Aerobic exercise and resistance training for the management of type 2 diabetes mellitus

BACKGROUND
Implementation of a structured physical exercise program can improve glycemic control in patients with type 2 diabetes mellitus.

OBJECTIVE
To evaluate the efficacy of aerobic exercise and resistance training (either alone or in combination) in the management of type 2 diabetes mellitus.

DESIGN AND INTERVENTION
DARE (Diabetes Aerobic and Resistance Exercise) was a 26-week, single-center, parallel-group, randomized, controlled trial of patients with type 2 diabetes mellitus of >6 months' duration. Participants were aged 39-70 years with a baseline [HbA.sub.1c] level 6.6-9.9%. Exclusion criteria included current insulin therapy, regular exercise regime and blood pressure >160/95 mmHg. All participants underwent a 4-week run-in period that comprised 12 sessions of combined aerobic exercise and resistance training; participants who attended [greater than or equal to] 10 sessions were eligible to enter the study. Eligible participants were randomly allocated to one of four groups: aerobic exercise alone; resistance training alone; combined aerobic exercise and resistance training; and no intervention (control group). Exercise was performed three times weekly. The aerobic exercise group progressed from 15-20 min on a treadmill or bicycle ergometer per session at 60% of the maximum heart rate to 45 min per session at 75% of the maximum heart rate. The resistance training group performed 7 different exercises on weight machines per 45 min session, and progressed to 2-3 sets of each exercise at the maximum weight that could be lifted 7-9 times. The combined exercise group performed the full aerobic exercise program plus the full resistance training program. Participants in the control group reverted to their pre-study exercise levels.

OUTCOME MEASURES
The primary outcome measure was the change in [HbA.sub.1c] from baseline. Secondary outcome measures included changes in blood pressure, lipid profile, and body composition.

RESULTS
A total of 251 participants were eligible for intervention. The median session attendance was 80% (aerobic exercise), 85% (resistance training) and 86% (combined exercise). When compared with the control group, the HbA1c levels were reduced by 0.50% in the aerobic exercise group (P = 0.007) and by 0.38% in the resistance training group (P = 0.038). The combined exercise group had an additional reduction of 0.46% when compared with the aerobic exercise group (P = 0.014) and of 0.59% when compared with the resistance training group (P = 0.001). Decreases in [HbA.sub.1c] levels were greatest for participants with a baseline [HbA.sub.1c] level = 7.5% (P <0.001). For participants with a baseline level [HbA.sub.1c] <7.5%, significant improvements in glycemic control were observed in the combined exercise group only (P = 0.002). Changes in blood pressure and lipid profiles did not differ between the groups. By contrast, participation in a structured exercise program improved body composition.

CONCLUSION
Although aerobic exercise or resistance training alone improved glycemic control, additional improvements were observed with the combined exercise regimen.

Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 × 30 min of stationary cycling at 70% of their peak aerobic power (V̇O2,peak) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in V̇O2,peak (3.1 ± 0.16 to 3.6 ± 0.15 l min−1, P < 0.05) and endurance capacity (93 ± 8 to 168 ± 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in V̇O2,peak and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.

A randomised controlled trial investigating the effects of Mediterranean diet and aerobic exercise on cognition in cognitively healthy older people living independently within aged care facilities: The Lifestyle Intervention in Independent Living Aged Car

