Exercise for patients with chronic kidney disease: from cells to systems to function.

Chronic kidney disease (CKD) is among the leading causes of death and disability, affecting an estimated 800 million adults globally. The underlying pathophysiology of CKD is complex creating challenges to its management. Primary risk factors for the development and progression of CKD include diabetes mellitus, hypertension, age, obesity, diet, inflammation, and physical inactivity. The high prevalence of diabetes and hypertension in patients with CKD increases the risk for secondary consequences such as cardiovascular disease and peripheral neuropathy. Moreover, the increased prevalence of obesity and chronic levels of systemic inflammation in CKD have downstream effects on critical cellular functions regulating homeostasis. The combination of these factors results in the deterioration of health and functional capacity in those living with CKD. Exercise offers protective benefits for the maintenance of health and function with age, even in the presence of CKD. Despite accumulating data supporting the implementation of exercise for the promotion of health and function in patients with CKD, a thorough description of the responses and adaptations to exercise at the cellular, system, and whole body levels is currently lacking. Therefore, the purpose of this review is to provide an up-to-date comprehensive review of the effects of exercise training on vascular endothelial progenitor cells at the cellular level; cardiovascular, musculoskeletal, and neural factors at the system level; and physical function, frailty, and fatigability at the whole body level in patients with CKD.

An exercise stress test for contrast-enhanced duplex ultrasound assessment of lower limb muscle perfusion in patients with peripheral arterial disease.

OBJECTIVE: The aim of the present study was to develop a standardized contrast-enhanced duplex ultrasound (CE-DUS) protocol to assess lower-extremity muscle perfusion before and after exercise and determine relationships of perfusion with clinical and functional measures. METHODS: CE-DUS (EPIQ 5G, Philips) was used before and immediately after a 10-minute, standardized bout of treadmill walking to compare microvascular perfusion of the gastrocnemius muscle in older (55-82 years) patients with peripheral arterial disease (PAD) (n = 15, mean ankle-brachial index, 0.78 ± 0.04) and controls (n = 13). Microvascular blood volume (MBV) and microvascular flow velocity (MFV) were measured at rest and immediately following treadmill exercise, and the Modified Physical Performance Test (MPPT) was used to assess mobility function. RESULTS: In the resting state (pre-exercise), MBV in patients with PAD was not significantly different than normal controls (5.17 ± 0.71 vs 6.20 ± 0.83 arbitrary units (AU) respectively; P = .36); however, after exercise, MBV was ∼40% lower in patients with PAD compared with normal controls (5.85 ± 1.13 vs 9.53 ± 1.31 AU, respectively; P = .04). Conversely, MFV was ∼60% higher in patients with PAD compared with normal controls after exercise (0.180 ± 0.016 vs 0.113 ± 0.018 AU, respectively; P = .01). There was a significant between-group difference in the exercise-induced changes in both MBV and MFV (P ≤ .05). Both basal and exercise MBV directly correlated with MPPT score in the patients with PAD (r = 0.56-0.62; P < .05). CONCLUSIONS: This standardized protocol for exercise stress testing of the lower extremities quantifies calf muscle perfusion and elicits perfusion deficits in patients with PAD. This technique objectively quantifies microvascular perfusion deficits that are related to reduced mobility function and could be used to assess therapeutic efficacy in patients with PAD.

Gluteal muscle fatty infiltration, fall risk, and mobility limitation in older women with urinary incontinence: a pilot study.

