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1.  Muscle-Strengthening and Conditioning Activities and Risk of Type 2 Diabetes: A Prospective Study in Two Cohorts of US Women 
PLoS Medicine  2014;11(1):e1001587.
Anders Grøntved and colleagues examined whether women who perform muscle-strengthening and conditioning activities have an associated reduced risk of type 2 diabetes mellitus.
Please see later in the article for the Editors' Summary
Background
It is well established that aerobic physical activity can lower the risk of type 2 diabetes (T2D), but whether muscle-strengthening activities are beneficial for the prevention of T2D is unclear. This study examined the association of muscle-strengthening activities with the risk of T2D in women.
Methods and Findings
We prospectively followed up 99,316 middle-aged and older women for 8 years from the Nurses' Health Study ([NHS] aged 53–81 years, 2000–2008) and Nurses' Health Study II ([NHSII] aged 36–55 years, 2001–2009), who were free of diabetes, cancer, and cardiovascular diseases at baseline. Participants reported weekly time spent on resistance exercise, lower intensity muscular conditioning exercises (yoga, stretching, toning), and aerobic moderate and vigorous physical activity (MVPA) at baseline and in 2004/2005. Cox regression with adjustment for major determinants for T2D was carried out to examine the influence of these types of activities on T2D risk. During 705,869 person years of follow-up, 3,491 incident T2D cases were documented. In multivariable adjusted models including aerobic MVPA, the pooled relative risk (RR) for T2D for women performing 1–29, 30–59, 60–150, and >150 min/week of total muscle-strengthening and conditioning activities was 0.83, 0.93, 0.75, and 0.60 compared to women reporting no muscle-strengthening and conditioning activities (p<0.001 for trend). Furthermore, resistance exercise and lower intensity muscular conditioning exercises were each independently associated with lower risk of T2D in pooled analyses. Women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening activities had substantial risk reduction compared with inactive women (pooled RR = 0.33 [95% CI 0.29–0.38]). Limitations to the study include that muscle-strengthening and conditioning activity and other types of physical activity were assessed by a self-administered questionnaire and that the study population consisted of registered nurses with mostly European ancestry.
Conclusions
Our study suggests that engagement in muscle-strengthening and conditioning activities (resistance exercise, yoga, stretching, toning) is associated with a lower risk of T2D. Engagement in both aerobic MVPA and muscle-strengthening type activity is associated with a substantial reduction in the risk of T2D in middle-aged and older women.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 370 million people have diabetes mellitus, a disorder characterized by poor glycemic control—dangerously high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas. In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing excess sugar from the blood become less responsive to insulin. Type 2 diabetes, which was previously known as adult-onset diabetes, can often initially be controlled with diet and exercise, and with antidiabetic drugs such as metformin and sulfonylureas. However, as the disease progresses, the pancreatic beta cells, which make insulin, become impaired and patients may eventually need insulin injections. Long-term complications of diabetes, which include an increased risk of cardiovascular problems such as heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
Type 2 diabetes is becoming increasingly common worldwide so better preventative strategies are essential. It is well-established that regular aerobic exercise—physical activity in which the breathing and heart rate increase noticeably such as jogging, brisk walking, and swimming—lowers the risk of type 2 diabetes. The World Health Organization currently recommends that adults should do at least 150 min/week of moderate-to-vigorous aerobic physical activity to reduce the risk of diabetes and other non-communicable diseases. It also recommends that adults should undertake muscle-strengthening and conditioning activities such as weight training and yoga on two or more days a week. However, although studies have shown that muscle-strengthening activity improves glycemic control in people who already have diabetes, it is unclear whether this form of exercise prevents diabetes. In this prospective cohort study (a study in which disease development is followed up over time in a group of people whose characteristics are recorded at baseline), the researchers investigated the association of muscle-strengthening activities with the risk of type 2 diabetes in women.
What Did the Researchers Do and Find?
The researchers followed up nearly 100,000 women enrolled in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII), two prospective US investigations into risk factors for chronic diseases in women, for 8 years. The women provided information on weekly participation in muscle-strengthening exercise (for example, weight training), lower intensity muscle-conditioning exercises (for example, yoga and toning), and aerobic moderate and vigorous physical activity (aerobic MVPA) at baseline and 4 years later. During the study 3,491 women developed diabetes. After allowing for major risk factors for type 2 diabetes (for example, diet and a family history of diabetes) and for aerobic MVPA, compared to women who did no muscle-strengthening or conditioning exercise, the risk of developing type 2 diabetes among women declined with increasing participation in muscle-strengthening and conditioning activity. Notably, women who did more than 150 min/week of these types of exercise had 40% lower risk of developing diabetes as women who did not exercise in this way at all. Muscle-strengthening and muscle-conditioning exercise were both independently associated with reduced diabetes risk, and women who engaged in at least 150 min/week of aerobic MVPA and at least 60 min/week of muscle-strengthening exercise were a third as likely to develop diabetes as inactive women.
What Do These Findings Mean?
