Vitamin D Supplementation and Muscle Power, Strength and Physical Performance in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL [<50 nmol/L]) have been associated with muscle weakness and impaired physical performance in observational studies. However, the effect of vitamin D supplementation on changes in muscle strength and physical performance in randomized controlled trials has been mixed. OBJECTIVES: To determine the effect of daily vitamin D supplementation on leg power, strength, and physical performance in low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL. METHODS: In this double-blind, randomized controlled trial, 136 low-functioning [Short Physical Performance Battery (SPPB) scores ≤10] adults aged 65-89 y with 25(OH)D concentrations of 18 to <30 ng/mL were randomly assigned to 2000 IU/d vitamin D3 or placebo for 12 mo. Lower-extremity leg power (primary outcome), leg and grip strength, SPPB, timed up and go (TUG), postural sway, and gait velocity and spatiotemporal parameters (secondary outcomes) were assessed at baseline, 4 and 12 mo. A subset (n = 37) also underwent a muscle biopsy at baseline and 4 mo and muscle fiber composition and contractile properties were assessed. RESULTS: Participants' mean ± SD age and SPPB scores at baseline were 73.4 ± 6.3 y and 7.8 ± 1.8, respectively. Mean ± SD 25(OH)D concentrations at baseline and 12 mo were 19.4 ± 4.2 ng/mL and 28.6 ± 6.7 ng/mL in the vitamin D group and 19.9 ± 4.9 ng/mL and 20.2 ± 5.0 ng/mL in the placebo group for a mean ± SE difference of 9.1 ± 1.1 ng/mL (P < 0.0001). However, there were no differences in change in leg power, leg or grip strength, SPPB score, TUG, postural sway, or gait velocity and spatiotemporal parameters by intervention group over 12 mo or muscle fiber composition and contractile properties over 4 mo. CONCLUSIONS: In low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL, randomization to 2000 IU/d vitamin D3 did not result in improvements in leg power, strength, or physical performance or muscle fiber composition and contractile properties. This trial was registered at clinicaltrials.gov as NCT02015611.

Preserving older adults' routine outdoor activities in contrasting neighborhood environments through a physical activity intervention.

While neighborhood design can potentially influence routine outdoor physical activities (PA), little is known concerning its effects on such activities among older adults attempting to increase their PA levels. We evaluated the effects of living in neighborhoods differing in compactness on changes in routine outdoor activities (e.g., walking, gardening, yard work) among older adults at increased mobility disability risk participating in the LIFE-Pilot PA trial (2003-07; ages 70-89years; from Dallas, TX, San Francisco Bay area, Pittsburgh, PA, and Winston-Salem, NC). Analyses were conducted on the 400 LIFE-Pilot participants randomized to a one-year endurance-plus-strengthening PA intervention or health education control that completed one-year PA assessment (CHAMPS questionnaire). Outcomes of interest were exercise and leisure walking, walking for errands, and moderate-intensity gardening. Neighborhood compactness was assessed objectively using geographic information systems via a subsequent grant (2008-12). PA increased weekly exercise and leisure walking relative to control, irrespective of neighborhood compactness. However, walking for errands decreased significantly more in PA relative to control (net mean [SD] difference=16.2min/week [7.7], p=0.037), particularly among those living in less compact neighborhoods (net mean [SD] difference=29.8 [10.8] minutes/week, p=0.006). PA participants living in less compact neighborhoods maintained or increased participation in gardening and yard work to a greater extent than controls (net mean [SD] difference=29.3 [10.8] minutes/week, p=0.007). The results indicate that formal targeting of active transport as an adjunct to structured PA programs may be important to diminish potential compensatory responses in functionally impaired older adults. Structured endurance-plus-strengthening PA may help older adults maintain or increase such routine activities over time. TRIAL REGISTRATION: clinicaltrials.gov Identifier=NCT01072500.

Effects of Physical Activity Intervention on Physical and Cognitive Function in Sedentary Adults With and Without Diabetes.

BACKGROUND: Type 2 diabetes mellitus may alter the effect of physical activity on physical and cognitive function. METHODS: The Lifestyle Interventions and Independence for Elders (LIFE) trial randomized controlled clinical trial of physical activity intervention (walking, resistance training, and flexibility exercises) enrolled adults aged 70-89 years who were sedentary and non-demented and who had functional limitations. Standardized measures of physical and cognitive function were collected an average of 2 years post-randomization. Differences between the intervention and control groups from 415 individuals with diabetes and 1,061 individuals without diabetes were contrasted with analyses of covariance. RESULTS: At 24 months, assignment to the physical activity intervention resulted in 0.019 m/s relatively faster average 400-meter gait speeds (p = .007 overall) both for individuals with and without diabetes (intervention × diabetes interaction p = .99). No benefits were seen on scores from a physical performance battery. Performance on cognitive tests was better among participants assigned to the physical activity intervention compared with control only for those with diabetes, particularly for global cognitive function (p = .02) and delayed memory (p = .005), with mean [95% confidence intervals] for benefit from physical activity intervention of 0.114 [0.007,0.111] and 0.208 [0.030,0.387] standard deviations, respectively. CONCLUSIONS: Physical activity intervention improved the gait speed of older, sedentary individuals with and without diabetes. The cognitive function benefits occurred among participants with, but not without, diabetes. The mechanisms through which physical activity affects physical and cognitive function in older adults may differ for individuals by diabetes status.

