Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity.
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.
Nadeau
Kristen J
KJ
Division of Pediatric Endocrinology, The Children's Hospital, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. kristen.nadeau@ucdenver.edu
Zeitler
Phillip S
PS
Bauer
Timothy A
TA
Brown
Mark S
MS
Dorosz
Jennifer L
JL
Draznin
Boris
B
Reusch
Jane E B
JE
Regensteiner
Judith G
JG
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
D052242:Adiponectin; D015415:Biomarkers; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D008055:Lipids; D002097:C-Reactive Protein