These findings show that, among the women enrolled in NHS and NHSII, engagement in muscle-strengthening and conditioning activities lowered the risk of type 2 diabetes independent of aerobic MVPA. That is, non-aerobic exercise provided protection against diabetes in women who did no aerobic exercise. Importantly, they also show that doing both aerobic exercise and muscle-strengthening exercise substantially reduced the risk of type 2 diabetes. Because nearly all the participants in NHS and NHSII were of European ancestry, these results may not be generalizable to women of other ethnic backgrounds. Moreover, the accuracy of these findings may be limited by the use of self-administered questionnaires to determine how much exercise the women undertook. Nevertheless, these findings support the inclusion of muscle-strengthening and conditioning exercises in strategies designed to prevent type 2 diabetes in women, a conclusion that is consistent with current guidelines for physical activity among adults.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001587.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and explains the benefits of regular physical activity
The World Health Organization provides information about diabetes and about physical activity and health (in several languages); its 2010 Global Recommendations on Physical Activity for Health are available in several languages
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups; its Physical Activity for Everyone web pages include guidelines, instructional videos and personal success stories
More information about the Nurses Health Study and the Nurses Health Study II is available
The UK charity Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes and about physical exercise and fitness (in English and Spanish)
doi:10.1371/journal.pmed.1001587
PMCID: PMC3891575  PMID: 24453948
2.  Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running 
Background
The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid) metabolism.
Methods
Two groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW) were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG) concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations.
Results
Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE) of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P < 0.001) in order to meet their increased caloric requirement. Mean plasma insulin (P < 0.001) and FFA (P < 0.006) concentrations were lower in the exercise-trained rats as compared to sedentary controls. Mean steady state plasma insulin (SSPI) and glucose (SSPG) concentrations were not significantly different in sedentary control rats as compared to exercise-trained animals. Plantaris PGC-1α protein expression increased significantly from a 1.11 ± 0.12 in the sedentary rats to 1.74 ± 0.09 in exercising rats (P < 0.001). However, exercise had no effect on PGC-1α protein content in either soleus muscle or liver tissue. These results indicate that exercise training selectively up regulates the PGC-1α protein expression in high-oxidative fast skeletal muscle type such as plantaris muscle.
Conclusion
These data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity) and lowering of circulating FFA levels.
doi:10.1186/1743-7075-7-36
PMCID: PMC2874794  PMID: 20433743
3.  Chronic Exercise Increases Plasma Brain-Derived Neurotrophic Factor Levels, Pancreatic Islet Size, and Insulin Tolerance in a TrkB-Dependent Manner 
PLoS ONE  2014;9(12):e115177.
Background
Physical exercise improves glucose metabolism and insulin sensitivity. Brain-derived neurotrophic factor (BDNF) enhances insulin activity in diabetic rodents. Because physical exercise modifies BDNF production, this study aimed to investigate the effects of chronic exercise on plasma BDNF levels and the possible effects on insulin tolerance modification in healthy rats.
Methods
Wistar rats were divided into five groups: control (sedentary, C); moderate- intensity training (MIT); MIT plus K252A TrkB blocker (MITK); high-intensity training (HIT); and HIT plus K252a (HITK). Training comprised 8 weeks of treadmill running. Plasma BDNF levels (ELISA assay), glucose tolerance, insulin tolerance, and immunohistochemistry for insulin and the pancreatic islet area were evaluated in all groups. In addition, Bdnf mRNA expression in the skeletal muscle was measured.
Principal Findings
Chronic treadmill exercise significantly increased plasma BDNF levels and insulin tolerance, and both effects were attenuated by TrkB blocking. In the MIT and HIT groups, a significant TrkB-dependent pancreatic islet enlargement was observed. MIT rats exhibited increased liver glycogen levels following insulin administration in a TrkB-independent manner.
Conclusions/Significance
Chronic physical exercise exerted remarkable effects on insulin regulation by inducing significant increases in the pancreatic islet size and insulin sensitivity in a TrkB-dependent manner. A threshold for the induction of BNDF in response to physical exercise exists in certain muscle groups. To the best of our knowledge, these are the first results to reveal a role for TrkB in the chronic exercise-mediated insulin regulation in healthy rats.
doi:10.1371/journal.pone.0115177
PMCID: PMC4274083  PMID: 25531651
4.  Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats 
Islets  2010;2(4):240-246.
To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary. At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets.
doi:10.4161/isl.2.4.12266
PMCID: PMC3322538  PMID: 21099318
insulin secretion; exercise; anaerobic threshold; rats; glucose homeostasis
5.  Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans 
BMC Biology  2005;3:19.
Background
Regular exercise reduces cardiovascular and metabolic disease partly through improved aerobic fitness. The determinants of exercise-induced gains in aerobic fitness in humans are not known. We have demonstrated that over 500 genes are activated in response to endurance-exercise training, including modulation of muscle extracellular matrix (ECM) genes. Real-time quantitative PCR, which is essential for the characterization of lower abundance genes, was used to examine 15 ECM genes potentially relevant for endurance-exercise adaptation. Twenty-four sedentary male subjects undertook six weeks of high-intensity aerobic cycle training with muscle biopsies being obtained both before and 24 h after training. Subjects were ranked based on improvement in aerobic fitness, and two cohorts were formed (n = 8 per group): the high-responder group (HRG; peak rate of oxygen consumption increased by +0.71 ± 0.1 L min-1; p < 0.0001) while the low-responder group (LRG; peak rate of oxygen consumption did not change, +0.17 ± 0.1 L min-1, ns). ECM genes profiled included the angiopoietin 1 and related genes (angiopoietin 2, tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and 2 (TIE2), vascular endothelial growth factor (VEGF) and related receptors (VEGF receptor 1, VEGF receptor 2 and neuropilin-1), thrombospondin-4, α2-macroglobulin and transforming growth factor β2.
