Cardiac function and arteriovenous oxygen difference during exercise in obese adults

The purpose of this study was to assess cardiac function and arteriovenous oxygen difference (a-vO₂ difference) at rest and during exercise in young, normal-weight (n = 20), and obese (n = 12) men and women who were matched for age and fitness level. Participants were assessed for body composition, peak oxygen consumption (VO_2peak), and cardiac variables (thoracic bioimpedance)—cardiac index (CI), cardiac output (Q), stroke volume (SV), heart rate (HR), and ejection fraction (EF)—at rest and during cycling exercise at 65% of VO_2peak. Differences between groups were assessed with multivariate ANOVA and mixed-model ANOVA with repeated measures controlling for sex. Absolute VO_2peak and VO_2peak relative to fat-free mass (FFM) were similar between normal-weight and obese groups (Mean ± SEE 2.7 ± 0.2 vs. 3.3 ± 0.3 l min⁻¹, p = 0.084 and 52.4 ± 1.5 vs. 50.9 ± 2.3 ml kg FFM⁻¹ min⁻¹, p = 0.583, respectively). In the obese group, resting Q and SV were higher (6.7 ± 0.4 vs. 4.9 ± 0.1 l min⁻¹, p < 0.001 and 86.8 ± 4.3 vs. 65.8 ± 1.9 ml min⁻¹, p < 0.001, respectively) and EF lower (56.4 ± 2.2 vs. 65.5 ± 2.2%, p = 0.003, respectively) when compared with the normal-weight group. During submaximal exercise, the obese group demonstrated higher mean CI (8.8 ± 0.3 vs. 7.7 ± 0.2 l min⁻¹ m⁻², p = 0.007, respectively), Q (19.2 ± 0.9 vs. 13.1 ± 0.3 l min⁻¹, p < 0.001, respectively), and SV (123.0 ± 5.6 vs. 88.9 ± 4.1 ml min⁻¹, p < 0.001, respectively) and a lower a-vO₂ difference (10.4 ± 1.0 vs. 14.0 ± 0.7 ml l00 ml⁻¹, p = 0.002, respectively) compared with controls. Our study suggests that the ability to extract oxygen during exercise may be impaired in obese individuals.     

Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DL_CO) and the components of DL_CO (pulmonary capillary blood volume V _c, and alveolar–capillary membrane conductance D _M) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m², peak normoxic VO₂ = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO₂ of 12.5% for 90 min. DLCO, V _c, and D _M were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O₂ saturation and VO_2peak did not differ between the two conditions. DL_CO was not different between groups at any time point. V _C was higher with exercise in the placebo group, and the difference in D _M between sildenafil and placebo was significant only when corrected for changes in V _c (D _M/V _c = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in D _M when corrected for changes in V _c during short-term hypoxic exposure with exercise.     

Impact of the exercise mode on heart rate recovery after maximal exercise

Heart rate recovery 1 min after exercise termination (HRR-1) is a prognostic predictor. However, the influence of the exercise mode on HRR-1 is incompletely characterised. Twenty-nine young and healthy subjects and 16 elderly patients with chronic heart failure underwent cardiopulmonary exercise testing using cycle ergometer and treadmill ramp protocols in random order. HRR-1 and heart rate recovery 2 and 3 min after exercise (HRR-2, HRR-3) during active recovery and peak oxygen consumption (peak VO₂) were measured. In both healthy subjects (32 ± 14 vs. 27 ± 10 bpm) and HF patients (19 ± 8 vs. 14 ± 9 bpm), HRR-1 was faster after cycle exercise (p = 0.029; p for between group difference 0.94). In contrast, HRR-2 and HRR-3 were similar after both tests in both groups. Peak VO₂ was lower during cycle as compared to treadmill exercise in both groups. In conclusion, in both healthy subjects and HF patients, HRR-1 depends on the mode of exercise as peak VO₂ does.     

