Debra L. Waters

Predictors of skeletal muscle mass in elderly men and women.

BACKGROUND Elderly men and women lose muscle mass and strength with increasing age. Decreased physical activity, hormones, malnutrition and chronic disease have been identified as factors contributing to this loss. There are few data, however, for their multivariate associations with muscle mass and strength. This study analyzes these associations in a cross-sectional sample of elderly people from the New Mexico Aging Process Study. METHODS Data collected in 1994 for 121 male and 180 female volunteers aged 65-97 years of age enrolled in The New Mexico Aging Process Study were analyzed. Body composition was measured using dual energy X-ray absorptiometry; dietary intake from 3 day food records; usual physical activity by questionnaire; health status from annual physical examinations; and serum testosterone, estrone, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF1) from radioimmunoassays of fasting blood samples. Statistical analyses included partial correlation and stepwise multiple regression. RESULTS The muscle mass and strength (adjusted for knee height) decreased with increasing age in both sexes. The muscle mass was significantly associated with serum free-testosterone, physical activity, cardiovascular disease, and IGF1 in the men. In the women, the muscle mass was significantly associated with total fat mass and physical activity. Age was not associated significantly with muscle mass after controlling for these variables. Grip strength was associated with age independent of muscle mass in both sexes. Estrogen (endogenous and exogenous) was not associated with muscle mass or strength in women. CONCLUSIONS Age-related loss of muscle mass and strength occurs in relatively healthy, well-nourished elderly men and women and has a multifactorial basis. Sex hormone status is an important factor in men but not in women. Physical activity is an important predictor of muscle mass in both sexes.

Recombinant Human Growth Hormone, Insulin-like Growth Factor 1, and Combination Therapy in AIDS-Associated Wasting: A Randomized, Double-Blind, Placebo-Controlled Trial