OBJECTIVE: Gluteal muscle quality influences risk of falling and mobility limitation. We sought (1) to compare gluteal muscle fatty infiltration (FI) between groups of older women with urinary incontinence (UI) at risk for falling (at-risk group) and not at risk for falling (not-at-risk group), and (2) to determine correlation of gluteal FI with Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) performance. MATERIALS AND METHODS: Prospective pilot study of gluteal FI on pelvis MRI for 19 women with UI, aged ≥ 70 years. A musculoskeletal radiologist selected axial T1-weighted MR images; then, two blinded medical student research assistants analyzed gluteal FI by quantitative fuzzy C-means segmentation. TUG and SPPB tests were performed. TUG ≥ 12 s defined participants as at risk for falling. Descriptive, correlation, and reliability analyses were performed. RESULTS: Mean age, 76.3 ± 4.8 years; no difference for age or body mass index (BMI) between the at-risk (n = 5) versus not-at-risk (n = 14) groups. SPPB score (p = 0.013) was lower for the at-risk group (6.4 ± 3.1) than for the not-at-risk group (10.2 ± 1.9). Fuzzy C-means FI-%-estimate differed between the at-risk group and the not-at-risk group for bilateral gluteus medius/minimus (33.2% ± 15.6% versus 19.5% ± 4.1%, p = 0.037) and bilateral gluteus maximus (33.6% ± 15.6% versus 19.7% ± 6.9%, p = 0.047). Fuzzy C-means FI-%-estimate for bilateral gluteus maximus had significant (p < 0.050) moderate correlation with age (rho = - 0.64), BMI (rho = 0.65), and TUG performance (rho = 0.52). Fuzzy C-means FI-%-estimates showed excellent inter-observer and intra-observer reliability (intraclass correlation coefficient, ≥ 0.892). CONCLUSION: Older women with UI at risk for falling have greater levels of gluteal FI and mobility limitation as compared to those not at risk for falling.

Predictive Equations Overestimate Resting Metabolic Rate in Survivors of Chronic Stroke.

OBJECTIVE: To measure resting metabolic rate (RMR) in survivors of chronic (>3 months prior) stroke (mean ± SEM age, 61±7.5 years) and to compare to predicted RMR using predictive equations in adults without stroke. DESIGN: Cross-sectional study. SETTING: Hospital. PARTICIPANTS: Survivors of stroke (N=71). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: RMR was measured by indirect calorimetry. Participants underwent a total body dual-energy x-ray absorptiometry scan and treadmill test for peak oxygen consumption (V̇o2peak). RMR was calculated using 9 established equations. RESULTS: RMR measured (1552±319 kcal/d) was significantly lower than 9 predicted RMR values (all P<.001), with the best being McArdle-Katch (1652±233 kcal/d), Livingston (1677±230 kcal/d), and Mifflin (1707±242 kcal/d). The Institute of Medicine of the National Academies (2437±386 kcal/d) had the largest discrepancy with measured RMR. Predicted RMR determined with 8 of 9 equations was between 9% and 18% greater than measured RMR. Appendicular lean mass (r=0.64, P<.001), total lean mass (r=0.64, P<.001), and V̇o2peak (r=0.41, P<.001) were associated with measured RMR. CONCLUSIONS: RMR predictive equations established in adults without stroke are not appropriate for the population with stroke population, indicating the need to measure RMR until a more accurate predictive equation is developed. This could support modifications to nutritional intake guidelines in patients with conditions of muscle atrophy. If measurement of RMR is not feasible, the Katch-McArdle equation should be used to estimate RMR in a patient with stroke because on average it provides the lowest percentage overestimate compared with other equations.

Systematic Review of the Importance of Hip Muscle Strength, Activation, and Structure in Balance and Mobility Tasks.

OBJECTIVE: The aim of this systematic review was to identify the associations of the hip abductor muscle strength, structure, and neuromuscular activation on balance and mobility in younger, middle-aged, and older adults. DATA SOURCES: We followed PRISMA guidelines and performed searches in PubMed, Embase, CINAHL, and Physiotherapy Evidence Database. STUDY SELECTION: Study selection included: (1) studies with patients aged 18 years or older and (2) studies that measured hip abduction torque, surface electromyography, and/or muscle structure and compared these measures with balance or mobility outcomes. DATA EXTRACTION: The extracted data included the study population, setting, sample size, sex, and measurement evaluated. DATA SYNTHESIS: The present systematic review is composed of 59 research articles including a total of 2144 young, middle-aged, and older adults (1337 women). We found that hip abductor strength is critical for balance and mobility function, independent of age. Hip abductor neuromuscular activation is also important for balance and mobility, although it may differ across ages depending on the task. Finally, the amount of fat inside the muscle appears to be one of the important factors of muscle structure influencing balance. CONCLUSIONS: In conclusion, a change in all investigated variables (hip abduction torque, neuromuscular activation, and intramuscular fat) appears to have an effect during balance or mobility tasks across age ranges and may elicit better performance. Future studies are necessary to confirm the effect of these variables across age ranges and the effects of interventions.

Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke.

OBJECTIVE: To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health. DESIGN: Randomized controlled trial. SETTING: The general communities of Baltimore, Maryland, and Atlanta, Georgia. PARTICIPANTS: Two hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246). INTERVENTION: Participants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;). MAIN OUTCOME MEASURE(S): Peak oxygen uptake rate (V̇o2peak), 6-minute walking distance (6MWD), fasting plasma glucose, insulin, oxidative stress, and inflammatory biomarkers were assessed pre- and postintervention. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. RESULTS: Physical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V̇o2peak: -9% vs 24%, P<.01; 6MWD: 1% vs 15%, P=.05; insulin: -1% vs -31%, P=.05; HOMA-IR: -3% vs -29%, P=.06). Plasma concentrations of nitrotyrosine, protein carbonyls, and oxidized low-density lipoprotein (oxLDL) tended to decrease from pre-intervention concentrations in response to TM compared to ST (ST vs TM: nitrotyrosine: 2% vs -28%, P=.01; protein carbonyls: -4% vs -34%, P=.08; oxLDL: -3% vs -32%, P<.01). Changes in circulating concentrations of C-reactive protein, protein carbonyls, and oxLDL were negatively associated with changes in V̇o2peak and 6MWD (r's=-0.40 to -0.76) and positively associated with fasting plasma insulin and HOMA-IR (r's=0.52-0.81, Ps<.01). CONCLUSIONS: Six months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.

Depressive symptom heterogeneity among older adults after hip fracture.

OBJECTIVE: to evaluate patterns of depressive symptoms after hip fracture and examine their impact on functional recovery. METHODS: participants (n = 304) included older adults from the Baltimore Hip Studies 7th cohort who experienced a hip fracture. Depressive symptoms were measured at baseline or 2-, 6- or 12-month post-hip fracture using the 20-item Center for Epidemiologic Studies Depression scale. Gait speed was measured after hip fracture at 2-, 6- or 12-month follow-up. Latent class analysis was used to identify individuals with similar patterns of depressive symptoms after hip fracture. Item response probabilities characterised symptom profiles, and posterior probability estimates were used to assign participants to a baseline depressive symptom subtype. Weighted estimated equations compared post-fracture gait speed between baseline symptomatic and asymptomatic groups. RESULTS: four patterns of depressive symptoms were identified: asymptomatic (50.8%), somatic (28.6%), melancholic (11.4%) and anhedonic (9.2%). The somatic subtype was characterised by difficultly concentrating and reduced energy and movement, whereas anhedonic symptoms were associated with the inability to experience pleasure. Melancholic symptoms corresponded to anhedonia, decreased physical activity and other psychological and somatic complaints. Compared with the asymptomatic group, somatic symptoms were consistently associated with slower gait speed, -0.03 metres per second (m/s) and between-group differences for melancholic symptomology were as large as -0.05 m/s, but the associations were not statistically significant. CONCLUSION: findings demonstrate unique depressive symptom subtypes in older adults after hip fracture and provide confirmatory evidence of unique clinical phenotypes; however, their impact on functional recovery after hip fracture remains unclear.

Physical performance measures in older women with urinary incontinence: pelvic floor disorder or geriatric syndrome?

INTRODUCTION AND HYPOTHESIS: To evaluate physical performance measures of mobility and functional impairments and assess their association with urinary incontinence (UI) severity and impact on quality of life among older women with UI. METHODS: In a cross-sectional pilot study, 20 women aged ≥ 70 years with UI completed UI questionnaires (Global Impression of Severity, Incontinence Impact Questionnaire [IIQ-7]) and functional status evaluation. Functional status evaluation included the Modified Physical Performance Test (MPPT; range 0-36), Short Physical Performance Battery (SPPB; range 0-12), and other physical performance measures (e.g., Timed Up and Go [TUG]). MPPT and SPPB scores < 32 and < 10, respectively, indicated impaired mobility and function. Descriptive statistics and Spearman correlation coefficients evaluated study variables and associations between UI and physical performance measures. RESULTS: Women were 76.6 ± 4.7 years old with mean body mass index 33.5 ± 9.0 kg/m2. Mixed UI was the most prevalent (n = 17; 85%), and 14 (70%) participants rated their UI as moderate or severe. Low MPPT (< 32) and SPPB (< 10) scores were present in 65% (n = 13) and 35% (n = 7) of participants, respectively. Lower MPPT score (r = -0.46; P = 0.04) and worse TUG performance (r = 0.50; P = 0.03) were associated with greater UI impact on quality of life based on IIQ-7. SPPB did not correlate (P > 0.05) with UI measures. CONCLUSIONS: Mobility and functional impairments are common among older women with UI. Associations between MPPT score and TUG performance with UI impact on quality of life suggest these physical performance measures could be markers of mobility and functional impairments in future research on UI in older women.

Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization. METHODS: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m2 were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90. RESULTS: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = -  0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90. CONCLUSIONS: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.

Feasibility and effects of high-intensity interval training in older adults living with HIV.

Adults with HIV on therapy can live a normal lifespan but exhibit advanced ageing which includes reduced cardiorespiratory fitness. Our objective was to determine the feasibility and effects of high-intensity interval training (HIIT) combined with resistance training (RT) in older adults with HIV. We conducted a cross-over pilot study within a randomized exercise trial in sedentary adults with HIV ≥50 years of age. First, participants were randomized to 4 months of continuous high-intensity aerobic exercise (AEX) and RT 3x/week or standard of care control. Then, the control group completed 4 months of HIIT + RT (3x/week). Among the 32 individuals enrolled, 26 eligible participants were randomized. Most participants were African American (63%) and male (95%) with a mean (SD) age of 61.5 (6.7) years and VO2peak of 24.5 (4.9) ml/kg/min. Attendance and adherence to both exercise training interventions were high. The clinically significant increases in VO2peak (ml/kg/min) after HIIT (3.09 ±1.04, p=0.02) and AEX (2.09 ±0.72, p=0.01) represented improvements of 17.1% and 7.7%, respectively. Both groups had improvements in exercise endurance (time on the treadmill) and strength (all p< 0.01). This pilot study supports HIIT as an efficient means to deliver high-intensity AEX to improve cardiorespiratory fitness toward the goal of attenuating the accelerated ageing process in adults with HIV.

Association between disease progression and depression onset in persons with radiographic knee osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA. METHODS: Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale <16] at baseline were included. Disease severity was measured from baseline to the third annual follow-up visit using joint space width, 20-meter gait speed, and the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, each categorized into quintiles. Depression onset (CES-D ≥ 16) was assessed annually at four follow-up visits. Marginal structural models that account for time-dependent confounding and attrition evaluated the association between each time-varying disease severity measure and depression onset. RESULTS: Each disease severity measure exhibited a non-linear relationship concerning the probability of depression onset, with the higher quintiles generally being associated with a larger risk. The highest quintile (relative to the lowest) of joint space width and gait speed were both significantly associated with depression onset. By contrast, none of the higher pain quintiles compared with the lowest were significantly associated with the onset of depression. CONCLUSION: Faster disease progression as measured by either worsening structural severity or decreasing physical performance corresponds to an increased risk of depression among individuals with radiographic knee OA.

Insulin suppression of fatty acid skeletal muscle enzyme activity in postmenopausal women, and improvements in metabolic flexibility and lipoprotein lipase with aerobic exercise and weight loss.

BACKGROUND: Obesity and insulin resistance are characterized by metabolic inflexibility, a condition described as an inability to switch from fat oxidation during fasting to carbohydrate oxidation during hyperinsulinemia. The purpose of this study was to examine predictors of metabolic flexibility in 103 obese (37-59% fat), sedentary (VO2max: 19.4 ± 0.5 ml/kg/min), postmenopausal (45-76 years) women, and changes in metabolic flexibility with exercise and weight loss interventions. METHODS: Insulin sensitivity (M) and metabolic flexibility via an 80 mU/m2/min hyperinsulinemic-euglycemic clamp, VO2max, and body composition were measured. Metabolic flexibility was measured after 6-months aerobic training + weight loss (AEX + WL: n = 43) or weight loss (WL: n = 31). Basal and insulin-stimulated vastus lateralis skeletal muscle samples were available from a subset of these women (n = 45). RESULTS: Metabolic flexibility correlated inversely with glucose120 min of OGTT, fasting insulin, and the percent change (insulin-basal) in lipoprotein lipase (LPL) activity and positively with M, but not with VO2max, total body fat, visceral fat, or subcutaneous abdominal fat. Skeletal muscle acyl-CoA synthase and citrate synthase activities decreased during hyperinsulinemia. Metabolic flexibility increased after AEX + WL but not WL, and the percent change in metabolic flexibility was inversely related to the percent change in insulin's effect on LPL activity. CONCLUSION: Metabolic flexibility is related to insulin sensitivity and insulin's action on LPL. Furthermore, metabolic flexibility and insulin suppression of skeletal muscle LPL activity increase with AEX + WL in overweight and obese, sedentary older women.