Results
neuropilin-1 (800%; p < 0.001) and VEGF receptor 2 (300%; p < 0.01) transcript abundance increased only in the HRG, whereas levels of VEGF receptor 1 mRNA actually declined in the LRG (p < 0.05). TIE1 and TIE2 mRNA levels were unaltered in the LRG, whereas transcription levels of both genes were increased by 2.5-fold in the HRG (p < 0.01). Levels of thrombospondin-4 (900%; p < 0.001) and α2-macroglobulin (300%, p < 0.05) mRNA increased substantially in the HRG. In contrast, the amount of transforming growth factor β2 transcript increased only in the HRG (330%; p < 0.01), whereas it remained unchanged in the LRG (-80%).
Conclusion
We demonstrate for the first time that aerobic training activates angiopoietin 1 and TIE2 genes in human muscle, but only when aerobic capacity adapts to exercise-training. The fourfold-greater increase in aerobic fitness and markedly differing gene expression profile in the HRG indicates that these ECM genes may be critical for physiological adaptation to exercise in humans. In addition, we show that, without careful demonstration of physiological adaptation, conclusions derived from gene expression profiling of human skeletal muscle following exercise may be of limited value. We propose that future studies should (a) investigate the mechanisms that underlie the apparent link between physiological adaptation and gene expression and (b) use the genes profiled in this paper as candidates for population genetic studies.
doi:10.1186/1741-7007-3-19
PMCID: PMC1224855  PMID: 16138928
6.  Exercise training improves sleep pattern and metabolic profile in elderly people in a time-dependent manner 
Aging and physical inactivity are two factors that favors the development of cardiovascular disease, metabolic syndrome, obesity, diabetes, and sleep dysfunction. In contrast, the adoption a habitual of moderate exercise may present a non-pharmacological treatment alternative for sleep and metabolic disorders. We aimed to assess the effects of moderate exercise training on sleep quality and on the metabolic profile of elderly people with a sedentary lifestyle. Fourteen male sedentary, healthy, elderly volunteers performed moderate training for 60 minutes/day, 3 days/week for 24 wk at a work rate equivalent to the ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2°C, with an air humidity 60 ± 5%. Blood and polysomnographs analysis were collected 3 times: at baseline (1 week before training began), 3 and 6 months (after 3 and 6 months of training). Training promoted increasing aerobic capacity (relative VO2, time and velocity to VO2max; p < 0.05), and reduced serum NEFA, and insulin concentrations as well as improved HOMA index (p < 0.05), and increased adiponectin levels (p < 0.05), after 3 months of training when compared with baseline data. The sleep parameters, awake time and REM sleep latency were decreased after 6 months exercise training (p < 0.05) in relation baseline values. Our results demonstrate that the moderate exercise training protocol improves the sleep profile in older people, but the metabolism adaptation does not persist. Suggesting that this population requires training strategy modifications as to ensure consistent alterations regarding metabolism.
doi:10.1186/1476-511X-10-113
PMCID: PMC3154859  PMID: 21733182
aerobic capacity; sleep; metabolism; moderate training
7.  Effects of Low-Volume High-Intensity Interval Training (HIT) on Fitness in Adults: A Meta-Analysis of Controlled and Non-Controlled Trials 
Sports Medicine (Auckland, N.z.)  2014;44(7):1005-1017.
Background
Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness.
Objective
Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO2max] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test).
Data Sources
Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included ‘high intensity’, ‘HIT’, ‘sprint’, ‘fitness’ and ‘VO2max’.
Study Selection
Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30–60 s; work/rest ratio <1.0; exercise intensity described as maximal or near maximal; adult subjects aged >18 years.
Data Extraction
The final data set consisted of 55 estimates from 32 trials for VO2max, 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness.
Results
A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO2max of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO2max of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a likely small increase for sedentary females (7.3 %; ±4.8 %). The effect on the VO2max of athletic males was unclear (2.7 %; ±4.6 %). A possibly moderate additional increase was likely for subjects with a 10 mL·kg−1·min−1 lower baseline VO2max (3.8 %; ±2.5 %), whereas the modifying effects of sex and difference in exercise dose were unclear. The comparison of HIT with traditional endurance training was unclear (−1.6 %; ±4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta-analysed effects of HIT on Wingate peak and mean power were unclear.
Conclusions
Low-volume HIT produces moderate improvements in the aerobic power of active non-athletic and sedentary subjects. More studies are needed to resolve the unclear modifying effects of sex and HIT dose on aerobic power and the unclear effects on sprint fitness.
doi:10.1007/s40279-014-0180-z
PMCID: PMC4072920  PMID: 24743927
8.  Similar Health Benefits of Endurance and High-Intensity Interval Training in Obese Children 
PLoS ONE  2012;7(8):e42747.
Purpose
To compare two modalities of exercise training (i.e., Endurance Training [ET] and High-Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years.
Methods
Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last ∼70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed.
Results
Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO2 peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups.
Conclusion
HIT and ET were equally effective in improving important health related parameters in obese youth.
doi:10.1371/journal.pone.0042747
PMCID: PMC3412799  PMID: 22880097
9.  Aerobic exercise training increases circulating IGFBP-1 concentration, but does not attenuate the reduction in circulating IGFBP-1 after a high-fat meal 
Metabolism  2011;61(3):310-316.
Rationale
Insulin-like growth factor binding protein-1 (IGFBP-1) has metabolic effects throughout the body and its expression is regulated in part by insulin. Circulating IGFBP-1 predicts development of cardiometabolic diseases in longitudinal studies and low IGFBP-1 concentrations are associated with insulin resistance and consumption of a high-fat diet. Because of the favorable metabolic effects of regular aerobic exercise, we hypothesized that aerobic exercise training would increase plasma IGFBP-1 concentrations and attenuate the reduction in IGFBP-1 after a high-fat meal.
