Sean Carroll

What is the Relationship Between Exercise and Metabolic Abnormalities? A Review of the Metabolic Syndrome

Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the epidemic of type 2 diabetes mellitus and to reduce the increased risk of cardiovascular disease and all-cause mortality. Insulin resistance/hyperinsulinaemia are consistently linked with a clustering of multiple clinical and subclinical metabolic risk factors. It is now widely recognised that obesity (especially abdominal fat accumulation), hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that, concurrently, constitute the distinctive insulin resistance or metabolic syndrome. Cross-sectional and prospective data provide an emerging picture of associations of both physical activity habits and cardiorespiratory fitness with the metabolic syndrome. The metabolic syndrome, is a disorder that requires aggressive multi-factorial intervention. Recent treatment guidelines have emphasised the clinical utility of diagnosis and an important treatment role for ‘therapeutic lifestyle change’, incorporating moderate physical activity. Several previous narrative reviews have considered exercise training as an effective treatment for insulin resistance and other components of the syndrome. However, the evidence cited has been less consistent for exercise training effects on several metabolic syndrome variables, unless combined with appropriate dietary modifications to achieve weight loss.Recently published randomised controlled trial data concerning the effects of exercise training on separate metabolic syndrome traits are evaluated within this review. Novel systematic review and meta-analysis evidence is presented indicating that supervised, long-term, moderate to moderately vigorous intensity exercise training, in the absence of therapeutic weight loss, improves the dyslipidaemic profile by raising high density lipoprotein-cholesterol and lowering triglycerides in overweight and obese adults with characteristics of the metabolic syndrome. Lifestyle interventions, including exercise and dietary-induced weight loss may improve insulin resistance and glucose tolerance in obesity states and are highly effective in preventing or delaying the onset of type 2 diabetes in individuals with impaired glucose regulation. Randomised controlled trial evidence also indicates that exercise training decreases blood pressure in overweight/obese individuals with high normal blood pressure and hypertension. These evidence-based findings continue to support recommendations that supervised or partially supervised exercise training is an important initial adjunctive step in the treatment of individuals with the metabolic syndrome. Exercise training should be considered an essential part of ‘therapeutic lifestyle change’ and may concurrently improve insulin resistance and the entire cluster of metabolic risk factors.

Meta-analysis of walking for preservation of bone mineral density in postmenopausal women

Whilst exercise is recommended for optimum bone health in adult women, there are few systematic reviews of the efficacy of walking as singular exercise therapy for postmenopausal bone loss. The aim of this study was to assess the effects of prescribed walking programmes on bone mineral density (BMD) at the hip and spine in postmenopausal women and to determine if effects are modified by variations in protocol design. We undertook a systematic review and meta-analysis of randomised (RCTs) and non-randomised controlled trials. Electronic bibliographic databases, key journals and reference lists of reviews and articles were searched to identify studies for inclusion. Randomised and non-randomised controlled trials assessing the effects of walking on lumbar spine, femoral neck and total hip BMD, measured by radiographic techniques, among sedentary postmenopausal women were eligible for inclusion. Two independent reviewers assessed studies for eligibility. Reported absolute BMD outcomes were combined in the analysis. Weighted mean differences (WMD) were calculated using a fixed and random-effects models. Heterogeneity among trials was examined using the Q statistic and I2 methods. Potential publication bias was assessed through funnel plot inspection. Assessment of trial quality was also performed using the widely used instrument devised by Jadad et al. [Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Cont Clin Trials 1996; 17:1-12]. Eight trials were eligible for inclusion. Treatment duration ranged from 6 to 24 months. All eight trials reported BMD data at the lumbar spine following walking interventions among postmenopausal women. Meta-analysis showed no significant change in BMD at this site [WMD (fixed-effect) 0.007 g/cm2 95% CI (-0.001 to 0.016); P=0.09)]. BMD data at the femoral neck were available from five trials among postmenopausal women. Results were inconsistent (I2=51.4%) in showing a positive effect of walking on BMD at this site [WMD (random-effects) 0.014 g/cm2 95% CI (0.000 to 0.028); P=0.05). Insufficient data were available for meta-analysis of the total hip site. Funnel plots showed some asymmetry for negative lumbar spine BMD outcomes. Trial quality scores ranged from 0 to 3 from the Jadad scale of 0 to 5. We conclude that regular walking has no significant effect on preservation of BMD at the spine in postmenopausal women, whilst significant positive effects at femoral neck are evident. However, diverse methodological and reporting discrepancies are apparent in the published trials on which these conclusions are based. Other forms of exercise that provide greater targeted skeletal loading may be required to preserve bone mineral density in this population.