Metabolomics of Aerobic Exercise in Chronic Stroke Survivors: A Pilot Study.

BACKGROUND: Understanding the metabolic response to exercise may aid in optimizing stroke management. Therefore, the purpose of this pilot study was to evaluate plasma metabolomic profiles in chronic stroke survivors following aerobic exercise training. METHODS: Participants (age: 62 ± 1 years, body mass index: 31 ± 1 kg/m2, mean ± standard error of the mean) were randomized to 6 months of treadmill exercise (N = 17) or whole-body stretching (N = 8) with preintervention and postintervention measurement of aerobic capacity (VO2peak). Linear models for microarray data expression analysis was performed to determine metabolic changes over time, and Mummichog was used for pathway enrichment analysis following analysis of plasma samples by high-performance liquid chromatography coupled to ultrahigh resolution mass spectrometry. RESULTS: VO2peak change was greater following exercise than stretching (18.9% versus -.2%; P < .01). Pathway enrichment analysis of differentially expressed metabolites results showed significant enrichment in 4 pathways following treadmill exercise, 3 of which (heparan-, chondroitin-, keratan-sulfate degradation) involved connective tissue metabolism and the fourth involve lipid signaling (linoleate metabolism). More pathways were altered in pre and post comparisons of stretching, including branched-chain amino acid, tryptophan, tyrosine, and urea cycle, which could indicate loss of lean body mass. CONCLUSIONS: These preliminary data show different metabolic changes due to treadmill training and stretching in chronic stroke survivors and suggest that in addition to improved aerobic capacity, weight-bearing activity, like walking, could protect against loss of lean body mass. Future studies are needed to examine the relationship between changes in metabolomic profiles to reductions in cardiometabolic risk after treadmill rehabilitation.

Type 2 diabetes and older age contribute to elevated plasma microparticle concentrations independent of chronic stroke.

NEW FINDINGS: What is the central question of this study? What is the effect of chronic stroke on circulating microparticle populations, accounting for potential effects of age and type 2 diabetes? What is the main finding and its importance? Elevated concentrations of CD31+ /CD42b- and CD62E+ microparticles appear to be driven by type 2 diabetes but not chronic stroke and are associated with fasting glucose and triglyceride levels. Older age results in elevations in CD62E+ and CD34+ microparticle concentrations. These microparticles have been proposed as potential targets for diagnosing, treating and identifying the clinical progression and complications of type 2 diabetes. ABSTRACT: The elevated circulating concentration of endothelial microparticles (MPs) may provide an index of the extent and nature of cellular damage in chronic stroke. The purpose of this study was to determine the circulating concentrations of CD31+ /CD42b- , CD62E+ and CD34+ MPs in chronic stroke subjects, focusing on the effects of chronic stroke by comparison with both older adults without a history of stroke but with type 2 diabetes mellitus (T2DM) and older and young healthy controls. Plasma from three groups of sedentary older (50-75 years) men and women (chronic stroke, T2DM or older healthy) as well as a group of younger (18-39 years) healthy controls was isolated from fasting blood, and CD31+ /CD42b- , CD62E+ and CD34+ MPs were quantified using flow cytometry (n = 17/group). Concentrations of CD31+ /CD42b- and CD62E+ MPs were higher in the T2DM group (P < 0.05), but not chronic stroke, compared to older and younger healthy adults. CD62E+ MP and CD34+ MP concentrations were elevated in the older compared to younger adults (P < 0.05 for both). Sub-analyses excluding chronic stroke subjects who were also diagnosed with diabetes [stroke (diabetes- )] revealed lower CD31+ /CD42b- (P < 0.05) and CD62E+ (P = 0.08) MPs in the stroke (diabetes- ) group compared to the T2DM group. CD31+ /CD42b- MP and CD62E+ MP concentrations were each associated with fasting glucose levels and CD31+ /CD42b- MPs also were associated with triglyceride levels. As MPs have been proposed as potential targets for diagnosing, treating and identifying the clinical progression of T2DM, our study provides further support for the use of CD31+ /CD42b- and CD62E+ MPs in the clinical progression of T2DM and associated vascular complications.