Methods
Ten overweight (BMI=28.7±0.9kg/m2), older (61±2yr) men and women underwent high-fat feeding and oral glucose tolerance tests (OGTT) at baseline and after 6 months of aerobic exercise training.
Results
In response to aerobic exercise training, subjects increased cardiorespiratory fitness 13% (p<0.05) and insulin sensitivity index 28% (p<0.05). Basal plasma concentrations of IGFBP-1 increased 41% after aerobic exercise training (p<0.05). The insulin response to an OGTT was a significant predictor of fasting plasma IGFBP-1 concentrations at baseline and after exercise training (p=0.02). In response to the high-fat meal at baseline, plasma IGFBP-1 concentrations decreased 58% (p<0.001); a 61% decrease to similar postprandial concentrations was observed after exercise training (p<0.001). Plasma insulin response to the high-fat meal was inversely associated with postprandial IGFBP-1 concentrations at baseline and after exercise training (p=0.06 and p<0.05, respectively).
Conclusion
While aerobic exercise training did not attenuate the response to a high-fat meal, the increase in IGFBP-1 concentrations after exercise training may be one mechanism by which exercise reduces risk for cardiometabolic diseases in older adults.
doi:10.1016/j.metabol.2011.07.003
PMCID: PMC3227769  PMID: 21872284
insulin; glucose tolerance; lipemia; diet
10.  High- and Moderate-Intensity Training Normalizes Ventricular Function and Mechanoenergetics in Mice With Diet-Induced Obesity 
Diabetes  2013;62(7):2287-2294.
Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8–10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders.
doi:10.2337/db12-1580
PMCID: PMC3712042  PMID: 23493573
11.  Reducing the Intensity and Volume of Interval Training Diminishes Cardiovascular Adaptation but Not Mitochondrial Biogenesis in Overweight/Obese Men 
PLoS ONE  2013;8(7):e68091.
Objective
The purpose of this research was to determine if the adaptations to high intensity interval training (HIT) are mitigated when both intensity and training volume (i.e. exercise energy expenditure) are reduced.
Methods
19 overweight/obese, sedentary males (Age: 22.7±3.9 yrs, Body Mass Index: 31.4±2.6 kg/m2, Waist Circumference: 106.5±6.6 cm) performed 9 sessions of interval training using a 1-min on, 1-min off protocol on a cycle ergometer over three weeks at either 70% (LO) or 100% (HI) peak work rate.
Results
Cytochrome oxidase I protein content, cytochrome oxidase IV protein content, and citrate synthase maximal activity all demonstrated similar increases between groups with a significant effect of training for each. β-hydroxyacyl-CoA dehydrogenase maximal activity tended to increase with training but did not reach statistical significance (p = 0.07). Peroxisome proliferator-activated receptor gamma coactivator-1α and silent mating type information regulator 2 homolog 1 protein contents also increased significantly (p = 0.047), while AMP-activated protein kinase protein content decreased following the intervention (p = 0.019). VO2peak increased by 11.0±7.4% and 27.7±4.4% in the LO and HI groups respectively with significant effects of both training (p<0.001) and interaction (p = 0.027). Exercise performance improved by 8.6±7.6% in the LO group and 14.1±4.3% in the HI group with a significant effect of training and a significant difference in the improvement between groups. There were no differences in perceived enjoyment or self-efficacy between groups despite significantly lower affect scores during training in the HI group.
Conclusions
While improvements in aerobic capacity and exercise performance were different between groups, changes in oxidative capacity were similar despite reductions in both training intensity and volume.
doi:10.1371/journal.pone.0068091
PMCID: PMC3702554  PMID: 23861854
12.  Physical exercise and pancreatic islets 
Islets  2012;4(4):296-301.
Diabetes mellitus (DM) is a great public health problem, which attacks part of the world population, being characterized by an imbalance in body glucose homeostasis. Physical exercise is pointed as a protective agent and is also recommended to people with DM. As pancreatic islets present an important role in glucose homeostasis, we aim to study the role of physical exercise (chronic adaptations and acute responses) in pancreatic islets functionality in Wistar male rats. First, animals were divided into two groups: sedentary (S) and aerobic trained (T). At the end of 8 weeks, half of them (S and T) were submitted to an acute exercise session (exercise until exhaustion), being subdivided as acute sedentary (AS) and acute trained (AT). After the experimental period, periepididymal, retroperitoneal and subcutaneous fat pads, blood, soleus muscle and pancreatic islets were collected and prepared for further analysis. From the pancreatic islets, total insulin content, insulin secretion stimulated by glucose, leucine, arginine and carbachol were analyzed. Our results pointed that body adiposity and glucose homeostasis improved with chronic physical exercise. In addition, total insulin content was reduced in group AT, insulin secretion stimulated by glucose was reduced in trained groups (T and AT) and insulin secretion stimulated by carbachol was increased in group AT. There were no significant differences in insulin secretion stimulated by arginine and leucine. We identified a possible modulating action on insulin secretion, probably related to the association of chronic adaptation with an acute response on cholinergic activity in pancreatic islets.
doi:10.4161/isl.21273
PMCID: PMC3496654  PMID: 22868676
exercise; islets; chronic adaptations; acute response; glucose homeostasis
13.  Exercise training with weight loss and either a high or low glycemic diet reduces metabolic syndrome severity in older adults 
Annals of nutrition & metabolism  2012;61(2):135-141.
Background
The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low or high glycemic diet on metabolic syndrome severity (Z-score).