Background: The rapid ageing of the population is becoming an area of great concern, both globally and in Australia. On a societal level, the cost of supporting an ageing demographic, particularly with their associated medical requirements, is becoming an ever increasing burden that is only predicted to rise in the foreseeable future. The progressive decline in individuals' cognitive ability as they age, particularly with respect to the ever increasing incidence of Alzheimer's Disease (AD) and other cognitive complications, is in many respects one of the foundation stones of these concerns. There have been numerous observational studies reporting on the positive effects that aerobic exercise and the Mediterranean diet appear to have on improving cognitive ability. However, the ability of such interventions to improve cognitive ability, or even reduce the rate of cognitive ageing, has not been fully examined by substantial interventional studies within an ageing population. Methods: The LIILAC trial will investigate the potential for cognitive change in a cohort of cognitively healthy individuals, between the ages of 60 and 90 years, living in independent accommodation within Australian aged care facilities. This four-arm trial will investigate the cognitive changes which may occur as a result of the introduction of aerobic exercise and/or Mediterranean diet into individuals' lifestyles, as well as the mechanisms by which these changes may be occurring. Participants will be tested at baseline and 6 months on a battery of computer based cognitive assessments, together with cardiovascular and blood biomarker assessments. The cardiovascular measures will assess changes in arterial stiffness and central pulse pressures, while the blood measures will examine changes in metabolic profiles, including brain derived neurotrophic factor (BDNF), inflammatory factors and insulin sensitivity. Conclusion: It is hypothesised that exercise and Mediterranean diet interventions, both individually and in combination, will result in improvements in cognitive performance compared with controls. Positive findings in this research will have potential implications for the management of aged care, particularly in respect to reducing the rate of cognitive decline and the associated impacts both on the individual and the broader community.

Cerebral responses to innocuous somatic pressure stimulation following aerobic exercise rehabilitation in chronic pain patients: a functional magnetic resonance imaging study

Objective: The purpose of this research was to assess the functional brain activity and perceptual rating of innocuous somatic pressure stimulation before and after exercise rehabilitation in patients with chronic pain.

Materials and methods: Eleven chronic pain patients and eight healthy pain-free controls completed 12 weeks of supervised aerobic exercise intervention. Perceptual rating of standardized somatic pressure stimulation (2 kg) on the right anterior mid-thigh and brain responses during functional magnetic resonance imaging (fMRI) were assessed at pre- and postexercise rehabilitation.

Results: There was a significant difference in the perceptual rating of innocuous somatic pressure stimulation between the chronic pain and control groups (P=0.02) but no difference following exercise rehabilitation. Whole brain voxel-wise analysis with correction for multiple comparisons revealed trends for differences in fMRI responses between the chronic pain and control groups in the superior temporal gyrus (chronic pain > control, corrected P=0.30), thalamus, and caudate (control > chronic, corrected P=0.23). Repeated measures of the regions of interest (5 mm radius) for blood oxygen level-dependent signal response revealed trend differences for superior temporal gyrus (P=0.06), thalamus (P=0.04), and caudate (P=0.21). Group-by-time interactions revealed trend differences in the caudate (P=0.10) and superior temporal gyrus (P=0.29).

Conclusion: Augmented perceptual and brain responses to innocuous somatic pressure stimulation were shown in the chronic pain group compared to the control group; however, 12-weeks of exercise rehabilitation did not significantly attenuate these responses.

Effects of resistance or aerobic exercise training on interleukin-6, C-reactive protein, and body composition

PURPOSE: To determine the effects of 10 wk of resistance or aerobic exercise training on interleukin-6 (IL-6) and C-reactive protein (CRP). Further, to determine pretraining and posttraining associations between alterations of IL-6 and CRP and alterations of total body fat mass (TB-FM), intra-abdominal fat mass (IA-FM), and total body lean mass (TB-LM). METHODS: A sample of 102 sedentary subjects were assigned to a resistance group (n = 35), an aerobic group (n = 41), or a control group (n = 26). Before and after intervention, subjects were involved in dual-energy x-ray absorptiometry, muscular strength and aerobic fitness, measurements and further provided a resting fasted venous blood sample for measures of IL-6, CRP, cholesterol profile, triglycerides, glucose, insulin, and glycosylated hemoglobin. The resistance and the aerobic groups completed a respective 10-wk supervised and periodized training program, whereas the control group maintained sedentary lifestyle and dietary patterns. RESULTS: Both exercise training programs did not reduce IL-6; however, the resistance and the aerobic groups reduced CRP by 32.8% (P < 0.05) and 16.1% (P = 0.06), respectively. At baseline, CRP was positively correlated with IL-6 (r = 0.35), (TB-FM) (r = 0.36), and IA-FM (r = 0.31) and was inversely correlated with aerobic fitness measures (all r values > or = -0.24). Compared with the resistance and the control groups, the aerobic group exhibited significant (P < 0.05) improvements in all aerobic fitness measures and significant reductions in IA-FM (7.4%) and body mass (1.1%). Compared with the aerobic and the control groups, the resistance group significantly (P < 0.05) improved TB-FM (3.7%) and upper (46.3%) and lower (56.6%) body strength. CONCLUSION: Despite no alteration in baseline IL-6 and significantly smaller reductions in measures of adipose tissue as compared with the aerobic training group, only resistance exercise training resulted in significant attenuation of CRP concentration.