Wasting associated with the acquired immunodeficiency syndrome (AIDS) is a serious complication of human immunodeficiency virus (HIV) infection that causes progressive loss of both lean body mass and, more variably, fat mass [1-4]. The pathogenesis is probably multifactorial and includes the underlying viral infection, tissue cytokines, intercurrent infections, and poor intake of calories [1, 2]. Recombinant human insulin-like growth factor 1 (rhIGF-1) alone and recombinant human growth hormone (rhGH) alone have been administered to humans during various catabolic states, including fasting, the period immediately after surgery, and trauma, and have had positive effects on lean body mass [5-7]. The beneficial effects of rhGH on body composition and metabolism are reportedly mediated by increased levels of IGF-1 [4, 5]. Furthermore, animal studies have shown that rhIGF-1 has beneficial effects on lymphopoieses [8]. Limited studies of rhGH or rhIGF-1 treatment alone in patients with AIDS have also been promising, resulting in an increase in circulating IGF-1 levels, lean body mass, and muscle function [9-11]. We hypothesized that treating AIDS-associated wasting with rhIGF-1, alone or in combination with rhGH, would reverse the catabolic effects characteristic of this wasting. We further hypothesized that if rhGH therapy increased lean body mass, then physical strength, immune function, and quality of life would improve. We therefore did a randomized, double-blind, placebo-controlled trial to assess the effects of rhGH and rhIGF-1 therapy in patients with AIDS-associated wasting. The primary end points were changes in weight and lean body mass. The secondary end points were changes in muscle function, immune status, quality of life, and protein catabolism. The Institutional Review Boards of the University of New Mexico and the University of Texas Southwestern Medical Center approved the study, and all patients gave written informed consent before entering the study. Methods Patients We recruited 60 patients (58 men and 2 women) with AIDS (as defined by the Centers for Discase Control and Prevention [12]), unexplained wasting (defined as weight loss 10% of the weight before diagnosis or body mass index 19.8 kg/m2), and a CD4 count less than 200 cells/mm3. Weight before diagnosis was defined as the weight that an adult patient maintained for at least 2 years during the time the patient believed that he or she was healthy. In New Mexico, patients were recruited by postings at the University of New Mexico Hospital Infectious Disease Clinic and Veterans Administration Hospital and by physician referral from private practices in Albuquerque and Santa Fe. In Texas, patients were recruited from the University of Texas Southwestern Medical Center at Dallas, a collaborating institution, and private practices throughout the Southwest. In addition, an advertisement was placed in the directory of the American Federation for AIDS Research. The patients were admitted to the University of New Mexico Clinical Research Center for a 2-day inpatient screening assessment. This assessment included physical examination, neurologic examination, electrocardiography, and chest radiography. Additional inclusion criteria were a hematocrit of 0.28 or greater, negative result of a pregnancy test (in women), negative 7-day blood culture for Mycobacterium avium intracellulare within 4 weeks before study entry, negativity for cryptococcal antigen in serum within 4 weeks before study entry, and a chest radiograph showing no evidence of acute cardiopulmonary disease within 28 days before study entry. Exclusion criteria were body mass index of 26.0 kg/m2 or greater, opportunistic infection that resolved less than 4 weeks before study entry, diarrhea (defined as five or more bowel movements per day or identification of an enteric pathogen), history of endocrine disease associated with hypoglycemia or hyperglycemia, any disorder associated with moderate or severe edema, history of cancer within 3 years of study entry, active Kaposi sarcoma, diagnosed cardiovascular disease (including congestive heart failure and cardiomyopathy), medically significant liver dysfunction (serum alanine aminotransferase level > 200 IU, total bilirubin level > 51.3 mmol/L) and renal dysfunction (creatinine level > 176.8 mmol/L). Baseline dietary histories were analyzed; at study entry, all patients were consuming at least 25 kcal/kg of body weight and none was receiving intravenous or tube feeding. None had received therapy with anabolic or catabolic agents, including interferon, megestrol, dronabinol, oxandrolone, and corticosteroids, within 30 days of study entry. No patient had received any experimental agent or procedure within 30 days of enrollment other than prophylactic antimicrobial therapy directed at fungal, bacterial, viral, mycobacterial, or parasitic infections. All patients had been receiving antiretroviral therapy for at least 3 months before study entry and received prophylaxis for Pneumocystis carinii throughout the treatment period. Genentech, Inc. (South San Francisco, California), randomly assigned the 60 patients into four groups of 15 patients each so that balance was maintained across the groups with respect to body mass index, CD4 count, type of antiretroviral therapy, and age. The type of antiretroviral therapy was divided into five categories: zidovudine alone, didanosine alone, simultaneous administration of zidovudine and didanosine, simultaneous administration of zidovudine and zalcitabine, and other. The schedule for the subcutaneously injected therapy was as follows: Group 1 received 1.4 mg of rhGH once daily and 1 mL of placebo twice daily; group 2 received 5 mg of rhIGF-1 twice daily and 1 mL of placebo once daily; group 3 received 5 mg of rhIGF-1 twice daily and 1.4 mg of rhGH once daily; and group 4 received 1 mL of placebo three times daily. All patients received three subcutaneous injections per day for 12 weeks. Both patients and clinicians were blinded to treatment group assignments. The rhGH dosage used in this study was approximately one half the dosage used in our previous study [9]. The decision to use this dosage was based on the 2 2 analysis of variance (ANOVA) design and concern about the potential for increased incidence and severity of side effects if full doses of rhGH and rhIGF-1 were used in the patients receiving rhGH plus rhIGF-1. Patients were withdrawn from the study if they did not administer all three injections each day for 7 continuous days throughout the treatment period. Injection compliance was assessed by counting vials and interviewing the study clinician during assessment visits. In addition, IGF-1 levels were monitored in all patients and were compared with values at baseline and those in placebo recipients. The intended duration of all treatments was 12 weeks. Body Composition Lean body mass, fat mass, and percentage of body fat were measured by using dual-energy x-ray absorptiometry (Hologic QDR-1000/W, Waltham, Massachusetts), as described elsewhere [13]. Total Body Water We measured total body water using bioelectric impedance analysis (model 106, bioelectrical impedance analysis, RJL Systems, Detroit, Michigan). Testing was done between 1300 and 1500 hours, and all patients were fed and well hydrated before testing. We calculated body water by fitting the impedance measurements of resistance and reactance into previously derived prediction equations [14]. Protein Catabolism Protein catabolism was estimated by turnover of [2H5]phenylalanine (Cambridge Isotope Laboratories, Woburn, Massachusetts), as described elsewhere [15, 16]. The plasma phenylalanine level was measured by using gas chromatography mass spectrometry after being derivatized to its t-butyldimethylsilyl ester [17]. The concentration and level of [2H5]phenylalanine in plasma were analyzed by using multiple ion detection under electron-impact ionization conditions [17]. Muscle Function Computerized isotonic dynamometry (Baltimore Therapeutic Equipment, Baltimore, Maryland) was used to evaluate maximal voluntary contraction and maximum power (20%, 40%, and 60% maximal voluntary contraction) for a knee extension and a compound movement of the upper body. Quality of Life We measured quality of life using a self-administered 36-item Medical Outcomes Study questionnaire, which was previously validated in HIV-positive patients with AIDS-associated complex [18]. We accounted for missing values by averaging scores across completed items in the same scale for a particular patient. Eleven domains and three generalized domains were analyzed: 1) Total score was the average of the scores for all 36 questions; 2) functional status was the average of the scores in the domains for physical functioning, role functioning, social functioning, and cognitive functioning; and 3) well-being was the average of the scores in the domains for pain, mental health, energy and fatigue, health distress, and quality of life. Endocrine Assays Serum insulin levels were measured by using double-antibody radioimmunoassay (Pharmacia Diagnostics AB, Piscataway, New Jersey), and growth hormone levels were measured by using Tandem-R human growth hormone immunoradiometric assay (Hybritech, Inc., San Diego, California). Total IGF-1 levels were measured by double-antibody radioimmunoassay using rabbit antihuman IGF-1 antibody generated by Peter Gluckman (Auckland, New Zealand) at Genentech, Inc. Immunologic Studies Levels of HIV p24 antigen were measured in serum after acid dissociation by solid-phase sand-wich-type immunoassay that used a signal amplification technique (acid dissociated enzyme-linked immunoassay, DuPont Co., Boston, Massachusetts) [19]. CD3, CD4, and CD8 counts and percentage of total lymphocytes were measured in Ficol-separated peripheral blood mononuclear cell by flow cytometry using appropriate monoclonal antibodies and FACscan IV (Becton-Dickinson, Mountain Vi