Hypoxia and cardiac arrhythmias in breath-hold divers during voluntary immersed breath-holds

The incidence and nature of cardiac arrhythmias during static apnea were studied by monitoring the electrocardiogram (ECG) and oxygen saturation (SaO₂) of 16 recreational breath-hold divers. All subjects completed a maximal apnea with a mean (±SD) breath-hold duration of 281 (±73) s without clinical complications. Both heart rate (HR) and SaO₂ decreased significantly with breath-hold duration. The decline in SaO₂ was inversely related to the decline in HR (r = −0.55, P < 0.05). Cardiac arrhythmias (supraventricular and ventricular premature complexes, right bundle branch block) occurred in 12/16 (77%) subjects and were related to breath-hold duration. Subjects with atrial premature complexes (n = 9) had a reduced BMI (P = 0.016) and a higher decline of the terminal SaO₂ (P = 0.01). In conclusion, ectopic arrhythmias were common during maximal static apneas for training purposes. The results indicate that the occurrence of ectopic beats is associated with individual factors such as the tolerable SaO₂ decrease.     

Cardiac vagal withdrawal and reactivation during repeated rest–exercise transitions

It is not known whether subjects that have higher cardiac vagal reactivation (CVR) during repeated exercise transitions also have higher cardiac vagal withdrawal (CVW) at the onset of exercise, which would lead to better heart rate (HR) regulation during exercise transitions. Therefore, our aims were to investigate: (a) the influence of CVR on CVW during repeated rest–exercise transitions; and (b) the influence of the sympathetic activity on CVR and CVW. Fifty-eight healthy men (22 ± 4 years) performed 20 rest–exercise transitions interspaced by 30 s. In addition, nine healthy men (24 ± 3 years) ingested either 25 mg of atenolol or placebo, on a crossover, double-blind, randomized design, then performed 20 rest–exercise transitions interspaced by 30 s. Cardiac vagal reactivation was assessed by a HR variability index (RMSSD) and CVW by the HR increase at the onset of a valid and reliable cycling protocol. The CVR and CVW responses were associated (partial r ranged from 0.60 to 0.66; p < 0.05). Participants with higher CVR over transitions maintained their CVW over repeated transitions [first transition (mean ± SEM) = 1.59 ± 0.04 vs. 20th = 1.50 ± 0.03 (a.u.), p = 0.24], while participants with lower CVR had a CVW decrease over repeated transitions [first transition (mean ± SEM) = 1.38 ± 0.04 vs. 20th = 1.19 ± 0.03 (a.u.), p < 0.01). In addition, the CVR and CVW over the rest–exercise transitions were similar during atenolol and placebo (ANCOVA interaction p = 0.12 and p = 0.48, respectively). In conclusion, the CVR among repeated rest–exercise transitions influenced the CVW at the onset of exercise, which was not affected by a partial β₁ cardioselective adrenoceptor blockade.     

Sildenafil does not improve steady state cardiovascular hemodynamics, peak power, or 15-km time trial cycling performance at simulated moderate or high altitudes in men and women

Sildenafil improves oxygen delivery and maximal exercise capacity at very high altitudes (≥4,350 m), but it is unknown whether sildenafil improves these variables and longer-duration exercise performance at moderate and high altitudes where competitions are more common. The purpose of this study was to determine the effects of sildenafil on cardiovascular hemodynamics, arterial oxygen saturation (SaO₂), peak exercise capacity (W _peak), and 15-km time trial performance in endurance-trained subjects at simulated moderate (MA; ~2,100 m, 16.2% F_IO₂) and high (HA; ~3,900 m, 12.8% F_IO₂) altitudes. Eleven men and ten women completed two HA W _peak trials after ingesting placebo or 50 mg sildenafil. Subjects then completed four exercise trials (30 min at 55% of altitude-specific W _peak + 15-km time trial) at MA and HA after ingesting placebo or 50 mg sildenafil. All trials were performed in randomized, counterbalanced, and double-blind fashion. Sildenafil had little influence on cardiovascular hemodynamics at MA or HA, but did result in higher SaO₂ values (+3%, p < 0.05) compared to placebo during steady state and time trial exercise at HA. W _peak at HA was 19% lower than SL (p < 0.001) and was not significantly affected by sildenafil. Similarly, the significantly slower time trial performance at MA (28.1 ± 0.5 min, p = 0.016) and HA (30.3 ± 0.6 min, p < 0.001) compared to SL (27.5 ± 0.6 min) was unaffected by sildenafil. We conclude that sildenafil is unlikely to exert beneficial effects at altitudes <4,000 m for a majority of the population.     