Methods
Twenty-one adults (66.2 ± 1.1 yr; BMI = 35.3 ± 0.9 kg/m2) with metabolic syndrome were randomized to 12 weeks of exercise (60 minutes/d for 5 d/week at ~85% HRmax) and provided a low-glycemic (n=11; LoGIx) or high glycemic (n=10; HiGIx) diet. Z-scores were determined from: blood pressure, triglycerides (TG), high-density lipoproteins (HDL), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and non-esterfied fatty acid (NEFA) suppression were also assessed.
Results
LoGIx and HiGIx decreased body mass and insulin resistance and increased aerobic fitness comparably (p < 0.05). LoGIx and HiGIx decreased the Z-score similarly, as each intervention decreased blood pressure, TG, FPG, and WC (p < 0.05). HiGIx tended to suppress NEFA during insulin stimulation compared to LoGIx (p = 0.06).
Conclusions
Our findings highlight that exercise with weight loss reduces metabolic syndrome severity whether individuals were randomized to a high or low glycemic index diet.
doi:10.1159/000342084
PMCID: PMC3586384  PMID: 23036993
aging; obesity; lifestyle modification; diabetes; impaired glucose tolerance
14.  Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations 
Background
Elevated non-esterified fatty acids (NEFA) concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL), 105 and 135 days gestational age (dGA, term 147+/- 3 days).
Methods
The plasma concentrations of insulin, growth hormone (GH) and ovine placental lactogen (oPL) were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA.
Results
Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC) profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p < 0.001 and P < 0.001, respectively). In hyperglycaemic clamp studies, while maintaining glucose levels not different from NPNL ewes, pregnant ewes displayed significantly reduced insulin responses and a maintained depressed insulin secretion. In NPNL ewes, 105 and 135 dGA ewes, the Glucose Infusion Rate (GIR) was constant at approximately 5.8 mg glucose/kg/min during the last 40 minutes of the hyperglycaemic clamp and the Mean Plasma Insulin Increment (MPII) was only significantly (p < 0.001) greater in NPNL ewes. Following the clamp, NEFA concentrations were reduced by approximately 60% of pre-clamp levels in all groups, though a blunted and suppressed insulin response was maintained in 105 and 135 dGA ewes.
Conclusions
Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones of pregnancy and possibly NEFA metabolism, may act to maintain a reduced insulin output, thereby sparing glucose for non-insulin dependent placental uptake and ultimately, fetal requirements.
doi:10.1186/1477-7827-2-64
PMCID: PMC519029  PMID: 15352999
15.  Lower Dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome 
Peptides  2013;47:10.1016/j.peptides.2013.07.008.
Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2yr, BMI: 34.2±1.1kg/m2) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60 min/d for 5 d/wk at ~85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m2/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-hour glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P<0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P<0.001) and decreased HOMA-IR by 15% (P<0.05). Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=−0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=−0.54; P<0.05). Increased fat oxidation also correlated with lower 2-hour glucose levels (r=−0.64; P<0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome.
doi:10.1016/j.peptides.2013.07.008
PMCID: PMC3825405  PMID: 23872069
impaired glucose tolerance; obesity; cytokine; diabetes
16.  A Practical Model of Low-Volume High-Intensity Interval Training Induces Performance and Metabolic Adaptations That Resemble ‘All-Out’ Sprint Interval Training 
Recently, a novel type of high-intensity interval training known as sprint interval training has demonstrated increases in aerobic and anaerobic performance with very low time commitment. However, this type of training program is unpractical for general populations. The present study compared the impact of a low-volume high-intensity interval training to a "all-out" sprint interval training. Twenty-four active young males were recruited and randomized into three groups: (G1: 3-5 cycling bouts ˟ 30-s all-out with 4 min recovery; G2: 6- 10 cycling bouts ˟ 125% Pmax with 2 min recovery) and a non-trained control group. They all performed a VO2max test, a time to exhaustion at Pmax (Tmax) and a Wingate test before and after the intervention. Capillary blood lactate was taken at rest, 3, and 20 min after the Wingate trial. Training was performed 3 sessions per week for 4 weeks. In G1, significant improvements (p < 0.05) following training were found in VO2max (9.6%), power at VO2max (12.8%), Tmax (48.4%), peak power output (10.3%) and mean power output (17.1%). In G2, significant improvements following training were found in VO2max (9.7%), power at VO2max (16.1%), Tmax (54.2%), peak power output (7.4%; p < 0.05), but mean power output did not change significantly. Blood lactate recovery (20th min) significantly decreased in G1 and G2 when compared with pre-testing and the CON group (p < 0.05). In conclusion, the results of the current study agree with earlier work demonstrating the effectiveness of 30-s all-out training program to aerobic and anaerobic adaptations. Of substantial interest is that the low volume high intensity training provides similar results but involves only half the intensity with double the repetitions.
Key pointsGiven the markedly lower training volume in the training groups, our results suggest that intense interval training is indeed a time-efficient strategy to induce rapid metabolic and performance adaptations.The results demonstrate that a practical low-volume HIT program is effective for improving metabolic and performance adaptations that resemble many of the same performance gains occurred in all-out SIT protocol.
PMCID: PMC3737829  PMID: 24150635
Wingate test; repeated sprints; blood lactate; training adaptations.
17.  Hemoglobin A1c Levels and Risk of Severe Hypoglycemia in Children and Young Adults with Type 1 Diabetes from Germany and Austria: A Trend Analysis in a Cohort of 37,539 Patients between 1995 and 2012 
PLoS Medicine  2014;11(10):e1001742.
In a cohort study, Beate Karges and colleagues find that the association between low hemoglobin A1C and severe hypoglycemia in children and young adults with type 1 diabetes has decreased over the period between 1995 and 2012.
