Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function.
BACKGROUND
Cardiovascular disease is the major cause of death in adults with diabetes, yet little is specifically known about the effects of type 1 diabetes (T1D) on cardiovascular outcomes in youth. Although insulin resistance (IR) likely contributes to exercise and cardiovascular dysfunction in T2D, IR is not typically considered a contributor in T1D.


OBJECTIVE
We hypothesized that cardiopulmonary fitness would be reduced in T1D youth in association with IR and cardiovascular dysfunction.


METHODS
This cross-sectional study at an academic hospital included 12 T1D adolescents compared with 12 nondiabetic controls, similar in age, pubertal stage, activity level, and body mass index.


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, intramyocellular lipid by magnetic resonance spectroscopy, and body composition by dual-energy x-ray absorptiometry.


RESULTS
T1D adolescents had significantly decreased VO(2)peak, peak work rate, and insulin sensitivity compared with nondiabetic adolescents. T1D youth also had reduced vascular reactivity and evidence of diastolic dysfunction and left ventricular hypertrophy. Despite their IR and reduced cardiovascular fitness, T1D youth had paradoxically normal intramyocellular lipid, waist to hip ratio, and serum lipids and high adiponectin levels. In multivariate analysis, IR primarily, and forearm blood flow secondarily, independently predicted VO(2)peak.


CONCLUSIONS
T1D youth demonstrated IR, impaired functional exercise capacity and cardiovascular dysfunction. The phenotype of IR in T1D youth was unique, suggesting a pathophysiology that is different from T2D, yet may adversely affect long-term cardiovascular outcomes.
Nadeau
Kristen J
KJ
AssistantUniversity of Colorado Health Sciences Center, The Children's Hospital, Department of Pediatric Endocrinology B265, 13123 East 16th Avenue, Aurora, Colorado 80045, USA. kristen.nadeau@ucdenver.edu
Regensteiner
Judith G
JG
Bauer
Timothy A
TA
Brown
Mark S
MS
Dorosz
Jennifer L
JL
Hull
Amber
A
Zeitler
Phil
P
Draznin
Boris
B
Reusch
Jane E B
JE
D000293:Adolescent; D001823:Body Composition; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D010101:Oxygen Consumption
D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human