Effects of different impact exercise modalities on bone mineral density in premenopausal women : a meta-analysis

Our objective was to assess the effects of differing modes of impact exercise on bone density at the hip and spine in premenopausal women through systematic review and meta-analysis. Electronic databases, key journals and reference lists were searched for controlled trials investigating the effects of impact exercise interventions on lumbar spine (LS), femoral neck (FN) and total hip (TH) bone mineral density (BMD) in premenopausal women. Exercise protocols were categorised according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials was assessed. Fixed and random effects models were applied. Inspection of funnel plot symmetry was performed. Trial quality assessment was also undertaken. Combined protocols integrating odd- or high-impact exercise with high-magnitude loading (resistance exercises), were effective in increasing BMD at both LS and FN [WMD (fixed effect) 0.009xa0gxa0cm−2 95% CI (0.002–0.015) and 0.007xa0gxa0cm−2 95% CI (0.001–0.013); Pxa0=xa00.011 and 0.017, respectively]. High-impact only protocols were effective on femoral neck BMD [WMD (fixed effect) 0.024xa0gxa0cm−2 95% CI (0.002–0.027); Pxa0<xa00.00001]. Funnel plots showed some asymmetry for positive BMD outcomes. Insufficient numbers of protocols assessing TH BMD were available for assessment. Exercise programmes that combine odd- or high-impact activity with high-magnitude resistance training appear effective in augmenting BMD in premenopausal women at the hip and spine. High-impact-alone protocols are effective only on hip BMD in this group. However, diverse methodological and reporting discrepancies are evident in published trials.

The effects of a children's summer camp programme on weight loss, with a 10 month follow-up.

OBJECTIVE: To assess the long-term effects of a multidisciplinary approach involving structured fun-type skill learning physical activities in the treatment of obese and overweight children.DESIGN: A longitudinal investigation incorporating repeated measurements before and after the 8 week intervention and after the 44 week follow-up period.METHODS: The camp programme (Massachusetts, USA) utilised structured fun-based skill learning physical activities, moderate dietary restriction and behaviour modification. The primary aims of the intervention were to reduce body mass and promote the maintenance of the reduction in body mass using an alternative to standard exercise prescription.SUBJECTS: One-hundred and ninety-four children (64 boys and 130 girls, aged 12.6±2.5u2005y) enrolled at a summer weight loss camp, of which 102 children (38 boys and 64 girls aged 13.6±2.4u2005y) returned 1u2005y later.MEASUREMENTS: On commencement of the programme all children were assessed for body mass and stature. At follow-up, data was available on 102 subjects for body mass and stature.RESULTS: Over the 8 week intervention significant reductions (P=0.00) in body mass were obtained. During the 44 week follow-up significant increases (P=0.00) were noted in body mass, body mass index (BMI) and stature, but as expected there were large variations in the responses. One year after the initial measures had been taken mean body mass and BMI were lower than at the start of the intervention, BMI significantly so (week 0, 32.9±7.4u2005kg/m2; week 8 29.1±6.5u2005kg/m2; week 52, 30.05±7.04u2005kg/m2); (P=0.00). Stature increased significantly (week 0, 1.58±0.12u2005m; week 52, 1.64±0.11u2005m) (P=0.00) during this period, demonstrating a reduction in mean body mass over a 1u2005y period whilst subjects continued to increase in stature. When changes in BMI are analysed with the use of standard scores, there is a non-significant increase (P=0.07) in BMI during the follow-up phase and 89% of children had a lower BMI than at week 0.CONCLUSIONS: These findings suggest that the use of a structured fun-based skill learning programme may provide an alternative method of exercise prescription to help children prolong the effects of the 8 week intervention. Further investigations will help identify the key factors that are necessary for long-term lifestyle modification.