Please see later in the article for the Editors' Summary
Background
Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years.
Methods and Findings
We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4±3.8 y, range 1–20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19–1.37) to 1.05 (1.00–1.09) and from 1.39 (1.23–1.56) to 1.01 (0.93–1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6–1.7, p<0.001) and 1.9% (0.8–2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%–6.9% (RR 0.96 and 0.90 each year) and 7.0%–7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study.
Conclusions
The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 380 million people have diabetes, a chronic disorder characterized by high levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone produced by the pancreas. In people with diabetes, blood sugar control fails because they make no insulin (type 1 diabetes) or because the cells that normally respond to insulin by removing sugar from the blood have become insulin-resistant (type 2 diabetes). Type 1 diabetes, which tends to develop in childhood or early adulthood, is responsible for about 10% of cases of diabetes in adults and is treated with injections of insulin. Type 2 diabetes can usually be treated with diet, exercise, and antidiabetic drugs. With both types of diabetes, it is important to keep blood sugar levels within the normal range (good glycemic control) to reduce the long-term complications of diabetes, which include kidney failure, blindness, and an increased risk of cardiovascular disease.
Why Was This Study Done?
Patients with type 1 diabetes can achieve strict glycemic control using intensive insulin therapy, but such treatment is associated with a risk of severe or fatal hypoglycemia (low blood sugar). Past studies have found an association between low levels of hemoglobin A1c (HbA1c, a marker of average blood sugar levels over the past 2–3 months; a low HbA1c percentage indicates good glycemic control) and a high risk of severe hypoglycemia. Because of this inverse association, people at risk of severe hypoglycemia are advised to aim for an HbA1c of 7.5% or less, which puts them at risk of diabetic complications (most adults with diabetes aim for an HbA1c of 6.5% or less; people without diabetes have Hb1Ac readings below 6.05%). With recent improvements in insulin therapy, it is not clear whether the inverse association between the incidence of severe hypoglycemia and HbA1c levels still exists. In this trend analysis, the researchers investigate the association over time between HbA1C levels and the risk of severe hypoglycemia in a large cohort (group) of Austrian and German children and young adults with type 1 diabetes.
What Did the Researchers Do and Find?
The researchers analyzed data on Hb1Ac levels and on incidents of severe hypoglycemia and hypoglycemic coma collected from 37,539 children and young adults with type 1 diabetes between 1995 and 2012 by the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative for diabetes care. The DPV cohort includes around 80% of all children and young adults with type 1 diabetes in Germany and Austria. Over the study period, the use of insulin analogs (compounds related to insulin that keep blood sugar levels steadier than regular insulin injections) and of insulin pumps (which deliver constant amounts of short-acting insulin analogs to the body) increased, and there was an increase in how often patients monitored their blood sugar level. Notably, between 1995 and 2012, the relative risk for severe hypoglycemia per 1% decrease in Hb1Ac declined from 1.28 to 1.05, and the relative risk for hypoglycemic coma per 1% decrease in Hb1Ac declined from 1.39 to 1.01. That is, the strength of the inverse association between severe hypoglycemia or coma and HbA1c decreased during the study period. Expressed another way, between 1995 and 2012, the relative risk for severe hypoglycemia and coma per 1% HbA1c decrease dropped by 1.2% and 1.9%, respectively, each year.
What Do These Findings Mean?
These findings reveal a substantial decrease since 1995 in the previously strong inverse association between low HbA1c levels and severe hypoglycemia and hypoglycemic coma in this cohort of young Germans and Austrians with type 1 diabetes. This decrease mainly occurred because of substantial reductions in the risk of hypoglycemia in patients with HbA1c levels between 6.0% and 7.9%, but the study provides no information about the drivers of this reduction. Moreover, these findings may apply only to young type 1 diabetes patients of European descent, and their accuracy may be limited by other aspects of the study design. However, by showing that HbA1c has become a minor predictor for severe hypoglycemia in this group of patients, these findings suggest that strict glycemic control in young patients with type 1 diabetes has become safer in recent years. Thus, it should now be possible to reduce the risk of long-term diabetic complications in such patients through achievement of near-normal glycemic control without increasing patients' risk of severe hypoglycemia.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001742.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public (in English and Spanish), including information on the HbA1c test and a description of a trial that compared the effects of intensive versus conventional treatment of blood glucose levels on the development of diabetic complications in patients with type 1 diabetes
The UK National Health Service Choices website provides information for patients and carers about type 1 diabetes, including a video that describes parents' experiences caring for a child with type 1 diabetes, and information about treating type 1 diabetes that includes a short video about HbA1c
The charity Diabetes UK provides detailed information about type 1 diabetes for patients and carers
The UK-based non-profit organization Healthtalkonline provides information about type 1 diabetes and young people, including interviews with young people about their experiences of the condition
MedlinePlus provides links to further resources and advice about type 1 diabetes (in English and Spanish)
Information about the DPV Initiative is available (mainly in German)
doi:10.1371/journal.pmed.1001742
PMCID: PMC4188517  PMID: 25289645
18.  Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. 
Journal of Clinical Investigation  1991;88(4):1282-1290.
