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Diet plays an important role in modulating exercise responses, including activation of the growth hormone (GH)/insulin-like growth factor-I (IGF-1) axis. Obesity and fat ingestion were separately shown to reduce exercise GH responses, but their combined effect, especially important in children, has not been studied. We therefore measured the GH response to exercise [30-min intermittent cycling, ten 2-min bouts at ∼80% maximal aerobic capacity (V̇o2max), separated by 1-min rest], started 45 min after ingestion of a high-fat meal (HFM) in 16 healthy [controls; body mass index percentile (BMI%ile) 51 ± 7], and 19 obese (Ob, BMI%ile 97 ± 0.4) children. Samples were drawn at baseline (premeal), and at start, peak, and 30 min postexercise. In the Ob group, a marked ∼75% suppression of the GH response (ng/ml) to exercise was observed (2.4 ± 0.6 vs. 10.6 ± 2.1, P < 0.001). This level of suppression was also significantly greater compared with age-, fitness-, and BMI-matched historical controls that had performed identical exercise in fasting conditions. Our data indicate that the reduction in the GH response to exercise, already present in obese children vs. healthy controls, is considerably amplified by ingestion of fat nutrients shortly before exercise, implying a potentially downstream negative impact on growth factor homeostasis and long-term modulation of physiological growth.

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.

Modulation of inflammatory status is considered a key component of the overall health effects of exercise. This may be especially relevant in children with obesity (Ob) or type 1 diabetes (T1DM), in which an imbalance between pro- and anti-inflammatory mediators could accelerate onset and progression of cardiovascular complications. To date, exercise-induced alterations in immuno-modulatory mediators in Ob and T1DM children remain largely unknown.In this study, we monitored the kinetic profiles of 8 pro-and anti-inflammatory cytokines (TNF-a, IL-6, IL-2, IL-8, IL-5, IL-13, IL-10, IL-4) during a standardized exercise challenge (ten 2-min cycling bouts at 80% VO2max, separated by 1-min intervals) in 23 Ob (12 females, 11 males), 23 T1DM (10 females and 13 males) patients and 20 healthy (CL, 10 females and 10 males) children. Blood glucose of T1DM patients was kept in the 4.4-6.1 mM range for at least 90 minute prior to and during exercise. Blood samples were drawn at rest and after every other exercise bout.In Ob, TNF-a and IL-2 were significantly greater (p

Leukocytosis contributes to exercise-induced immune modulation, which is a mechanism of cardiovascular protection. However, this process is poorly defined in children. We therefore measured leukocytes in 45 healthy, 18 overweight, 16 type 1 diabetic, and 8 asthmatic children at pre, end-, and 30-min postexercise (30-min intermittent or 6-min continuous). In all groups, total leukocytes, neutrophils, lymphocytes, and monocytes increased at end-exercise, but returned to baseline by 30-min postexercise, including neutrophils, previously reported to remain elevated for at least some exercise formats. This highly preserved pattern indicates the importance of the adaptive response to physical stress across multiple health conditions. [ABSTRACT FROM AUTHOR]

Background Abnormal systemic concentrations of proinflammatory cytokines/chemokines have been implicated in the development of long-term cardiovascular complications in type 1 diabetes (T1DM) and obesity. Whether leukocyte white blood cell (WBC) gene expression of these proinflammatory mediators contributes to their increased systemic levels, however, remains unclear, especially in the pediatric patient populations. This study examines mRNA changes of 9 cytokines and chemokines in WBCs following ex vivo immunostimulation from 9 T1DM (13.4 ± 0.5 year, 4F/5 M), 23 overweight (OW, 12.3 ± 0.5 year, 10F/13M, BMI% 97.1 ± 0.5 and > 90.0), and 21 healthy (CL, 13.8 ± 0.7 year, 9F/12 M, BMI% 59.6 ± 4.6 and < 85.0) children. Methods All subjects had been maintained in euglycemic conditions for at least 90 min before blood draws. Whole blood was then sampled and incubated with anti-T-cell receptor (TCR) antibody or heat-aggregated IgG (HAG) to stimulate T-cell and Fc receptors (FcR), respectively. After lysis of leukocytes, mRNA levels of six tumor necrosis factor superfamily cytokines (TNFSF2, 5, 6, 7, 9, 14) and three chemokines (CCL8, 20, and CXCL10) were measured using RT-PCR. Results Following TCR stimulation, T1DM displayed significantly greater mRNA responses than CL for TNFSF5, 7, 9, and CCL8, and CXCL10; TNFSF9, CCL8, and CXCL10 were also significantly higher in T1DM than OW; no difference was observed between OW and CL. FcR stimulation induced similar responses across groups. Conclusions Leukocytes of T1DM children displayed exaggerated gene expression in response to ex vivo TCR induction of five key proinflammatory cytokines/chemokines. This elevated leukocyte gene expression may be one of the pathophysiological contributors to the development of vascular complications in T1DM. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a case study of 16-year-old adolescent boy with recurrent dizziness and syncope. Sinus bradycardia was revealed by an electrocardiogram (ECG), a heart rate of 47 beats/min, and a QT interval of 663 ms. Other symptoms and diagnosed problems were long QT syndrome (LQTS), and recurrent nonsustained polymorphic ventricular tachycardia.

