Altered inflammatory, oxidative, and metabolic responses to exercise in pediatric obesity and type 1 diabetes

Abstract

Obesity (Ob) and type 1 diabetes (T1DM) are associated with increased inflammation and oxidative stress, which are major pathogenetic pathways toward higher cardiovascular risks. Although long-term exercise protects against systemic inflammation and oxidation, acute exercise actually exerts pro-inflammatory and oxidative effects, prompting the necessity for better defining these molecular processes in at-risk patients; in particular, very little is known regarding obese and T1DM children. We therefore examined key inflammatory and oxidative stress variables during exercise in 138 peripubertal children (47 Ob, 12.7 ± 0.4 yr, 22 F, BMI% 97.6 ± 0.2; 49 T1DM, 13.9 ± 0.2 yr, 20 F, body mass index% [BMI] 63.0 ± 3.6; 42 healthy, CL, 13.5 ± 0.5 yr, 24 F, BMI% 57.0 ± 3.6), who performed 10 bouts of 2-min cycling ~80% VO(2max) , separated by 1-min rest intervals. Blood samples were drawn at baseline and peak exercise. Ob displayed elevated baseline interleukin-6 (IL-6, 2.1 ± 0.2 pg/mL, p < 0.005) vs. CL (1.5 ± 0.3), whereas T1DM displayed the greatest maximum exercise-induced change in IL-6 (1.2 ± 0.3) than in both Ob (0.7 ± 0.1, p < 0.001) and CL (0.6 ± 0.1, p < 0.0167). Myeloperoxidase (MPO) was elevated in T1DM (143 ± 30 ng/mL, p < 0.0167) vs. CL (89 ± 10) and Ob (76 ± 6), whereas increases in exercise only occurred in Ob and CL. Disparate baseline and exercise responses were also observed for 8-hydroxy-2'-deoxyguanosine, glutathione, and F(2) -isoprostane. This data show distinct patterns of dysregulation in baseline and adaptive immunologic and oxidative responses to exercise in Ob and T1DM. A full understanding of these alterations is required so that developing exercise regimens aimed at maximizing health benefits for specific dysmetabolic states can be achieved based on complete scientific characterization rather than empirical implementation.

Fig. 1. Experimental design

All groups rested for 90 min in euglycemic range (T1DM required insulin/glucose infusions to achieve euglycemia prior to the 90 min period and euglycemic clamp throughout the remainder of the study). Exercise consisted of 2-min cycling at ~80% VO₂max followed by 1-min rest, completed 10 times. Blood samples were drawn before, during (at 18 min), peak-, and 30-min post-exercise. White bar, resting period; grey bar, cycling; large black arrow, blood draw for all analytes; small black arrow, additional small blood draws for quantification of IL-6.

Fig. 2. Plasma glucose, insulin, and lactate

Baseline glucose and insulin were higher in T1DM (black bar) and Ob (grey bar) than CL (white bar). Exercise-induced changes in plasma glucose and insulin in Ob and CL, but not T1DM. All groups had an increase in lactate due to exercise. Data are mean±SE. * (p<0.0167), T1DM and Ob vs. CL at baseline; ‡ (p<0.005), Ob vs. CL and T1DM at baseline; † (p<0.05), exercise-induced changes within groups; ** (p<0.0167), exercise-induced patterns T1DM vs. CL; *** (p<0.005), exercise-induced increase T1DM vs. Ob.

Fig. 3. Baseline and exercise-induced increases in IL-6

IL-6 was significantly elevated at baseline for Ob (grey circle) than CL (white circle), whereas T1DM (black circle) was intermediate. IL-6 increased significantly after exercise; IL-6 was higher in Ob than CL throughout the protocol, while T1DM displayed the greatest post exercise-induced change. Data are mean±SE. * (p<0.005), Ob vs. CL at baseline; † (p<0.005), exercise-induced increases within groups; ** (p<0.0167), exercise-induced patterns T1DM vs. CL and Ob.

Fig. 4. Altered levels of MPO and neutrophils in T1DM

Baseline MPO was significantly higher in T1DM (black bar) than CL (white bar) and Ob (grey bar), yet neutrophil counts were reduced compared to Ob. MPO increased following exercise in Ob and CL but not in T1DM, even when there was an increase in neutrophil counts for all 3 groups. Data are mean±SE. * (p<0.0167), T1DM vs. CL and Ob at baseline; ‡ (p<0.005), T1DM vs. Ob at baseline; † (p<0.005), exercise-induced increases within groups.

Fig. 5. Nitrotyrosine, 8-OHdG, and GSH-420

Baseline and peak exercise 8-OHdG was significantly lower in T1DM (black bar) and Ob (grey bar) than CL (white bar). GSH-420 was reduced in T1DM vs. CL and Ob. No exercise-induced changes occurred for these oxidative molecules in all groups. Data are mean±SE. * (p<0.005), T1DM and Ob vs. CL. † (p<0.005), T1DM vs. Ob and CL.

Fig. 6. Elevated baseline F₂-IsoP and FFA, and altered FFA response to exercise in Ob

Ob (grey bar) had elevated F₂-IsoP and FFA compared to CL (white bar) at baseline. FFA decreased in Ob, while glycerol increased for both groups at end-exercise. Data are mean±SE. * (p<0.005), Ob vs. CL at baseline; † (p<0.005), exercise-induced changes within each group; ** (p<0.05), exercise-induced patterns Ob vs. CL.