Diversity and association of HLA/KIR receptors with type 2 diabetes in South India

The present study was undertaken to delineate the association(s) of KIR–HLA combination in South Indian Type 2 diabetes mellitus (T2DM) patients. The T2DM patients (n = 343) and healthy controls (n = 309) were genotyped for KIR/HLA ligands by PCR‐SSP method. The increased frequency of activatory KIR (aKIR) 2DS2 (OR = 1.91; p < 2.91 × 10^?4) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR = 0.38; p < 1.55 × 10^?5) and aKIRs 2DS1 (OR = 0.60; p < 0.001) and 3DS1 (OR = 0.52; p < 5.83 × 10^?5) were decreased in patients suggesting protective associations. The C1/C2 combinatorial analysis has revealed an increased frequency of C1⁺/C2^? in T2DM patients (OR = 1.62; p < 0.014). The KIR “AB” genotype (OR = 2.41; p < 3.87 × 10^?5) was observed to be higher in patients. However, the “BB” genotype (OR = 0.32; p < 4.71 × 10^?7) was increased in controls. The KIR motifs, “Tel‐B/B” (OR = 1.84; p < 0.007), were observed higher among patients. However, the frequency of “Tel‐A/B” motif genotype was decreased in patients (OR = 0.56; p < 3.13 × 10^?4). The iKIR/HLA combinations such as 2DL2/3 +C1 and 3DL2+A3/A11 were increased in patients (OR = 3.90; p < 7.5 × 10^?5) suggesting susceptible associations. On the contrary, the aKIR+HLA combinations such as 2DS2+C1, 2DS1+C2 and 3DS1+Bw4 were less frequent in patients (OR = 0.32; p < 4.2 × 10^?4) suggesting protective associations. Thus, the present study clearly establishes the positive and negative associations of different KIR–HLA receptor combinations with T2DM in South India.     

In-vivo assessment of T cell kinetics in individuals at risk for type 1 diabetes

We previously assessed the kinetics of T cell turnover in vivo by labeling cells with ²H-H₂O over 42 days in individuals with type 1 diabetes (T1D) and demonstrated an increased turnover of CD4 memory T cells. We have now tested T cell turnover in individuals at risk for T1D using a 3–4-day labeling protocol with ²H-glucose. We studied 30 relatives with T1D with and without autoantibodies, and 10 healthy controls. Peripheral blood mononuclear cells (PBMC) were flow-sorted into T cell subsets of interest; ²H-DNA enrichment was measured by mass spectrometry and in-vivo turnover was calculated as maximum fractional enrichment of deuterated adenosine (F_max). Among CD4⁺ cells, F_max was highest in regulatory T cells (T_reg), followed by effector and central memory T cells and lowest in naive cells. Similarly, CD8⁺ central and effector memory T cells had a higher turnover than CD8⁺ terminally differentiated effector memory T cells (TEMRA) and CD8⁺-naive T cells. Relatives as a group showed significantly increased T_reg turnover by F_max compared to controls (1·733 ± 0·6784% versus 1·062 ± 0·3787%, P = 0·004), suggesting pre-existing immune dysfunction within families with T1D. However, there was no significant difference in F_max between groups according to autoantibody or glucose tolerance status. Repeat testing in 20 subjects 1 year later demonstrated relatively higher within-subject compared to between-subject variability for the measurement of F_max in various T cell subsets. The short labeling protocol with ²H-glucose should be applied in the context of a clinical trial in which the therapy is expected to have large effects on T cell turnover.     