Advantages of dietary, exercise-related, and therapeutic interventions to prevent and treat sarcopenia in adult patients: an update

Sarcopenia is the loss of skeletal muscle mass and function with aging. Although the term sarcopenia was first coined in 1989, its etiology is still poorly understood. Moreover, a consensus for defining sarcopenia continues to elude us. Sarcopenic changes in the muscle include losses in muscle fiber quantity and quality, alpha-motor neurons, protein synthesis rates, and anabolic and sex hormone production. Other factors include basal metabolic rate, increased protein dietary requirements, and chronic inflammation secondary to age-related changes in cytokines and oxidative stress. These changes lead to decreased overall physical functioning, increased frailty, falls risk, and ultimately the loss of independent living. Because the intertwining relationships of these factors are complex, effective treatment options are still under investigation. The published data on sarcopenia are vast, and this review is not intended to be exhaustive. The aim of this review is to provide an update on the current knowledge of the definition, etiology, consequences, and current clinical trials that may help address this pressing public health problem for our aging populations.

Sarcopenia and Obesity

Four body composition phenotypes exist in older adults: normal, sarcopenic, obese, and a combination of sarcopenic and obese. There is no consensus, however, on the definitions and classifications of these phenotypes and their etiology and consequences continue to be debated. The lack of standard definitions, particularly for sarcopenia and sarcopenic obesity, creates challenges for determining prevalence across different populations. The etiology of these phenotypes is multifactorial with complex covariate relationships. This review focuses on the current literature addressing the classification, prevalence, etiology, and correlates of sarcopenia, obesity, and the combination of sarcopenia and obesity, referred to as sarcopenic obesity.

Effects of estradiol on substrate turnover during exercise in amenorrheic females.

The purpose of this investigation was to determine the effects of transdermal estradiol (E2) replacement on substrate utilization during exercise. Amenorrheic females (N = 6) performed three exercise trials following 72 h of placebo (C 72) and 72 and 144 h of medicated transdermal estradiol (E2) treatment (E2 72 and E2 144). Exercise involved 90 min of treadmill running at 65% VO2max followed by timed exercise to exhaustion at 85% VO2max. Resting blood samples were obtained for glucose, insulin, free fatty acids (FFA), and E2. Exercise blood samples were obtained for E2, lactate, epinephrine, and norepinephrine. Rates of appearance and disposal were calculated for glucose and glycerol using a primed, continuous infusion of [6,6-2H] glucose and [2H5] glycerol. Medicated transdermal placement increased E2 significantly at rest, before exercise (35.03 +/- 12.3, 69.5 +/- 20.1, and 73.1 +/- 31.6 pg.mL-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Resting FFA increased significantly following E2 treatment (0.28 +/- 0.16, 0.41 +/- 0.27, and 0.40 +/- 0.21 mmol.L-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Glucose Ra was significantly decreased during exercise as a result of E2 replacement (21.9 +/- 7.7, 18.9 +/- 6.2, and 18.9 +/- 5.6 mumol.kg-1.min-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Average glucose Rd also decreased during exercise as a result of E2 replacement (21.3 +/- 7.8, 18.5 +/- 6.4, and 18.6 +/- 5.8 mumol.kg-1.min-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). However, the estimated relative contribution of plasma glucose and muscle glycogen to total carbohydrate oxidation was similar among the trials. Epinephrine values were significantly lower late in exercise during the E2 72 and E2 144 trials, compared with the C 72 trial (P < 0.05). These results indicate that elevated E2 levels can alter glucose metabolism at rest and during moderate intensity exercise as a result of decreased gluconeogenesis, epinephrine secretion, and/or glucose transport.

