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Insulin Resistance in Adolescents with Type 2 Diabetes Is Associated with Impaired Exercise Capacity

Division of Pediatric Endocrinology (K.J.N., P.S.Z.), The Children’s Hospital, University of Colorado Denver School of Medicine; Divisions of General Internal Medicine (T.A.B.), Radiology (M.S.B.), Cardiology (J.L.D.), and Endocrinology (B.D.), University of Colorado Denver School of Medicine; Division of Endocrinology (J.E.B.R.), Veterans Administration Hospital, University of Colorado Denver School of Medicine; and Division of Cardiology (J.G.R.), Center for Women’s Health Research, University of Colorado Denver School of Medicine, Aurora, Colorado 80045

Address all correspondence and requests for reprints to: Kristen J. Nadeau, M.D., Assistant Professor of Pediatrics, University of Colorado Health Sciences Center, The Children’s Hospital, Department of Pediatric Endocrinology B265, 13123 East 16th Avenue, Aurora, Colorado 80045. E-mail: kristen.nadeau{at}ucdenver.edu.

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 (VO₂peak) and oxygen uptake kinetics (VO₂kinetics), 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 VO₂peak 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 VO₂kinetics, 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 VO₂peak.

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.