The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for oxidative stress, low-grade inflammation and nitric oxide production

Aims To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM). Methods Twenty-five sedentary, obese (BMI > 30 kg/m(2)) males (52.8 +/- 7.2 years); 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max; 30-40 % VO2max) or moderate (T-vent; 55-65 % VO2max) intensity. Before and after training, blood and muscle samples (v. lateralis) were collected. Results Baseline erythrocyte glutathione was lower (21.8 +/- 2.8 vs. 32.7 +/- 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 +/- 52.1 vs. 75.5 +/- 41.6 nmol/ml). Plasma catalase increased in T2DM after T-vent training (from 0.98 +/- 0.22 to 1.96 +/- 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 +/- 2.78 vs. 12.34 +/- 3.56 mu mol/l). Training at T-vent increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers. Conclusion Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T-vent. Non-diabetics responded to T-vent training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention)

The effects of aerobic exercise on oxidative stress and cardiovascular risk factors in aging and type II diabetes mellitus

The oxidation of low-density lipoproteins (LDL) is considered a key step in the development and progression of atherosclerosis. Single bouts of aerobic exercise cause transient increases in free radical production that may enhance the susceptibility of LDL to oxidation and create a more atherogenic LDL particle. In contrast, chronic exercise has often been considered an effective tool in improving metabolic profile through changes in aerobic capacity, lipid profile, fuel utilization and oxidative stress in both healthy and disease populations. Despite this, less is known about how it may benefit the prevention of LDL oxidation and the mechanisms by which this may occur, particularly in aged and patients with type II diabetes who have oxidative stress. The primary aim of the work contained in this thesis, is to examine the effects of aerobic exercise on the susceptibility of LDL to oxidation in both young, aged and type II diabetic subjects. The findings of study 1 demonstrate that an acute bout of moderate intensity exercise can increase the susceptibility of LDL III in both young and aged subjects regardless of any change in LDL lipid composition. Study 2 demonstrates that chronic aerobic exercise of moderate intensity is effective at improving the resistance of the LDL I sub fraction against oxidation, as shown by an increase in T1I2max, despite no change in LDL lipid composition. This intervention was also beneficial in altering maximal aerobic capacity in both young and aged subjects. Study 3 demonstrates that chronic low and moderate intensity aerobic exercise has no effect on LDL oxidative susceptibility. However, chronic moderate intensity exercise increased catalase activity and decreased protein oxidation. The collective findings of this work provide evidence that acute exercise may increase LDL oxidation while chronic exercise may prevent the oxidation of LDL particularly in aged subjects. Further research with greater subject numbers is required to determine the precise mechanism by which exercise influences the susceptibility of LDL oxidation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

Background: Cinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal. Methods: A single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined. Results: Cinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal. Conclusions: 3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies. Trial registration: Trial registration number: at http://www.clinicaltrial.gov: NCT0135028

Analytical validation of a prognostic prostate cancer gene expression assay using formalin fixed paraffin embedded tissue

Abstract Background There is a clear need for assays that can predict the risk of metastatic prostate cancer following curative procedures. Importantly these assays must be analytically robust in order to provide quality data for important clinical decisions. DNA microarray based gene expression assays measure several analytes simultaneously and can present specific challenges to analytical validation. This study describes the analytical validation of one such assay designed to predict metastatic recurrence in prostate cancer using primary formalin fixed paraffin embedded tumour material. Methods Accuracy was evaluated with a method comparison study between the assay development platform (Prostate Disease Specific Array) and an alternative platform (Xcel™ microarray) using 50 formalin-fixed, paraffin-embedded prostate cancer patient samples. An additional 70 samples were used to establish the assay reportable range. Determination of assay precision and sensitivity was performed on multiple technical replicates of three prostate cancer samples across multiple variables (operators, days, runs, reagent lots, and equipment) and RNA/cDNA inputs respectively using the appropriate linear mixed model. Results The overall agreement between the development and alternative platform was 94.7% (95% confidence interval, 86.9–98.5%). The reportable range was determined to be 0.150 to 1.107 for core needle biopsy samples and − 0.214 to 0.844 for radical prostatectomy samples. From the precision study, the standard deviations for assay repeatability and reproducibility were 0.032 and 0.040 respectively. The sensitivity study demonstrated that a total RNA input and cDNA input of 50 ng and 3.5 μg respectively was conservative. Conclusion The Metastatic Assay was found to be highly reproducible and precise. In conclusion the studies demonstrated an acceptable analytical performance for the assay and support its potential use in the clinic