Effect of a Long-Term Physical Activity Intervention on Resting Pulse Rate in Older Persons: Results from the Lifestyle Interventions and Independence for Elders Study.

OBJECTIVES: To assess the utility of a long-term physical activity (PA) intervention for reducing resting pulse rate (RPR) in older persons. DESIGN: Community. SETTING: Lifestyle Interventions and Independence for Elders Study. PARTICIPANTS: Individuals aged 70 to 89 (N = 1,635, 67.2% women) were randomized to a moderate-intensity PA intervention (n = 818) or a health education-based successful aging (SA) intervention (n = 817). MEASUREMENTS: RPR was recorded at baseline and 6, 18, and 30 months. Longitudinal changes in RPR of intervention groups were compared using a mixed-effects analysis of covariance model for repeated-measure outcomes, generating least squares means with standard errors (SEs) or 95% confidence intervals (CIs). RESULTS: Mean duration of the study was 2.6 years (median 2.7 years, interquartile range 2.3-3.1 years). The average effect of the PA intervention on RPR over the course of the study period was statistically significant but clinically small (average intervention difference = 0.84 beats/min; 95% CI = 0.17-1.51; Paverage = .01), with the most pronounced effect observed at 18 months (PA, 66.5 beats/min (SE 0.32 beats/min); SA, 67.8 beats/min (SE 0.32 beats/min); difference = 1.37 beats/min, 95% CI = 0.48-2.26 beats/min). The relationship became somewhat weaker and was not statistically significant at 30 months. There were no significant differences between several prespecified subgroups. CONCLUSION: A long-term moderate-intensity PA program was associated with a small and clinically insignificant slowing of RPR in older persons. Whether PA can deliver a beneficial reduction in RPR requires further examination in older adults.

Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.

Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study).

OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and Independence for Elders (LIFE) study). SETTING: Eight centers across the United States, February 2010 to December 2011. PARTICIPANTS: 1635 sedentary adults aged 70-89 years with functional limitations, defined as a short physical performance battery score ≤ 9, but who were able to walk 400 m. INTERVENTIONS: A permuted block algorithm stratified by field center and sex was used to allocate interventions. Participants were randomized to a structured, moderate intensity physical activity program (n=818) conducted in a center (twice a week) and at home (3-4 times a week) that included aerobic, strength, flexibility, and balance training activities, or to a health education program (n=817) consisting of workshops on topics relevant to older people and upper extremity stretching exercises. MAIN OUTCOME MEASURES: Serious fall injuries, defined as a fall that resulted in a clinical, non-vertebral fracture or that led to a hospital admission for another serious injury, was a prespecified secondary outcome in the LIFE Study. Outcomes were assessed every six months for up to 42 months by staff masked to intervention assignment. All participants were included in the analysis. RESULTS: Over a median follow-up of 2.6 years, a serious fall injury was experienced by 75 (9.2%) participants in the physical activity group and 84 (10.3%) in the health education group (hazard ratio 0.90, 95% confidence interval 0.66 to 1.23; P=0.52). These results were consistent across several subgroups, including sex. However, in analyses that were not prespecified, sex specific differences were observed for rates of all serious fall injuries (rate ratio 0.54, 95% confidence interval 0.31 to 0.95 in men; 1.07, 0.75 to 1.53 in women; P=0.043 for interaction), fall related fractures (0.47, 0.25 to 0.86 in men; 1.12, 0.77 to 1.64 in women; P=0.017 for interaction), and fall related hospital admissions (0.41, 0.19 to 0.89 in men; 1.10, 0.65 to 1.88 in women; P=0.039 for interaction). CONCLUSIONS: In this trial, which was underpowered to detect small, but possibly important reductions in serious fall injuries, a structured physical activity program compared with a health education program did not reduce the risk of serious fall injuries among sedentary older people with functional limitations. These null results were accompanied by suggestive evidence that the physical activity program may reduce the rate of fall related fractures and hospital admissions in men.Trial registration ClinicalsTrials.gov NCT01072500.

Tissue-Specific and Genetic Regulation of Insulin Sensitivity-Associated Transcripts in African Americans.