Lung-to-lung circulation times during exercise in heart failure

Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 ± 14 year, resting ejection fraction = 23 ± 8%) and control subjects (51 ± 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C₂H₂ washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 ± 8.2 s, Q = 4.3 ± 1.1 l min⁻¹; control: LLCT = 55.3 ± 10.9 s, Q = 4.5 ± 0.5 l min⁻¹) to peak exercise (HF:LLCT = 20.6 ± 3.9* s, Q = 8.8 ± 2.5* l min⁻¹; control:LLCT = 14.9 ± 2.4 s, Q = 16.5 ± 1.2 l min⁻¹; *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.     

Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension

Impaired O₂ delivery relative to O₂ demands at the onset of exercise might influence the response profile of muscle fractional O₂ extraction (≅Δ[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an “overshoot” (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O₂ uptake ( [(V)\dot]\textO₂ ), \left( {\dot{V}{\text{O}}_{2} } \right), Δ[deoxy-Hb/Mb] in the vastus lateralis, and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (connective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} and HR dynamics than controls (τ [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2}  = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t ^1/2-HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p < 0.01). No study participant had a significant reduction in oxyhemoglobin saturation. In OS(−) subjects (6 patients and 7 controls), the kinetics of Δ[deoxy-Hb/Mb] relative to [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} were faster in patients (p = 0.05). Larger area under the OS and slower kinetics (MRT) of the “downward” component indicated greater O₂ delivery-to-utilization mismatch in OS(+) patients versus OS(+) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p < 0.05). Resting pulmonary vascular resistance was higher in OS(+) than OS(−) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p < 0.05). We conclude that microvascular O₂ delivery-to-utilization inequalities slowed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH.     

Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations

Betacellulin, a member of the epidermal growth factor family, is expressed in fetal and adult pancreas. In vitro and in vivo studies suggest a role for betacellulin in islet neogenesis and regeneration. Therefore, a mutation in the betacellulin gene might lead to fewer beta cells. With reduced beta cell reserve, beta cells may not be able to compensate for an autoimmune attack, and in turn, susceptibility to type 1 diabetes mellitus (T1DM) would increase. Previous mutational analysis identified seven polymorphisms in the betacellulin gene [5′ UT (−233G>C, −226A>G), exon 1 (TGC19GGC, Cys7Gly), exon 2 (CTC130TTC, Leu44Phe), exon 4 (TTG370ATG, Leu124Met), intron 2 (-31T>C), and intron 4 (-4C>T)]. An association study of these variants with T1DM was first carried out in 100 Caucasian subjects with T1DM and 282 Caucasian subjects without diabetes recruited at the University of Maryland. The frequency of the intron 4 T-4 allele was significantly higher among nondiabetic controls than that among diabetic cases (0.29 vs 0.21, p=0.04). Allele frequencies for the other polymorphisms did not differ significantly between cases and controls. The intron 4 T-4 association was then replicated by transmission disequilibrium testing in a separate population of Caucasian parent/offspring with T1DM trios (n=168 trios, 113 informative) recruited at the Medical College of Wisconsin (p=0.024). An interaction of the intron 4 T-4 allele and human leukocyte antigen (HLA) was also detected with undertransmission of the T allele in those T1DM subjects with susceptible HLA types as compared to those T1DM subjects without susceptible HLA types (p=0.018). RNA studies of the intron T-4 variant showed similar RNA levels for intron 4 T-4 and intron 4 C-4 alleles. Additionally, there was no evidence for an effect of this variant on exon–intron splicing. We conclude that the intron 4 T-4 allele in the betacellulin gene is associated with lower risk of T1DM and may interact with HLA. Further studies will be necessary to establish the significance of this association.     