Perceptual and cerebro-spinal responses to graded innocuous and noxious stimuli following aerobic exercise

The aim of this study was to evaluate the effect of aerobic exercise on perceptual and cerebro-spinal responses to graded electrocutaneous stimuli. The design comprised 2 x 30 min of cycling exercise at 30% and 70% of peak oxygen consumption (VO2 peak) on separate occasions in a counter-balanced order in 10 healthy participants. Assessment of nociceptive withdrawal reflex threshold (NWR-T), pain threshold (PT), and somatosensory evoked potentials (SEPs) to graded electrocutaneous stimuli were performed before and after exercise. Perceptual magnitude ratings and SEPs were compared at 30%PT, 60%PT, 100%PT before (Pre), 5 min after (Post1), and 15 min after (Post2) aerobic exercise. There was no difference in the NWR-T and the PT following exercise at 30% and 70% of VO2 peak. ANOVA for the perceptual response within pooled electrocutaneous stimuli show a significant main effect for time (F2,18=5.41, P=0.01) but no difference for exercise intensity (F1,9=0.02, P=0.88). Within-subject contrasts reveal trend differences between 30%PT and 100%PT for Pre-Post1 (P=0.09) and Pre-Post2 (P=0.02). ANOVA for the SEPs peak-to-peak signal amplitude (N1-P1) show significant main effect for time (F2,18=4.04, P=0.04) but no difference for exercise intensity (F1,9=1.83, P=0.21). Pairwise comparisons for time reveal differences between Pre-Post1 (P=0.06) and Pre-Post2 (P=0.01). There was a significant interaction for SEPs N1-P1 between exercise intensity and stimulus intensity (F2,18=3.56, P=0.05). These results indicate that aerobic exercise did not increase the electrocutaneous threshold for pain and the NWR-T. Aerobic exercise attenuated perceptual responses to innocuous stimuli and SEPs N1-P1 response to noxious stimuli.

Haemodynamics of aerobic and resistance blood flow restriction exercise in young and older adults

PURPOSE: Light-load blood flow restriction exercise (BFRE) may provide a novel training method to limit the effects of age-related muscle atrophy in older adults. Therefore, the purpose of this study was to compare the haemodynamic response to resistance and aerobic BFRE between young adults (YA; n = 11; 22 ± 1 years) and older adults (OA; n = 13; 69 ± 1 years). METHOD: On two occasions, participants completed BFRE or control exercise (CON). One occasion was leg press (LP; 20 % 1-RM) and the other was treadmill walking (TM; 4 km h(-1)). Haemodynamic responses (HR, [Formula: see text], SV and BP) were recorded during baseline and exercise. RESULT: At baseline, YA and OA were different for some haemodynamic parameters (e.g. BP, SV). The relative responses to BFRE were similar between YA and OA. Blood pressures increased more with BFRE, and also for LP over TM. [Formula: see text] increased similarly for BFRE and CON (in both LP and TM), but with elevated HR and reduced SV (TM only). CONCLUSION: While BFR conferred slightly greater haemodynamic stress than CON, this was lower for walking than leg-press exercise. Given similar response magnitudes between YA and OA, these data support aerobic exercise being a more appropriate BFRE for prescription in older adults that may contribute to limiting the effects of age-related muscle atrophy.

