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/m2) 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% VO(2max)) or moderate (T(vent); 55-65 % VO(2max)) 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 µmol/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).

Responses to oral glucose challenge differ by physical activity volume and intensity: A pilot study.

BACKGROUND: One-hour postprandial hyperglycemia is associated with increased risk of type 2 diabetes and cardiovascular disease. Physical activity (PA) has short-term beneficial effects on post-meal glucose response. This study compared the oral glucose tolerance test results of 3 groups of people with habitually different levels of PA. METHODS: Thirty-one adults without diabetes (age 25.9 ± 6.6 years; body mass index 23.8 ± 3.8 kg/m2; mean ± SD) were recruited and divided into 3 groups based on self-reported PA volume and intensity: low activity < 30 min/day of moderate-intensity activity (n = 11), moderately active ≥ 30 min/day of moderate-intensity PA (n = 10), and very active ≥ 60 min/day of PA at high intensity (n = 10). Participants completed an oral glucose tolerance test (50 g glucose) with capillary blood samples obtained at baseline, 15 min, 30 min, 45 min, 60 min, 90 min, and 120 min post-ingestion. RESULTS: There were no significant differences between groups for age or body fat percentage or glycated hemoglobin (p > 0.05). The groups were significantly different in terms of baseline glucose level (p = 0.003) and, marginally, for gender (p = 0.053) and BMI (p = 0.050). There was a statistically significant effect of PA on the 1-h postprandial glucose results (p = 0.029), with differences between very active and low activity groups (p = 0.008) but not between the moderately active and low activity groups (p = 0.360), even when baseline glucose level and gender differences were accounted for. For incremental area under the curve there was no significant effect of activity group once gender and body fat percentage had been accounted for (p = 0.401). Those in the low activity group took 15 min longer to reach peak glucose level than those in the very active group (p = 0.012). CONCLUSION: The results suggest that high levels of PA have a beneficial effect on postprandial blood glucose profiles when compared to low and moderate levels of activity.

Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide.

It is now widely accepted that hypertension and endothelial dysfunction are associated with an insulin-resistant state and thus with the development of T2DM (Type 2 diabetes mellitus). Insulin signalling is impaired in target cells and tissues, indicating that common molecular signals are involved. The free radical NO* regulates cell metabolism, insulin signalling and secretion, vascular tone, neurotransmission and immune system function. NO* synthesis is essential for vasodilation, the maintenance of blood pressure and glucose uptake and, thus, if levels of NO* are decreased, insulin resistance and hypertension will result. Decreased blood levels of insulin, increased AngII (angiotensin II), hyperhomocysteinaemia, increased ADMA (asymmetric omega-NG,NG-dimethylarginine) and low plasma L-arginine are all conditions likely to decrease NO* production and which are associated with diabetes and cardiovascular disease. We suggest in the present article that the widely reported beneficial effects of exercise in the improvement of metabolic and cardiovascular health are mediated by enhancing the flux of muscle- and kidney-derived amino acids to pancreatic and vascular endothelial cells aiding the intracellular production of NO*, therefore resulting in normalization of insulin secretion, vascular tone and insulin sensitivity. Exercise may also have an impact on AngII and ADMA signalling and the production of pro- and anti-inflammatory cytokines in muscle, so reducing the progression and development of vascular disease and diabetes. NO* synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects.

Exercise prescription in the treatment of type 2 diabetes mellitus : current practices, existing guidelines and future directions.

Exercise is an effective treatment for type 2 diabetes mellitus, resulting in stabilization of plasma glucose in the acute phase and improvements in body composition, insulin resistance and glycosylated haemoglobin with chronic exercise training. However, the most appropriate exercise prescription for type 2 diabetes has not yet been established, resulting from insufficient evidence to determine the optimum type, intensity, duration or frequency of exercise training. Furthermore, patient engagement in exercise is suboptimal. There are many likely reasons for low engagement in exercise; one possible contributory factor may be a tendency for expert bodies to prioritize the roles of diet and medication over exercise in their treatment guidelines. Published treatment guidelines vary in their approach to exercise training, but most agencies suggest that people with type 2 diabetes engage in 150 min of moderate to vigorous aerobic exercise per week. This prescription is similar to the established guidelines for cardiovascular health in the general population. Future possibilities in this area include investigation of the physiological effects and practical benefits of exercise training of different intensities in type 2 diabetes, and the use of individualized prescription to maximize the health benefits of training.

Differential nitric oxide levels in the blood and skeletal muscle of type 2 diabetic subjects may be consequence of adiposity: a preliminary study.

BACKGROUND AND AIMS: Nitric oxide (NO·) exerts key regulatory functions including vasodilation and glucose uptake. Thus reduced NO· levels are associated with insulin resistance and hypertension. In this preliminary work we aimed to measure the levels of NO· metabolites in serum and skeletal muscle of obese and non-obese subjects, with or without type 2 diabetes mellitus (T2DM). METHODS: Fifteen sedentary male participants [7 obese controls (C) vs 5 obese and 3 non-obese T2DM; age 54±9 years] were selected according to their BMI (>30 kg/m(2) for obese and 23-27 kg/m(2) for non-obese participants) and evaluated for fasted values of blood glucose, HbA1c, lipid profile, serum CRP (C-reactive protein), erythrocyte glutathione (GSH) metabolism, plasma adiponectin, leptin and cytokines (TNF-α and INFγ), serum and skeletal muscle nitric oxide metabolites (nitrite and nitrates; tNOx) and skeletal muscle nNOS and iNOS expression. Body composition was measured by whole body DEXA and muscle microbiopsy was performed in the vastus lateralis. RESULTS: We found that serum tNOx (total nitrite/nitrate; µmol/L) was lower in obese T2DM group (12.7±3.5) when compared with their controls (21.1±2.4), although the non-obese group presented higher concentration of tNOx (33.8±7.2). Skeletal muscle nNOS was higher in obese controls, lower in non-obese T2DM and undetected in obese T2DM. On the other hand, expression of iNOS had an inverse relationship with nNOS, showing higher expression in obese T2DM, decrease in non-obese T2DM and absence in obese control group. tNOx levels (µmol/mg protein) were decreased in the non-obese T2DM group (12.07±0.59) when compared with the obese control (21.68±6.2) and the obese T2DM group (26.3±7.26). CONCLUSION: We conclude that the decreased serum NO∙ production in obese T2DM patients seems to be associated with adipose mass as lower adiposity was associated with normal NO∙ which was reduced in the skeletal muscle of the non-obese T2DM patients. We suggest that the lower adiposity (and higher adiponectin) in non-obese T2DM could be responsible for differential levels of NO∙ production and insulin resistance.