Evidence of increased electro-mechanical delay in the left and right ventricle after prolonged exercise

We assessed the time delay from the onset of QRS (Q) to peak systolic (S′) and diastolic (E′) tissue velocities in the left (LV) and right ventricle (RV) before and after prolonged exercise. Nineteen well-trained runners (mean ± SD age, 41 ± 9 years) had tissue-Doppler echocardiography performed before and after an 89 km ultra-marathon race. Longitudinal tissue motion was analysed in LV basal and mid-wall segments and RV free wall. Electromechanical coupling was assessed by the delay between Q and S′ as well as E′ tissue velocities. Average data for all segments were adjusted for the R–R interval. Comparisons were made by paired t-tests. An increase in electro-mechanical delay (EMD) was reported post-exercise in systole (Q–S′ LV: 131 ± 20 vs. 175 ± 27 ms; RV: 171 ± 34 vs. 258 ± 35 ms; P < 0.05) and diastole (Q–E′ LV: 486 ± 51 vs. 647 ± 44 ms; RV: 500 ± 80 vs. 690 ± 75 ms; P < 0.05). Further, post-race peak tissue velocities in basal LV and RV wall segments were reduced (P < 0.05). Recovery from prolonged running was associated with an increased “EMD”, and reduced peak tissue velocities, in both ventricles.     

Pulmonary oxygen uptake and muscle deoxygenation kinetics during recovery in trained and untrained male adolescents

Previous studies have demonstrated faster pulmonary oxygen uptake ( [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} ) kinetics in the trained state during the transition to and from moderate-intensity exercise in adults. Whilst a similar effect of training status has previously been observed during the on-transition in adolescents, whether this is also observed during recovery from exercise is presently unknown. The aim of the present study was therefore to examine [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics in trained and untrained male adolescents during recovery from moderate-intensity exercise. 15 trained (15 ± 0.8 years, [(V)\dot]\textO_2max \dot{V}{\text{O}}_{2\max} 54.9 ± 6.4 mL kg⁻¹ min⁻¹) and 8 untrained (15 ± 0.5 years, [(V)\dot]\textO_2max \dot{V}{\text{O}}_{2\max } 44.0 ± 4.6 mL kg⁻¹ min⁻¹) male adolescents performed two 6-min exercise off-transitions to 10 W from a preceding “baseline” of exercise at a workload equivalent to 80% lactate threshold; [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} (breath-by-breath) and muscle deoxyhaemoglobin (near-infrared spectroscopy) were measured continuously. The time constant of the fundamental phase of [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} off-kinetics was not different between trained and untrained (trained 27.8 ± 5.9 s vs. untrained 28.9 ± 7.6 s, P = 0.71). However, the time constant (trained 17.0 ± 7.5 s vs. untrained 32 ± 11 s, P < 0.01) and mean response time (trained 24.2 ± 9.2 s vs. untrained 34 ± 13 s, P = 0.05) of muscle deoxyhaemoglobin off-kinetics was faster in the trained subjects compared to the untrained subjects. [(V)\dot]\textO₂ \dot{V}{\text{O}}_{2} kinetics was unaffected by training status; the faster muscle deoxyhaemoglobin kinetics in the trained subjects thus indicates slower blood flow kinetics during recovery from exercise compared to the untrained subjects.     