Energy system interaction and relative contribution during maximal exercise

There are 3 distinct yet closely integrated processes that operate together to satisfy the energy requirements of muscle. The anaerobic energy system is divided into alactic and lactic components, referring to the processes  involved in the splitting of the stored phosphagens, ATP and  phosphocreatine (PCr), and the nonaerobic breakdown of carbohydrate to lactic acid through glycolysis. The aerobic energy system refers to the combustion of carbohydrates and fats in the presence of oxygen. The anaerobic pathways are capable of regenerating ATP at high rates yet are limited by the amount of energy that can be released in a single bout of intense exercise. In contrast, the aerobic system has an enormous capacity yet is somewhat hampered in its ability to delivery energy quickly. The focus of this review is on the interaction and relative contribution of the energy systems during single bouts of maximal exercise. A particular emphasis has been placed on the role of the aerobic energy system during high intensity exercise.

Attempts to depict the interaction and relative contribution of the energy systems during maximal exercise first appeared in the 1960s and 1970s. While insightful at the time, these representations were based on calculations of anaerobic energy release that now appear questionable. Given repeated reproduction over the years, these early attempts have lead to 2 common misconceptions in the exercise science and coaching professions. First, that the energy systems respond to the demands of intense exercise in an almost sequential manner, and secondly, that the aerobic system responds slowly to these energy demands, thereby playing little role in determining performance over short durations. More recent research suggests that energy is derived from each of the energy-producing pathways during almost all exercise activities. The duration of maximal exercise at which equal contributions are derived from the anaerobic and aerobic energy systems appears to occur between 1 to 2 minutes and most probably around 75 seconds, a time that is considerably earlier than has traditionally been suggested.

The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle

AS160 is an Akt substrate of 160 kDa implicated in the regulation of both insulin- and contraction-mediated GLUT4 translocation and glucose uptake. The effects of aerobic exercise and subsequent insulin stimulation on AS160 phosphorylation and the binding capacity of 14-3-3, a novel protein involved in the dissociation of AS160 from GLUT4 vesicles, in human skeletal muscle are unknown. Hyperinsulinemic-euglycemic clamps were performed on seven men at rest and immediately and 3 h after a single bout of cycling exercise. Skeletal muscle biopsies were taken before and after the clamps. The insulin sensitivity index calculated during the final 30 min of the clamp was 8.0 ± 0.8, 9.1 ± 0.5, and 9.2 ± 0.8 for the rest, postexercise, and 3-h postexercise trials, respectively. AS160 phosphorylation increased immediately after exercise and remained elevated 3 h after exercise. In contrast, the 14-3-3 binding capacity of AS160 and phosphorylation of Akt and AMP-activated protein kinase were only increased immediately after exercise. Insulin increased AS160 phosphorylation and 14-3-3 binding capacity and insulin receptor substrate-1 and Akt phosphorylation, but the response to insulin was not enhanced by prior exercise. In conclusion, the 14-3-3 binding capacity of AS160 is increased immediately after acute exercise in human skeletal muscle, but this is not maintained 3 h after exercise completion despite sustained AS160 phosphorylation. Insulin increases AS160 phosphorylation and 14-3-3 binding capacity, but prior exercise does not appear to enhance the response to insulin.

Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle

A single bout of aerobic exercise can enhance insulin action, but whether a similar effect occurs after resistance exercise is unknown. Hyperinsulinemic-euglycemic clamps were performed on eight male subjects at rest and after a single bout and three repeated bouts of resistance exercise over 7 days. Skeletal muscle biopsies were taken before and after the clamp and immediately after a single exercise bout. Whole-body insulin action measured by glucose infusion rate decreased (P < 0.05) after a single exercise bout, whereas in response to repeated bouts of resistance exercise, the glucose infusion rate was similar to the rest trial. In skeletal muscle, Akt substrate of 160 kDa (AS160) phosphorylation, an Akt substrate implicated in the regulation of GLUT4 translocation, and its interaction with 14-3-3 was decreased (P < 0.05) only after a single exercise bout. Insulin increased (P < 0.05) phosphorylation of AS160 and its interaction with 14-3-3, but the insulin response was not influenced by resistance exercise. Phosphorylation of insulin receptor substrate-1 and Akt were similar to changes in AS160 phosphorylation after exercise and/or insulin. In conclusion, a single bout of resistance exercise impairs whole-body insulin action. Regulation of AS160 and interaction with 14-3-3 in skeletal muscle are influenced by resistance exercise and insulin but do not fully explain the effect of resistance exercise on whole-body insulin action.