Sarcopenia in Peripheral Arterial Disease: Prevalence and Effect on Functional Status.

OBJECTIVES: (1) To determine the prevalence of sarcopenia in older men with peripheral arterial disease (PAD); (2) to compare a subgroup of the group with age-, race-, sex-, and body mass index (BMI)-matched non-PAD control counterparts, and (3) to compare the functional status of those with PAD with and without sarcopenia. DESIGN: Cohort study. SETTING: Medical center. PARTICIPANTS: Sedentary community-dwelling men (N=108; age, >50y) with a confirmed diagnosis of PAD (44% blacks; BMI, 27.8±0.4kg/m2; ankle-brachial index, .62±.01). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans were used to assess appendicular lean mass and determine the prevalence of sarcopenia by/height2. Treadmill tests were used to determine claudication onset time, peak walking time, and claudication recovery time. 6-Minute walk distance was also measured. RESULTS: Sarcopenia prevalence in our PAD cohort was 25%. The PAD subgroup (n=42) matched with control counterparts in terms of race, sex, age, and BMI had higher prevalence rates than did their non-PAD counterparts (23.8% vs 2.4%; P<.05). Individuals with sarcopenia (n=28) had a shorter 6-minute walk distance (326±18.8m vs 380±9.7m; P<.05) and higher claudication recovery time (592±98s vs 395±29s; P<.05) than did individuals with PAD but without sarcopenia (n=80). There was no difference in claudication onset time or peak walking time between the PAD groups. CONCLUSIONS: Men with PAD demonstrate a high prevalence of sarcopenia. Those with sarcopenia and PAD demonstrate decreased mobility function.

Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes.

BACKGROUND: Lipolysis regulates energy homeostasis through the hydrolysis of intracellular triglycerides and the release of fatty acids for use as energy substrates or lipid mediators in cellular processes. Genes encoding proteins that regulate energy homeostasis through lipolysis are thus likely to play an important role in determining susceptibility to metabolic disorders. METHODS: We sequenced 12 lipolytic-pathway genes in Old Order Amish participants whose fasting serum triglyceride levels were at the extremes of the distribution and identified a novel 19-bp frameshift deletion in exon 9 of LIPE, encoding hormone-sensitive lipase (HSL), a key enzyme for lipolysis. We genotyped the deletion in DNA from 2738 Amish participants and performed association analyses to determine the effects of the deletion on metabolic traits. We also obtained biopsy specimens of abdominal subcutaneous adipose tissue from 2 study participants who were homozygous for the deletion (DD genotype), 10 who were heterozygous (ID genotype), and 7 who were noncarriers (II genotype) for assessment of adipose histologic characteristics, lipolysis, enzyme activity, cytokine release, and messenger RNA (mRNA) and protein levels. RESULTS: Carriers of the mutation had dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. In adipose tissue from study participants with the DD genotype, the mutation resulted in the absence of HSL protein, small adipocytes, impaired lipolysis, insulin resistance, and inflammation. Transcription factors responsive to peroxisome-proliferator-activated receptor γ (PPAR-γ) and downstream target genes were down-regulated in adipose tissue from participants with the DD genotype, altering the regulation of pathways influencing adipogenesis, insulin sensitivity, and lipid metabolism. CONCLUSIONS: These findings indicate the physiological significance of HSL in adipocyte function and the regulation of systemic lipid and glucose homeostasis and underscore the severe metabolic consequences of impaired lipolysis. (Funded by the National Institutes of Health and others).