Integrative multiomics analyses of adipose and muscle tissue transcripts, S, and genotypes revealed novel genetic regulatory mechanisms of insulin resistance in African Americans.

Relationships between mitochondrial content and bioenergetics with obesity, body composition and fat distribution in healthy older adults.

BACKGROUND: Mitochondrial function declines with age; however, the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults. METHODS: 25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of age, with a BMI range of 18-35 kg/m(2), participated in this study. Vastus lateralis biopsies were analyzed for citrate synthase (CS) activity and succinate mediated respiration of isolated mitochondria. Whole body and thigh composition were measured by DXA and CT. HOMA-IR was calculated using fasting glucose and insulin as an estimate of insulin sensitivity. RESULTS: Similar to reports in middle-aged adults, skeletal muscle CS activity was negatively correlated with BMI (R = -0.43) in our cohort of older adults. Higher total and thigh adiposity were correlated with lower CS activity independent of BMI (R = -0.50 and -0.71 respectively). Maximal complex 2 driven mitochondrial respiration was negatively correlated with lower body adiposity in males (R = -0.66). In this cohort of non-diabetic older adults, both HOMA-IR and insulin were positively correlated with CS activity when controlling for BMI (R = 0.57 and 0.66 respectively). CONCLUSIONS: Adiposity and body composition are correlated with skeletal muscle mitochondrial content and electron transport chain function in healthy, sedentary, community dwelling, older adults. Specific relationships of mitochondrial bioenergetics with gender and insulin sensitivity are also apparent. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01049698.

Delivery of a Vitamin D Intervention in Homebound Older Adults Using a Meals-on-Wheels Program: A Pilot Study.

OBJECTIVES: To assess the feasibility of a vitamin D intervention delivered through a Meals-on-Wheels (MOW) program to improve 25-hydroxyvitamin D (25(OH)D) concentrations and reduce falls in homebound older adults. DESIGN: Single-blind, cluster randomized trial. SETTING: MOW, Forsyth County, North Carolina. PARTICIPANTS: Community-dwelling homebound adults aged 65 to 102 (N = 68). INTERVENTION: MOW clients were randomized to vitamin D3 (100,000 IU/month; n = 38) or active placebo (400 IU vitamin E/month; n = 30) according to MOW delivery route. MEASUREMENTS: Serum 25(OH)D was assessed at baseline and 5-month follow-up; proportions of participants in 25(OH)D categories were compared using Fisher exact test. Falls were assessed using monthly fall calendars, and rate of falls was estimated using negative binomial generalized estimating equation models. RESULTS: Mean ± standard deviation 25(OH)D concentrations were 20.9 ± 11.5 ng/mL at baseline, with 57% having 25(OH)D concentrations less than 20 ng/mL. Retention and adherence were high (>90%). After the 5-month intervention, only one of 34 participants randomized to vitamin D3 had 25(OH)D concentrations less than 20 ng/mL, compared with 18 of 25 participants randomized to placebo (P < .001). In unadjusted analyses, the rate of falls over 5 months was not significantly different according to intervention group (risk ratio (RR) = 0.48, 95% confidence interval (CI) = 0.19-1.19), but after adjustment for sex, race, season of year, baseline 25(OH)D status, and history of falls, participants randomized to vitamin D3 had a lower rate of falling than those randomized to placebo (RR = 0.42, 95% CI = 0.21-0.87). CONCLUSION: A vitamin D intervention delivered through MOW was feasible, resulting in improvements in 25(OH)D concentrations and a lower rate of falls in adjusted analyses. Further research is needed to validate the reduction in falls from this type of intervention.

Preparation and respirometric assessment of mitochondria isolated from skeletal muscle tissue obtained by percutaneous needle biopsy.

Respirometric profiling of isolated mitochondria is commonly used to investigate electron transport chain function. We describe a method for obtaining samples of human Vastus lateralis, isolating mitochondria from minimal amounts of skeletal muscle tissue, and plate based respirometric profiling using an extracellular flux (XF) analyzer. Comparison of respirometric profiles obtained using 1.0, 2.5 and 5.0 µg of mitochondria indicate that 1.0 µg is sufficient to measure respiration and that 5.0 µg provides most consistent results based on comparison of standard errors. Western blot analysis of isolated mitochondria for mitochondrial marker COX IV and non-mitochondrial tissue marker GAPDH indicate that there is limited non-mitochondrial contamination using this protocol. The ability to study mitochondrial respirometry in as little as 20 mg of muscle tissue allows users to utilize individual biopsies for multiple study endpoints in clinical research projects.

The role of primary care providers in managing falls.

Falls threaten the ability of older adults to live independently in the community. Fortunately, national and state organizations have created tools that allow primary care providers to easily assess fall risk, and small changes in practice patterns can provide patients with the resources necessary to prevent falls, thus helping to reverse a costly, deadly epidemic.