Lactate kinetics in human tissues at rest and during exercise

Aim: We sought to determine whether pulmonary diffusing capacity for nitric oxide (DLNO), carbon monoxide (DLCO) and pulmonary capillary blood volume (Vc) at rest predict peak aerobic capacity (O_2peak), and if so, to discern which measure predicts better. Methods: Thirty-five individuals with extreme obesity (body mass index or BMI = 50 ± 8 kg m⁻²) and 26 fit, non-obese subjects (BMI = 23 ± 2 kg m⁻²) participated. DLNO and DLCO at rest were first measured. Then, subjects performed a graded exercise test on a cycle ergometer to determine O_2peak. Multivariate regression was used to assess relations in the data. Results: Findings indicate that (i) pulmonary diffusion at rest predicts O_2peak in the fit and obese when measured with DLNO, but only in the fit when measured with DLCO; (ii) the observed relation between pulmonary diffusion at rest and O_2peak is different in the fit and obese; (iii) DLNO explains O_2peak better than DLCO or Vc. The findings imply the following reference equations for DLNO: O_2peak (mL kg⁻¹ min⁻¹) = 6.81 + 0.27 × DLNO for fit individuals; O_2peak (mL kg⁻¹ min⁻¹) = 6.81 + 0.06 × DLNO, for obese individuals (in both groups, adjusted R² = 0.92; RMSE = 5.58). Conclusion: Pulmonary diffusion at rest predicts O_2peak, although a relation exists for obese subjects only when DLNO is used, and the magnitude of the relation depends on gender when either DLCO or Vc is used. We recommend DLNO as a measure of pulmonary diffusion, both for its ease of collection as well as its tighter relation with O_2peak.     

Ultra short-term heart rate recovery after maximal exercise in continuous versus intermittent endurance athletes

This study tested the hypothesis that athletes participating in intermittent sports would exhibit a faster heart rate recovery (HRR) during the initial phase (<30 s) following maximal exercise than athletes participating in continuous endurance sports. Forty-six male athletes were allocated into continuous (CNT, n = 24) or intermittent groups (INT, n = 22), matched for age and aerobic fitness. Athletes performed maximal exercise on a treadmill using the ramp protocol. Immediately upon exercise cessation, subjects were placed supine with continuous measurement of HR during the first minute of recovery. Data were analyzed in 10-s intervals and compared between the groups. Repeated measures ANOVA showed a group × time interaction effects (p ≤ 0.01) for HRR expressed in both beats min⁻¹ and in percentage of peak post-exercise HR (% HR_peak). The INT group had lower HR than CNT group at 10 s (189 vs. 192 beats min⁻¹, p = 0.04; and 96.3 vs. 97.9% HR_peak, p = 0.009) and 20 s (184 vs. 188 beats min⁻¹, p = 0.049; and 93.6 vs. 95.7% HR_peak, p = 0.021) intervals of recovery. The results suggest that athletes engaged in intermittent sports are likely to have faster HRR during the first 20 s after maximal exercise than their counterparts trained for continuous performance.     

PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients

Type 1 diabetes (T1DM) is a common autoimmune disease with a complex genetic background. This study was aimed to investigate the association of PTPN22 G(-1123)C and C1858T, PDCD1 G7146A and CYP27B1 C(-1260)A polymorphisms with T1DM among Polish subjects. The PTPN22 gene encodes lymphoid tyrosine phosphatase, a potent negative regulator of T cell activation. PDCD1 gene gives rise to an inhibitory cell-surface receptor, expressed on activated lymphocytes. CYP27B1 encodes 1-alpha hydroxylase, responsible for conversion of the vitamin D₃ precursor into its active form, involved in the immune function. Polymorphic variants of these genes have previously been associated with various autoimmune disorders. The four polymorphisms were genotyped by PCR-restriction fragment assays in a case–control study comprising 215 T1DM patients and 236 healthy controls. The PTPN22 T1858 allele appeared significantly increased in T1DM compared to the control group (P = 0.004), yielding an OR of 1.73 (95% CI 1.19–2.51). The difference in distribution of C1858T genotypes also demonstrated statistical significance (P = 0.015). The frequencies of PTPN22 G(-1123)C alleles and genotypes did not differ between T1DM cases and controls, although the haplotype comprising both mutant PTPN22 alleles, C(-1123) and T1858, was significantly more frequent in affected individuals (P = 0.003). G(-1123)C and C1858T were in linkage disequilibrium (D′ = 0.98; r² = 0.61 in T1DM and D′ = 0.97; r² = 0.41 in controls). No significant differences in the allele and genotype frequencies of PDCD1 and CYP27B1 polymorphisms were found between patients and controls. This study confirms the association of PTPN22 C1858T polymorphism with T1DM, whereas the effects of PTPN22 G(-1123)C, PDCD1 G7146A and CYP27B1 C(-1260)A seem unlikely, at least in the Polish population.     

