009 Jul 7.


Context: 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.

Design, setting, and participants: 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.

Main outcome measures: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adiponectin / blood
  • Adolescent
  • Biomarkers / blood
  • Blood Flow Velocity
  • Blood Pressure
  • Body Composition
  • Body Fat Distribution
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Child
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Echocardiography
  • Exercise Test
  • Exercise Tolerance*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Heart Rate
  • Humans
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / physiopathology
  • Inflammation / blood
  • Insulin Resistance*
  • Interleukin-6 / blood
  • Linear Models
  • Lipids / blood
  • Male
  • Motor Activity
  • Obesity / metabolism
  • Obesity / physiopathology
  • Oxygen Consumption
  • Plethysmography
  • Puberty
  • Thinness
  • Young Adult


  • Adiponectin
  • Biomarkers
  • Fatty Acids, Nonesterified
  • Interleukin-6
  • Lipids
  • C-Reactive Protein