Metabolic clustering, physical activity and fitness in nonsmoking, middle-aged men

PURPOSEnThe relationship of both physical activity and predicted maximum oxygen consumption (VO2max) with the clustering of metabolic risk factors associated with the metabolic syndrome (MS) was examined within 711 employed middle-aged (46.9 +/- 7.8 yr) men.nnnMETHODSnMetabolic markers included fasting glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure, and BMI, defined by highest risk quintiles or clinically relevant risk thresholds.nnnRESULTSnThe prevalence and age-adjusted odds ratios of all MS clusters were inversely graded across both higher physical activity index (PAI) and cardiorespiratory fitness (CRF) categories. The age-adjusted odds ratio for the clustering of clinically relevant metabolic markers was 0.60 (95% CI 0.22-1.22) for subjects in the occasional/light PAI, 0.32 (95% CI 0.12-0.82) for the moderate/moderately vigorous PAI, and 0.13 (95% CI 0.02-1.02) for the vigorous PAI when compared with subjects in the sedentary PAI (P < 0.05 for trend). The corresponding age-adjusted odds ratio was 0.28 (95% CI 0.14-0.57) for subjects in the moderate fitness category and 0.12 (95% CI 0.05-0.32) for the highest fitness category compared with those in the lowest fitness category (P < 0.001 for trend). Higher levels of physical activity or CRF were also associated with significantly lower age-adjusted odds ratios for the MS after exclusion of obesity in the MS definition.nnnCONCLUSIONnOverall, these cross-sectional results suggest that higher physical activity and predicted VO2max levels are associated with a decreased clustering of risk factors associated with the MS in middle-aged men of higher social class.

Emergence of the verification phase procedure for confirming ‘true’V̇O2max

Traditional V̇O2max criteria are typically based on attainment of a V̇O2 plateau, and threshold values for the respiratory exchange ratio, heart rate and blood lactate concentration. Despite long‐standing criticisms directed at these criteria, their use remains widespread. This article discusses an alternative procedure, termed the verification phase, for confirming the attainment of true V̇O2max. Following a continuous incremental exercise test to the limit of tolerance and appropriate recovery period, the verification phase is performed and is characterized by a supramaximal square wave exercise bout. Consistent peak V̇O2 values in the incremental and verification phases, confirms that a true V̇O2max has been attained. Six recent studies investigated the utility of the verification phase for evaluating true V̇O2max. These studies consistently found small insignificant mean differences between the maximal V̇O2 attained in the incremental and verification phases. However, this group mean approach does not identify individual subjects who may not have attained a true V̇O2max. Notably, only one of the six studies reported a criterion threshold to verify the V̇O2max of individual subjects. Further research is required to investigate the utility of different verification phase procedures and to establish a suitable verification criterion threshold for confirming true V̇O2max.

Plasma viscosity, fibrinogen and the metabolic syndrome : effect of obesity and cardiorespiratory fitness

&NA; The association between both plasma viscosity and fibrinogen concentration with clustering of metabolic risk markers was examined within a cross‐sectional study of employed middle‐aged men. Analyses were performed on a subsample of 629 non‐smokers (46.7 ± 7.8 years) without diabetes. The effect of obesity and cardiorespiratory fitness on these haemorheological parameters and their association with the metabolic syndrome was also investigated. The cohort was grouped by the number of metabolic markers present. Metabolic markers included high‐density lipoprotein‐cholesterol (< 1.13 mmol/l), triglycerides (≥ 1.805 mmol/l), glucose (≥ 5.5 mmol/l) and diastolic blood pressure (≥ 90 mmHg). The age‐adjusted odds ratio for hyperviscosity (≥ 1.67 mPa/s) was 2.08 [95% confidence interval (CI), 1.06‐4.05; P = 0.031] for the subjects with the metabolic syndrome (three or more metabolic markers) when compared with those with no metabolic abnormalities. The comparable age‐adjusted odds ratio for hyperfibrinogenaemia (≥ 3.47 g/l) was non‐significantly higher at 1.69 (95% CI, 0.87‐3.27; P = 0.119). The mean age‐adjusted plasma viscosity level and the prevalence of hyperviscosity increased significantly from 1.629 to 1.692 mPa/s (P = 0.0005) and from 21.0 to 36.0% with accumulating metabolic markers (P = 0.006). Plasma viscosity and fibrinogen concentration both increased with higher quartiles of skinfolds (P = 0.003 and P = 0.01, respectively) following adjustment for age, lipids and leucocyte count. Plasma viscosity was also significantly lower with higher levels of predicted maximum oxygen consumption (&OV0312;o2max) (P = 0.0005). The odds ratio for hyperviscosity in subjects with the metabolic syndrome as compared with those with no metabolic markers was attenuated following adjustment for age, sum of skinfolds and predicted maximum oxygen consumption (&OV0312;o2max) (1.44; 95% CI, 0.72‐2.90; P = 0.307). These cross‐sectional results suggest that plasma viscosity is associated with increased clustering of metabolic markers in middle‐aged men of high socio‐economic status. Obesity and poor cardiorespiratory fitness may be important in the development of haemorheological abnormalities associated with the metabolic syndrome.