Role of Hip Abductor Muscle Composition and Torque in Protective Stepping for Lateral Balance Recovery in Older Adults.

OBJECTIVES: To examine differences in hip abductor strength and composition between older adults who primarily use medial step versus cross-step recovery strategies to lateral balance perturbations. DESIGN: Cross-sectional. SETTING: University research laboratory. PARTICIPANTS: Community-dwelling older adults (N=40) divided into medial steppers (n=14) and cross-steppers (n=26) based on the first step of balance recovery after a lateral balance perturbation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Computed tomography scans to quantify lean tissue and intramuscular adipose tissue (IMAT) areas in the hip abductor, hip abductor isokinetic torque, and first step length. RESULTS: Medial steppers took medial steps in 71.1% of trials versus 4.6% of trials with cross-steps. The cross-steppers when compared with medial steppers, had lower hip abductor IMAT (24.7±0.7% vs 29.9±2.8%; P<.05), greater abductor torque (63.3±3.6Nm vs 48.4±4.1Nm; P<.01), and greater normalized first step length (.75±.03 vs .43±.08; P<.001). There was no difference in hip abductor lean tissue between the groups (P>.05). CONCLUSIONS: Our findings suggest that older adults who initially use a medial step to recover lateral balance have lower hip abductor torque and may be less able to execute a biomechanically more stable cross-step. This may be related to increased IMAT levels. Assessments and interventions for enhancing balance and decreasing fall risk should take the role of the hip abductor into account.

Sarcopenia and Physical Function in Middle-Aged and Older Stroke Survivors.

OBJECTIVES: To determine the prevalence of sarcopenia in stroke survivors using different methodologies, and compare a subset of the stroke group to age-, sex-, and body mass index (BMI)-matched nonstroke control counterparts. DESIGN: Cohort study. SETTING: A Veterans Affairs medical center and a university hospital. PARTICIPANTS: Mild to moderately disabled participants >6 months after onset of stroke aged 40 to 84 years (N=190, 61% men, 57% African American; mean BMI ± SEM, 29±1kg/m2). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using 4 established methods: (1) ALM/height2 (ALM/ht2); (2) European Working Group on Sarcopenia in Older Persons; (3) International Working Group on Sarcopenia; and (4) ALM/BMI. RESULTS: Sarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age ±4 years and BMI ±2.5kg/m2 had higher prevalence rates compared with their nonstroke counterparts (13.2% vs 5.3%, P<.0001). ALM/ht2 was related to 6-minute walking speed (r=.28, P<.01) and peak oxygen consumption (L/min: r=.58, P<.0001) for the stroke group. CONCLUSIONS: Stroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race compared with nonstroke individuals.

Effects of Weight Loss with and without Exercise on Regional Body Fat Distribution in Postmenopausal Women.

BACKGROUND/AIMS: The purpose was to determine whether lifestyle interventions have different effects on regional fat in women with normal glucose tolerance vs. impaired glucose tolerance (NGT vs. IGT). METHODS: Changes in glucose metabolism (2-h oral glucose-tolerance tests), android to gynoid fat mass ratio (dual energy X-ray absorptiometry [DXA]), visceral to subcutaneous abdominal fat area ratio (CT), and abdominal to gluteal subcutaneous fat cell weight (FCW; adipose tissue biopsies) were determined in 60 overweight postmenopausal women (45-80 years) following 6 months of weight loss alone (WL; n = 28) or with aerobic exercise (AEX + WL; n = 32). RESULTS: The interventions led to ∼8% decrease in weight, but only the AEX + WL group improved fitness (↑11% in VO2max) and reduced the android-to-gynoid fat mass ratio (↓5%; p < 0.05). Both NGT and IGT groups reduced visceral and subcutaneous abdominal fat areas and abdominal and gluteal FCWs, which related to improvements in homeostatic model assessment (r = 0.34-0.42) and 2-h glucose (r = 0.34-0.35), respectively (p < 0.05). The decline in FCW was 2× greater in women with IGT following WL (p < 0.05). The ratios of abdominal-to-gluteal FCW did not change following either intervention. CONCLUSIONS: The mechanisms by which WL with and without exercise impact regional fat loss should be explored as reductions in abdominal fat area and subcutaneous FCW appear to influence glucose metabolism. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.