Mitofusions1/2 and ERRα expression are increased in human skeletal muscle after physical exercise.

Mitochondrial impairment is hypothesized to contribute to the pathogenesis of insulin resistance. Mitofusin (Mfn) proteins regulate the biogenesis and maintenance of the mitochondrial network, and when inactivated, cause a failure in the mitochondrial architecture and decreases in oxidative capacity and glucose oxidation. Exercise increases muscle mitochondrial content, size, oxidative capacity and aerobic glucose oxidation. To address if Mfn proteins are implicated in these exercise-induced responses, we measured Mfn1 and Mfn2 mRNA levels, pre-, post-, 2 and 24 h post-exercise. Additionally, we measured the expression levels of transcriptional regulators that control mitochondrial biogenesis and functions, including PGC-1α, NRF-1, NRF-2 and the recently implicated ERRα. We show that Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post-exercise, while PGC-1α and ERRα mRNA increased 2 h post-exercise. Finally, using in vitro cellular assays, we demonstrate that Mfn2 gene expression is driven by a PGC-1α programme dependent on ERRα. The PGC-1α/ERRα-mediated induction of Mfn2 suggests a role of these two factors in mitochondrial fusion. Our results provide evidence that PGC-1α not only mediates the increased expression of oxidative phosphorylation genes but also mediates alterations in mitochondrial architecture in response to aerobic exercise in humans.

Impaired K+ regulation contributes to exercise limitation in end-stage renal failure

Background

Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance.

Methods

Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (VdotO2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK).

Results

The VdotO2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 plusminus 0.38 vs. 6.23 plusminus 0.14 mmol dot L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 plusminus 0.05 vs. 0.23 plusminus 0.03 mmol dot L-1dotmin-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 plusminus 13.5 vs. 24.7 plusminus 3.3 nmol dot L-1dot J-1, P < 0.001). A strong inverse relationship was found between VdotO2 peak and the DeltaPKdot work-1 ratio (r = -0.80, N = 17, P < 0.001).

Conclusions

Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.

The effect of acute exercise on undercarboxylated osteocalcin in obese men

Summary : The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC.

Introduction : Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese individuals and individuals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC.

Methods : Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m⁻²) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO2peak) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood samples were taken at baseline and up to 2 h post-exercise.

Results : At baseline, unOC was negatively correlated with glucose levels (r = −0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = −0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L⁻¹, p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L⁻¹, p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = −0.46, p = 0.013 and r = −0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = −0.51, p = 0.038).

Conclusions : This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.r exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC.

Improvements in insulin resistance with exercise training: a lipocentric approach

Traditional views on the metabolic derangements underlying insulin resistance and Type 2 diabetes have been largely “glucocentric” in nature, focusing on the hyperglycemic and/or hyperinsulinemic states that result from impaired glucose tolerance. But in addition to glucose intolerance, there is a coordinated breakdown in lipid dynamics in individuals with insulin resistance, manifested by elevated levels of circulating free fatty acids, diminished rates of lipid oxidation, and excess lipid accumulation in skeletal muscle and/or liver. This review examines the premise that an oversupply and/or accumulation of lipid directly inhibits insulin action on glucose metabolism via changes at the level of substrate competition, enzyme regulation, intracellular signaling, and/or gene transcription. If a breakdown in lipid dynamics is causal in the development of insulin resistance (rather than a coincidental feature resulting from it), it should be possible to demonstrate that interventions that improve lipid homeostasis cause reciprocal changes in insulin sensitivity. Accordingly, the efficacy of aerobic endurance training in human subjects in mediating the association between deranged lipid metabolism and insulin resistance will be examined. It will be demonstrated that aerobic exercise training is a potent and effective primary intervention strategy in the prevention and treatment of individuals with insulin resistance.