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

Abstract

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.

Figures

Figure 1

Maximal exercise capacity (VO2peak) in control (white bar), obese (hatched bar), and T2D (black bar) adolescents, expressed in milliliters per kilogram per minute. *, P values compared to control adolescents; †, P values compared to obese adolescents.

Figure 2

Correlation between maximal exercise capacity (VO2peak) expressed in milliliters per kilogram per minute and glucose disposal rate from the hyperinsulinemic euglycemic clamp, expressed in milligrams per kilogram per minute. •, Control males; ○, control females; ▪, obese males; □, obese females; ▴, T2D males; ▵, T2D females.

Figure 3

A, Correlation between maximal exercise capacity (VO2peak) expressed in milliliters per kilogram per minute and peak hyperemic forearm blood flow from venous plethysmography, expressed in milliliters per 100 ml per minute. B, Correlation between maximal exercise capacity (VO2peak) expressed in milliliters per kilogram per minute and fasting FFA, expressed in microequivalents per liter. •, Control males; ○, control females; ▪, obese males; □, obese females; ▴, T2D males; ▵, T2D females.