Increased nonesterified fatty acid (NEFA) levels may be important in causing insulin resistance in skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of the antilipolytic nicotinic acid analogue Acipimox (2 X 250 mg) on basal and insulin-stimulated (3 h, 40 mU/m2 per min) glucose metabolism was therefore studied in 12 patients with NIDDM. Whole-body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated steady-state periods. Acipimox reduced NEFA in the basal state and during insulin stimulation. Lipid oxidation was inhibited by Acipimox in all patients in the basal state (20 +/- 2 vs. 33 +/- 3 mg/m2 per min, P less than 0.01) and during insulin infusion (8 +/- 2 vs. 17 +/- 2 mg/m2 per min, P less than 0.01). Acipimox increased the insulin-stimulated glucose disposal rate (369 +/- 49 vs. 262 +/- 31 mg/m2 per min, P less than 0.01), whereas the glucose disposal rate was unaffected by Acipimox in the basal state. Acipimox increased glucose oxidation in the basal state (76 +/- 4 vs. 50 +/- 4 mg/m2 per min, P less than 0.01). During insulin infusion Acipimox increased both glucose oxidation (121 +/- 7 vs. 95 +/- 4 mg/m2 per min, P less than 0.01) and nonoxidative glucose disposal (248 +/- 47 vs. 167 +/- 29 mg/m2 per min, P less than 0.01). Acipimox enhanced basal and insulin-stimulated muscle fractional glycogen synthase activities (32 +/- 2 vs. 25 +/- 3%, P less than 0.05, and 50 +/- 5 vs. 41 +/- 4%, P less than 0.05). Activities of muscle pyruvate dehydrogenase and phosphofructokinase were unaffected by Acipimox. In conclusion, Acipimox acutely improved insulin action in patients with NIDDM by increasing both glucose oxidation and nonoxidative glucose disposal. This supports the hypothesis that elevated NEFA concentrations may be important for the insulin resistance in NIDDM. The mechanism responsible for the increased insulin-stimulated nonoxidative glucose disposal may be a stimulatory effect of Acipimox on glycogen synthase activity in skeletal muscles.
Images
PMCID: PMC295597  PMID: 1918378
19.  High Intensity Interval Training in a Real World Setting: A Randomized Controlled Feasibility Study in Overweight Inactive Adults, Measuring Change in Maximal Oxygen Uptake 
PLoS ONE  2014;9(1):e83256.
Background
In research clinic settings, overweight adults undertaking HIIT (high intensity interval training) improve their fitness as effectively as those undertaking conventional walking programs but can do so within a shorter time spent exercising. We undertook a randomized controlled feasibility (pilot) study aimed at extending HIIT into a real world setting by recruiting overweight/obese, inactive adults into a group based activity program, held in a community park.
Methods
Participants were allocated into one of three groups. The two interventions, aerobic interval training and maximal volitional interval training, were compared with an active control group undertaking walking based exercise. Supervised group sessions (36 per intervention) were held outdoors. Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake, results expressed in ml/min/kg), before and after the 12 week interventions.
Results
On ITT (intention to treat) analyses, baseline (N = 49) and exit (N = 39) O2 was 25.3±4.5 and 25.3±3.9, respectively. Participant allocation and baseline/exit VO2max by group was as follows: Aerobic interval training N =  16, 24.2±4.8/25.6±4.8; maximal volitional interval training N = 16, 25.0±2.8/25.2±3.4; walking N = 17, 26.5±5.3/25.2±3.6. The post intervention change in VO2max was +1.01 in the aerobic interval training, −0.06 in the maximal volitional interval training and −1.03 in the walking subgroups. The aerobic interval training subgroup increased VO2max compared to walking (p = 0.03). The actual (observed, rather than prescribed) time spent exercising (minutes per week, ITT analysis) was 74 for aerobic interval training, 45 for maximal volitional interval training and 116 for walking (p =  0.001). On descriptive analysis, the walking subgroup had the fewest adverse events.
Conclusions
In contrast to earlier studies, the improvement in cardiorespiratory fitness in a cohort of overweight/obese participants undertaking aerobic interval training in a real world setting was modest. The most likely reason for this finding relates to reduced adherence to the exercise program, when moving beyond the research clinic setting.
Trial Registration
ACTR.org.au ACTRN12610000295044
doi:10.1371/journal.pone.0083256
PMCID: PMC3890270  PMID: 24454698
20.  Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals 
Diabetes Care  2009;32(12):2161-2167.
OBJECTIVE
To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations.
RESEARCH DESIGN AND METHODS
Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period.
RESULTS
Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001).
CONCLUSIONS
Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals.
doi:10.2337/dc08-1994
PMCID: PMC2782969  PMID: 19729520
21.  Sex-Related Differences in the Effects of the Mediterranean Diet on Glucose and Insulin Homeostasis 
Objective. To document sex differences in the impact of the Mediterranean diet (MedDiet) on glucose/insulin homeostasis and to verify whether these sex-related effects were associated with changes in nonesterified fatty acids (NEFA). Methods. All foods were provided to 38 men and 32 premenopausal women (24–53 y) during 4 weeks. Variables were measured during a 180 min OGTT before and after the MedDiet. Results. A sex-by-time interaction for plasma insulin iAUC was found (men: −17.8%, P = 0.02; women: +9.4%, P = 0.63; P for sex-by-time interaction = 0.005). A sex-by-time interaction was also observed for insulin sensitivity (Cederholm index, P = 0.03), for which only men experienced improvements (men: +8.1%, P = 0.047; women: −5.9%, P = 0.94). No sex difference was observed for glucose and C-peptide responses. Trends toward a decrease in NEFA AUC (P = 0.06) and an increase in NEFA suppression rate (P = 0.06) were noted, with no sex difference. Changes in NEFA were not associated with change in insulin sensitivity. Conclusions. Results suggest that the more favorable changes in glucose/insulin homeostasis observed in men compared to women in response to the MedDiet are not explained by sex differences in NEFA response. This clinical trial is registered with clinicaltrials.gov NCT01293344.
doi:10.1155/2014/424130
PMCID: PMC4209833  PMID: 25371817
22.  High Intensity Training Improves Health and Physical Function in Middle Aged Adults 
Biology  2014;3(2):333-344.