The health effects of exercise depend on a complex equilibrium of often opposing mechanisms that may become altered in pathological states. In type 1 diabetes (T1DM), leukocyte activity dysregulation strongly correlates with diabetic vascular complications; it may therefore be important to identify alterations in exercise-induced leukocyte responses (total/fractional WBC counts, changes in leukocyte gene expression of immuno-modulatory factors). Little is known, however, about these responses, particularly in children. This study therefore investigated exercise-induced changes in leukocyte counts and mRNA expression of IL-6, IL- 10, VEGF, COX2, CD11a and HSP70 in control (n = 24, 14.1 ± 0.7 yrs, 8M/16F) and T1DM (n = 13, 13.3 ± 0.5 yrs, 8M/5F) children. Exercise consisted of 10 bouts of 2-min cycling at 80% VO2max separated by 1-min rest. For at least 90 min prior to and during exercise, euglycemia (80-110 mg/dL) was maintained for T1DM. Blood was drawn at baseline, end-exercise and 30-min post. mRNA expression was calculated as ratios of individual mRNAs and mRNA of the housekeeping protein β-actin to normalize for leukocytosis. The exercise-induced increase in WBC concentrations, observed in controls, was well preserved in T1DM. By 30-min post exercise, neutrophil and monocyte counts returned to baseline in both groups, while lymphocytes dipped below baseline. At end-exercise, WBC VEGF mRNA expression was significantly greater in T1DM than controls (p=0.041), while no difference was measured for other tested genes. Our data show that while the overall leukocytic response to exercise is well preserved in T1DM children, a significant alteration was present in the WBC mRNA expression of at least one major immune-modulator, VEGF, implicated in the pathological thickening of extracellular matrix causing reduced arterial perfusion. Our observations underscore the need for a deeper understanding of all aspects of exercise adaptation in populations at increased risk of long-term cardiovascular complications, including T1DM children. [ABSTRACT FROM AUTHOR]

Understanding the kinetic profiles of immunomodulatory factors during physical activity may help optimize the health benefits of exercise. This may be especially relevant for children with Type 1 Diabetes (T1DM), in which an imbalance of pro-/anti-inflammatory mediators that accelerates diabetic vascular complications may occur during/following exercise due to prior glycemic fluctuations. To date, exercise-induced alterations in immunomoduatory mediators in T1DM children remain largely unknown. This study examines 21 healthy (CNTRL, 13.9 ± 0.8 yrs, 8M/13F) and 21 diabetic (T1DM, 13.4 ± 0.3 yrs, 13M/8F) children. Blood glucose of T1DM was kept in the 80-110 mg/dL range for at least 90 min prior to and during exercise (ten 2-min cycling bouts at 80% VO2max, separated by 1-min intervals). Blood samples were drawn every second exercise bout, and at 15 and 30 min post exercise. In CNTRL, most tested mediators decreased during the first 15 min of exercise; some then increased slightly, remaining at or below baseline by end-exercise (the pro-inflammatory TNF-α, IL-12p70, GM-CSF, Eotaxin, MCP-1, and the anti-inflammatory IL-4); others clearly increased above baseline (IL-1α, IL-6, IL-8 IL-17, and MIP-1α, all pro-inflammatory/chemo-attractants). Conversely, in T1DM, the initial decrease was not observed, and most variables increased above baseline more markedly and more rapidly, resulting in significant differences in kinetic profiles vs CNTRL for TNF-α GM-CSF, Eotaxin, MCP-1, MIP-1α (10<0.05 - 0.001, AUC), and a significantly earlier time to peak values for IL-6, IL-17, and MIP-1α (p<0.05). The profile of the pro-inflammatory chemokine, IP-10, was similar between the 2 groups. During intense, intermittent exercise, the initial anti-inflammatory adaptation observed in age-matched healthy controls was absent in T1DM children. Further, the exercise-associated pro-inflammatory surge was greater in T1DM as compared to CNTRL. Our data suggest that optimization of exercise conditions may be crucial to maximize the health benefits of exercise in children with diabetes. [ABSTRACT FROM AUTHOR]

Altered leukocyte (WBC) activity, such as hypersecretion of pro-inflammatory cytokine/chemokines in type 1 diabetes (T1DM) has been implicated, in addition to early-stage accelerated damage to residual β cells, in the later onset and progression of vascular complications. Relatively little, however, is known about the regulation of WBC genes expressing pro-inflammatory molecules in response to immune stimuli in T1DM, particularly in children. Our study examines humoral and cell-mediated stimulation WBC cytokine/chemokine mRNA expression in T1DM and non-diabetic (nDM) children using a novel ex-vivo technique. Peripheral blood was drawn after at least 2 h of stable euglycemia in 14 T1DMs (13.2 ± 0.4 yrs, 8M/4F, +2 repeat subjects) and 26 nDMs (14.0 ± 0.6 yrs, 13M/13F). Blood was then incubated for 4 h with heat aggregated IgG (HAG) or anti-TCR antibody at body temperature to stimulate humoral and cell-mediated immune responses, respectively, with appropriate PBS and control IgG as comparisons, mRNA expression was then quantified, following WBC lysis, using a novel RT-PCR methodology developed by our group. Following TCR stimulation, most TNF super-family cytokines (TNFSFs) and CCL/CXCL chemokines displayed significantly increased WBC mRNA expression in T1DMs vs nDMs. Conversely, following HAG stimulation, no difference between groups was observed in for TNFSFs, various interleukins, or chemokines. Our data suggests that in T1DM children, WBC display an exaggerated proinflammatory response to immunologic stimuli that is limited to cell-mediated processes, while inflammatory responses to humoral stimulation appear intact. WBC cytokine expression may therefore contribute, at least in part, to the previously reported increased circulatory levels of pro-inflammatory cytokines in T1DM. While further investigations are needed to test the impact of this cell-mediated hyperactivity on the onset/progression of diabetic vascular complications, our findings may help identify new targets for specific, preventive anti-inflammatory strategies. [ABSTRACT FROM AUTHOR]