Estimating changes in hydration status from changes in body mass: Considerations regarding metabolic water and glycogen storage

Abstract The potential for imprecision in the estimation of hydration status from changes in body mass has been outlined previously but the equations derived from these derivations appear inconsistent. Reconciliation of body mass loss in terms of sweat loss and effective body water loss is possible from specific equation sets provided that gains and losses of both body mass and water used in the derivation of sweat loss and to derive effective body water loss are in inclusive equation sets. This is obligatory so that mass and water changes as quantifiable determinants are consistent with both internal processes and external gains and losses. Thus, body mass loss, substrate oxidation, metabolic water, and all the terms used in simultaneous equation sets have to be reconciled not only as identical variables but mathematically balance exactly. The revised equation for effective body water loss given here is different from that originally proposed. Metabolic water is part of body mass loss corrected for substrate oxidation, fluid ingestion, and respiratory water to derive sweat loss and it may not be justified to also include water associated with glycogen as releasable bound water. Accordingly, our calculated effective body water loss is substantially a greater loss than originally supposed but clearly still less than the simple balance between mass loss and fluid ingested.

Impact of a Short-Term, Moderate Intensity, Lower Volume Circuit Resistance Training Programme on Metabolic Risk Factors in Overweight/Obese Type 2 Diabetics

The purpose of this study was to evaluate the effects of an 8-week, low frequency, hospital-based resistance training programme on metabolic risk factors in type 2 diabetic patients. Participants were self-selected into either an 8-week resistance training programme or a control group. Anthropometric indices, fasting glucose, HbA1c, total cholesterol, HDL and LDL lipoproteins, triglycerides, fasting insulin, and insulin sensitivity were assessed at baseline and 8 weeks later. Six participants were recruited (age 53 ± 9 years; BMI 32 ± 3 kg·m−2), and a further six participants acted as controls (age 55 ± 9 years; BMI 31 ± 3 kg·m−2). After training, waist circumference and waist-to-hip ratio were significantly reduced, with no associated changes in the control group. Metabolic risk factors remained unchanged following training (P > 0.05). We concluded that an 8-week, low frequency, resistance training programme reduced abdominal fat content but had little impact on metabolic risk factor modification in type 2 diabetics.

Differential Improvements in Lipid Profiles and Framingham Recurrent Risk Score in Patients With and Without Diabetes Mellitus Undergoing Long-Term Cardiac Rehabilitation

UNLABELLEDnnnnOBJECTIVEnTo determine whether lipid profiles and recurrent coronary heart disease (CHD) risk could be modified in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation (CR).nnnDESIGNnRetrospective analysis of patient case records.nnnSETTINGnCommunity-based phase 4 CR program.nnnPARTICIPANTSnPatients without diabetes (n=154; 89% men; mean ± SD age, 59.6 ± 8.5y; body mass index [BMI], 27.0 ± 3.5 kg/m²) and patients with diabetes (n=20; 81% men; mean age, 63.0 ± 8.7y; BMI, 28.7 ± 3.3 kg/m²) who completed 15 months of CR.nnnINTERVENTIONSnExercise testing and training, risk profiling, and risk-factor education.nnnMAIN OUTCOME MEASURESnCardiometabolic risk factors and 2- to 4-year Framingham recurrent CHD risk scores were assessed.nnnRESULTSnAt follow up, a significant main effect for time was evident for decreased body mass and waist circumference and improved low-density lipoprotein cholesterol (LDL-C) level and submaximal cardiorespiratory fitness (all P<.05), showing the benefits of CR in both groups. However, a significant group-by-time interaction effect was evident for high-density lipoprotein cholesterol (HDL-C) level and total cholesterol (TC)/HDL-C ratio (both P<.05). TC/HDL-C ratio improved (5.0 ± 1.5 to 4.4 ± 1.3) in patients without diabetes, but showed no improvement in patients with diabetes (4.8 ± 1.6 v 4.9 ± 1.6).nnnCONCLUSIONSnWe showed that numerous anthropometric, submaximal fitness, and cardiometabolic risk variables (especially LDL-C level) improved significantly after long-term CR. However, some aspects of cardiometabolic risk (measures incorporating TC and HDL-C) improved significantly in only the nondiabetic group.