High intensity training (HIT) is effective at improving health; however, it is unknown whether HIT also improves physical function. This study aimed to determine whether HIT improves metabolic health and physical function in untrained middle aged individuals. Fourteen (three male and eleven female) untrained individuals were recruited (control group n = 6: age 42 ± 8 y, weight 64 ± 10 kg, BMI 24 ± 2 kg·m−2 or HIT group n = 8: age 43 ± 8 y, weight 80 ± 8 kg, BMI 29 ± 5 kg·m−2). Training was performed twice weekly, consisting of 10 × 6-second sprints with a one minute recovery between each sprint. Metabolic health (oral glucose tolerance test), aerobic capacity (incremental time to exhaustion on a cycle ergometer) and physical function (get up and go test, sit to stand test and loaded 50 m walk) were determined before and after training. Following eight weeks of HIT there was a significant improvement in aerobic capacity (8% increase in VO2 peak; p < 0.001), physical function (11%–27% respectively; p < 0.05) and a reduction in blood glucose area under the curve (6% reduction; p < 0.05). This study demonstrates for the first time the potential of HIT as a training intervention to improve skeletal muscle function and glucose clearance as we age.
doi:10.3390/biology3020333
PMCID: PMC4085611  PMID: 24833513
VO2 peak; oral glucose tolerance; functional capacity; middle age
23.  Responses of young girls to two modes of aerobic training. 
OBJECTIVES: To investigate the physiological effects of two different three times a week, eight week training programmes on the aerobic fitness of nine to ten year old girls. METHODS: Treadmill determined peak VO2, submaximal heart rates, and submaximal blood lactate were the criterion measures. Seventeen girls completed a programme of "aerobics" training where sessions lasted 20-25 minutes. Eighteen girls followed a cycle ergometer training programme which involved pedalling continuously for 20 minutes with the heart rate maintained between 160 and 170 beats/minute. A control group of 16 girls completed the criterion tests but did not train. In the cycle ergometer group and eight control subjects plasma total cholesterol and high density lipoprotein cholesterol were determined before and after training. RESULTS: Peak VO2 did not change significantly with training in either training group, neither were there any significant changes in submaximal heart rates. Blood lactate declined significantly at the two lowest submaximal exercise intensities in the cycle ergometer training group (from 2.3 (1.1) to 1.4 (0.06) mmol/l at stage 1 and from 2.1 (1.2) to 1.6 (0.06) mmol/l at stage 2; means (SD); P < 0.01). Total cholesterol and high density lipoprotein cholesterol remained unchanged with training. CONCLUSIONS: These findings suggest that an eight week structured exercise programme produces minimal changes in either the aerobic fitness or blood lipids of young girls. It may be more beneficial for long term health to promote enjoyment in activity and positive attitudes to exercise rather than attempting to enhance aerobic fitness through strenuous exercise programmes.
PMCID: PMC1332614  PMID: 9192129
24.  Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training 
The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type.
doi:10.5717/jenb.2013.17.4.209
PMCID: PMC4241911  PMID: 25566432
Fatty acid binding protein 2 gene; aerobic exercise; obesity index; biochemical variable; polymorphism; middle-aged women
25.  Exercise Training during Normobaric Hypoxic Confinement Does Not Alter Hormonal Appetite Regulation 
PLoS ONE  2014;9(6):e98874.
Background
Both exposure to hypoxia and exercise training have the potential to modulate appetite and induce beneficial metabolic adaptations. The purpose of this study was to determine whether daily moderate exercise training performed during a 10-day exposure to normobaric hypoxia alters hormonal appetite regulation and augments metabolic health.
Methods
Fourteen healthy, male participants underwent a 10-day hypoxic confinement at ∼4000 m simulated altitude (FIO2 = 0.139±0.003%) either combined with daily moderate intensity exercise (Exercise group; N = 8, Age = 25.8±2.4 yrs, BMI = 22.9±1.2 kg·m−2) or without any exercise (Sedentary group; N = 6 Age = 24.8±3.1 yrs, BMI = 22.3±2.5 kg·m−2). A meal tolerance test was performed before (Pre) and after the confinement (Post) to quantify fasting and postprandial concentrations of selected appetite-related hormones and metabolic risk markers. 13C-Glucose was dissolved in the test meal and 13CO2 determined in breath samples. Perceived appetite ratings were obtained throughout the meal tolerance tests.
Results
While body mass decreased in both groups (−1.4 kg; p = 0.01) following the confinement, whole body fat mass was only reduced in the Exercise group (−1.5 kg; p = 0.01). At Post, postprandial serum insulin was reduced in the Sedentary group (−49%; p = 0.01) and postprandial plasma glucose in the Exercise group (−19%; p = 0.03). Fasting serum total cholesterol levels were reduced (−12%; p = 0.01) at Post in the Exercise group only, secondary to low-density lipoprotein cholesterol reduction (−16%; p = 0.01). No differences between groups or testing periods were noted in fasting and/or postprandial concentrations of total ghrelin, peptide YY, and glucagon-like peptide-1, leptin, adiponectin, expired 13CO2 as well as perceived appetite ratings (p>0.05).
Conclusion
These findings suggest that performing daily moderate intensity exercise training during continuous hypoxic exposure does not alter hormonal appetite regulation but can improve the lipid profile in healthy young males.
doi:10.1371/journal.pone.0098874
PMCID: PMC4041840  PMID: 24887106

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