Utilizing a Meals on Wheels program to teach falls risk assessment to medical students.

Falls are a critical public health issue for older adults, and falls risk assessment is an expected competency for medical students. The aim of this study was to design an innovative method to teach falls risk assessment using community-based resources and limited geriatrics faculty. The authors developed a Fall Prevention Program through a partnership with Meals-on-Wheels (MOW). A 3rd-year medical student accompanies a MOW client services associate to a client's home and performs a falls risk assessment including history of falls, fear of falling, medication review, visual acuity, a Get Up and Go test, a Mini-Cog, and a home safety evaluation, reviewed in a small group session with a faculty member. During the 2010 academic year, 110 students completed the in-home falls risk assessment, rating it highly. One year later, 63 students voluntarily completed a retrospective pre/postsurvey, and the proportion of students reporting moderate to very high confidence in performing falls risk assessments increased from 30.6% to 87.3% (p < .001). Students also reported using most of the skills learned in subsequent clerkships. A single educational intervention in the MOW program effectively addressed geriatrics competencies with minimal faculty effort and could be adopted by many medical schools.

Regional adipose tissue hormone/cytokine production before and after weight loss in abdominally obese women.

OBJECTIVE: To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. METHODS: Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: ∼2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. RESULTS: The intervention resulted in significant weight loss (-10.1 ± 0.7 kg, P < 0.001). At baseline, gene expression of adiponectin were higher (P < 0.01), and gene expression and release of IL-6 were lower (both P < 0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P < 0.05-0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P < 0.05). CONCLUSION: A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity.

Utility of a congregational health assessment to identify and direct health promotion opportunities in churches.

PURPOSE: The church is a focal point for health education efforts in minority communities due to its status as one of the most prominent and stable institutions. This paper highlights an approach for identifying health programming targets in minority churches. METHODS: Twenty-four churches participated in a one-year Health Ministry Institute (HMI), designed to help churches develop sustainable ministries for health promotion. HMI attendees were instructed on conducting a Congregational Health Assessment (CHA) to identify prevalent health conditions and related behaviors in their churches. Churches collected CHAs over a one-month period. Data were analyzed and results were discussed during a HMI session and used to prioritize health-related issues that could be addressed at individual churches. RESULTS: Seventeen churches (71%) returned surveys (n=887; 70% female; 73% African American). Prevalent health conditions, participation in health-promoting behaviors, interest in learning to live healthy, and interest in health ministry activities were identified using the CHA. CONCLUSIONS: The CHA shows promise for health assessment, and can be used to identify health issues that are of interest and relevance to church congregants and leaders. The CHA may assist churches with implementing effective and sustainable programs to address the identified health issues.

Teaching medical student geriatrics competencies in 1 week: an efficient model to teach and document selected competencies using clinical and community resources.

The Association of American Medical Colleges (AAMC) and the John A. Hartford Foundation published geriatrics competencies for medical students in 2008 defining specific knowledge and skills that medical students should be able to demonstrate before graduation. Medical schools, often with limited geriatrics faculty resources, face challenges in teaching and assessing these competencies. As an initial step to facilitate more-efficient implementation of the competencies, a 1-week geriatrics rotation was developed for the third year using clinical, community, and self-directed learning resources. The Wake Forest University School of Medicine Acute Care for the Elderly Unit serves as home base, and each student selects a half-day outpatient or long-term care experience. Students also perform a home-based falls-risk assessment with a Meals-on-Wheels client. The objectives for the rotation include 20 of the 26 individual AAMC competencies and specific measurable tracking tasks for seven individual competencies. In the evaluation phase, 118 students completed the rotation. Feedback was positive, with an average rating of 7.1 (1 = worst, 10 = best). Students completed a 23-item pre- and post-knowledge test, and average percentage correct improved by 15% (P < .001); this improvement persisted at graduation (2 years after the pretest). On a 12-item survey of attitudes toward older adults, improvement was observed immediately after the rotation that did not persist at graduation. Ninety-seven percent of students documented completion of the competency-based tasks. This article provides details of development, structure, evaluation, and lessons learned that will be useful for other institutions considering a brief, concentrated geriatrics experience in the third year of medical school.

Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial.

BACKGROUND: Exercise intensity may affect the selective loss of abdominal adipose tissue. OBJECTIVE: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. DESIGN: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m(2)): 25-40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (approximately 400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45-50% (moderate-intensity) or 70-75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. RESULTS: Average weight loss for the 95 women who completed the study was 12.1 kg (+/-4.5 kg) and was not significantly different across groups. Maximal oxygen uptake ( O(2)max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (approximately 25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O(2)max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. CONCLUSION: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at (ClinicalTrials.gov) as: NCT00664729.