Men and women exhibit a similar time to task failure for a sustained,submaximal elbow extensor contraction

Sex differences in muscle fatigue-resistance have been observed in a variety of muscles and under several conditions. This study compared the time to task failure (TTF) of a sustained isometric elbow extensor (intensity 15% of maximal strength) contraction in young men (n = 12) and women (n = 11), and examined if their neurophysiologic adjustments to fatigue differed. Motor-evoked potential amplitude (MEP), silent period duration, interference electromyogram (EMG) amplitude, maximal muscle action potential (M _max), heart rate, and mean arterial pressure were measured at baseline, during the task, and during a 2-min ischemia period. Men and women did not differ in TTF (478.2 ± 31.9 vs. 500.4 ± 41.3 s; P = 0.67). We also performed an exploratory post hoc cluster analysis, and classified subjects as low (n = 15) or high endurance (n = 8) based on TTF (415.3 ± 16.0 vs. 626.7 ± 25.8 s, respectively). The high-endurance group exhibited a lower MEP and EMG at baseline (MEP 16.3 ± 4.1 vs. 37.2 ± 3.0% M _max, P < 0.01; EMG 0.98 ± 0.18 vs. 1.85 ± 0.26% M _max, P = 0.03). These findings suggest no sex differences in elbow extensor fatigability, in contrast to observations from other muscle groups. The cluster analyses results indicated that high- and low-endurance groups displayed neurophysiologic differences at baseline (before performing the fatigue task), but that they did not differ in fatigue-induced changes in their neurophysiologic adjustments to the task.     

A comparison of normal versus low dietary carbohydrate intake on substrate oxidation during and after moderate intensity exercise in women

We compared the effects of consuming a 2-day low-carbohydrate (CHO) diet (low-CHO; 20% CHO, 40% protein, 40% fat) versus an isocaloric 2-day moderate-CHO diet (mod-CHO; 55% CHO, 15% protein, 30% fat) on substrate oxidation during and after exercise in ten active, young women. Subjects were 24.9 ± 6.2% body fat with a VO_2max of 68.8 ± 13.8 ml/kg FFM/min. For 2 days prior to exercise, subjects consumed either the mod-CHO or the low-CHO diet and then completed treadmill exercise at 55% of VO_2max until 350 kcal of energy was expended. During exercise and for 2 h post-exercise, expired gases were analyzed to determine oxidation rates for CHO (CHO-OX) and fat (FAT-OX). Significant differences (p < 0.05) were found between diets for CHO-OX and FAT-OX (mg/kg FFM/min) during exercise, 1 h post-ex, and 2 h post-ex. During exercise, FAT-OX was higher (low-CHO 8.7 ± 2.2 vs. mod-CHO 6.2 ± 2.2) and CHO-OX was lower (low-CHO 25.1 ± 5.6 vs. mod-CHO 31.1 ± 6.2) following the low-CHO diet. A similar trend was observed during 1 h post-ex for FAT-OX (low-CHO 2.2 ± 0.5 vs. mod-CHO 1.6 ± 0.5) and CHO-OX (low-CHO 2.5 ± 1.2 vs. mod-CHO 4.1 ± 1.9), as well as 2 h post-ex for FAT-OX (low-CHO vs. 1.9 ± 0.5 mod-CHO 1.7 ± 0.4) and CHO-OX (low-CHO 2.5 ± 0.9 vs. mod-CHO 3.1 ± 1.1). Significant positive correlations were observed between VO_2max and CHO-OX during exercise and post-exercise, as well as significant negative correlations between VO_2max and FAT-OX post-exercise in the low-CHO condition. Waist circumference and FAT-OX exhibited a significant negative correlation during exercise in the low-CHO condition. Dietary macronutrient intake influenced substrate oxidation in active young women during and after moderate intensity exercise.     

Overshoot phenomenon of oxygen uptake during recovery from maximal exercise in patients with previous myocardial infarction

The overshoot in oxygen uptake ([(V)\dot] \dot{\rm{V}} O₂ overshoot) during recovery from maximal exercise is thought to reflect an overshoot in cardiac output. We investigated whether this phenomenon is related to cardiopulmonary function during exercise in cardiac patients. A total of 201 consecutive patients with previous myocardial infarction underwent cardiopulmonary exercise testing (CPX). An apparent [(V)\dot] \dot{\rm{V}} O₂ overshoot during the recovery from CPX (6.5 ± 8.1% increase relative to the peak [(V)\dot] \dot{\rm{V}} O₂) was observed in ten patients. A comparison of patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot to those without the [(V)\dot] \dot{\rm{V}} O₂ overshoot revealed that the former had a significantly lower left ventricular ejection fraction (40.1 ± 19.1 vs. 55. 2 ± 14.9%, respectively, p = 0.002) and larger left ventricular diastolic and systolic dimensions. Patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot also had a significantly lower peak [(V)\dot] \dot{\rm{V}} O₂ (13.1 ± 6.1 vs. 18.1 ± 4.5 ml/min/kg, p < 0.001), lower Δ[(V)\dot] \dot{\rm{V}} O₂/ΔWR (work rate) (6.6 ± 3.8 vs. 9.5 ± 1.7 mL/min/W, p < 0.0001), and a higher [(V)\dot] \dot{\rm{V}} E (minute ventilation)/[(V)\dot] \dot{\rm{V}} CO₂ (carbon dioxide output) slope (45.0 ± 18.6 vs. 32.6 ± 6.6, p < 0.0001) than those without the overshoot. A [(V)\dot] \dot{\rm{V}} O₂ overshoot during recovery from maximal exercise was found in 5% of patients with previous myocardial infarction. This condition, which suggests a transient mismatch between cardiac contractility and afterload reduction, was found to be related to impaired cardiopulmonary function during exercise.     

Restoration of blood pH between repeated bouts of high-intensity exercise: effects of various active-recovery protocols

To determine which active-recovery protocol would reduce faster the high blood H⁺ and lactate concentrations produced by repeated bouts of high-intensity exercise (HIE). On three occasions, 11 moderately trained males performed 4 bouts (1.5 min) at 163% of their respiratory compensation threshold (RCT) interspersed with active-recovery: (1) 4.5 min pedalling at 24% RCT (S_HORT); (2) 6 min at 18% RCT (M_EDIUM); (3) 9 min at 12% RCT (L_ONG). The total work completed during recovery was the same in all three trials. Respiratory gases and arterialized-blood samples were obtained during exercise. At the end of exercise, L_ONG in comparison to S_HORT and M_EDIUM increased plasma pH (7.32 ± 0.02 vs. ~7.22 ± 0.03; P < 0.05), while reduced lactate concentration (8.5 ± 0.9 vs. ~10.9 ± 0.8 mM; P < 0.05). Ventilatory equivalent for CO₂ was higher in L_ONG than S_HORT and M_EDIUM (31.4 ± 0.5 vs. ~29.6 ± 0.5; P < 0.05). Low-intensity prolonged recovery between repeated bouts of HIE maximized H⁺ and lactate removal likely by enhancing CO₂ unloading.