Weight loss in obese adults 65 years and older: A review of the controversy

Obesity in older adults is ubiquitous in many developed countries and is related to various negative health outcomes, making it an important public health target for intervention. However, treatment approaches for obesity in older adults remain controversial due to concerns surrounding the difficulty of behavior change with advancing age, exacerbating the age-related loss of skeletal muscle and bone, and the feasibility of long-term weight maintenance and related health consequences. This review serves to systematically examine the evidence regarding weight loss interventions with a focus on obese (body mass index 30kg/m(2) and above) older adults (aged 65years and older) and some proposed mechanisms associated with exercise and caloric restriction (lifestyle intervention). Our findings indicate that healthy weight loss in this age group can be achieved through lifestyle interventions of up to a one-year period. Most interventions reviewed reported a loss of lean body mass and bone mineral density with weight loss. Paradoxically muscle quality and physical function improved. Inflammatory molecules and metabolic markers also improved, although the independent and additive effects of exercise and weight loss on these pathways are poorly understood. Using our review inclusion criteria, only one small pilot study investigating long-term weight maintenance and associated health implications was found in the literature. Future research on lifestyle interventions for obese older adults should address the loss of bone and lean body mass, inflammatory mechanisms, and include sufficient follow-up to assess long-term weight maintenance and health outcomes.

Using accelerometers and GPS units to identify the proportion of daily physical activity located in parks with playgrounds in New Zealand children

OBJECTIVE To identify the proportion of childrens physical activity occurring in public parks with playgrounds. METHODS Children (n=184) aged 5 to 10 years were recruited from schools located in two low socio-economic status communities in Dunedin, New Zealand. Accelerometers (Actigraph GT1M) and global positioning system units (Globalsat DG-100) were used to quantify and identify where physical activity had occurred over a 7-day period. Cross-sectional data were collected October to December 2007 (southern hemisphere spring) and the childs height and weight were measured at school. RESULTS At least 84% of participants had accelerometer and global positioning system data available for five or more hourly periods per day, for at least 4 days. Overall, 1.9% of recorded activity took place at city parks (95% confidence interval: 1.4, 2.4), although this was 2.7% (95% confidence intervals: 0.7, 4.6) among obese children. CONCLUSIONS Accelerometers and GPS data was able to be successfully recorded and matched among this age group. The proportion of childrens activity taking place in parks with playgrounds was low, although this may still be important for some subgroups.

A Randomized Controlled Trial to Investigate the Effects of Water-Based Exercise to Improve Falls Risk and Physical Function in Older Adults With Lower-Extremity Osteoarthritis

OBJECTIVE To investigate the efficacy of a water-based exercise program specifically targeting balance to reduce falls risk and improve measures of balance and physical function in older adults with osteoarthritis (OA). DESIGN Randomized controlled trial. SETTING Community. PARTICIPANTS Persons (N=39; mean±SD age, 74±6y; 26 women) with mild to moderate OA and at risk for falling met study criteria, were measured at baseline, and were randomly assigned to the intervention (n=23) and control groups (n=16). INTERVENTIONS Water-based program (12wk, twice weekly; intervention group) or a time-matched computer training program (control group). MAIN OUTCOME MEASURE The primary outcome was the short-form Physiological Profile Assessment (PPA). Secondary outcomes included the Step Test, Timed Up and Go Test, Western Ontario and McMaster Universities OA Index (Likert 3.0 version), Arthritis Impact Measurement Scales 2, and Activity-specific Balance Confidence Scale. RESULTS No statistically significant between-group differences were found for any outcome measured (n=35; 4 lost to follow-up). Within-group analysis indicated that Step Test results improved significantly in both groups (mean change: control group, left leg, 2.07; 95% confidence interval, 3.19-.95; P=.002; intervention group, 2.14; 95% confidence interval, 3.20-1.08; P=.000). Two PPA item scores (reaction time, contrast sensitivity) improved significantly (86.83; 95% confidence interval, 9.86-163.79; P=.03; 1.43; 95% confidence interval, 2.35-.50; P=.005, respectively) in the control group, resulting in a lower falls risk score. CONCLUSIONS Water-based exercise did not reduce falls risk in our sample compared with attending a computer skills training class. Our study is, to our knowledge, the first to compare water-based exercise in this population with a control group that attended a time-dose-equivalent seated community-based activity. Whether gaining computer skills and going out into the community twice weekly is adequate stimulus to reduce falls risk in people with OA requires further investigation.

Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults

BACKGROUND Obesity impairs cognition and health-related quality of life (HRQOL) in older adults; however, the appropriate treatment of obese older adults remains controversial. OBJECTIVE The objective was to determine the independent and combined effects of weight loss and exercise on cognition, mood, and HRQOL in obese older adults. DESIGN One hundred seven frail, obese older adults were randomly assigned to a control, weight-management (diet), exercise, or weight-management-plus-exercise (diet-exercise) group for 1 y. In this secondary analysis, main outcomes were Modified Mini-Mental State Examination (3MS) and total Impact of Weight on Quality of Life-Lite (IWQOL) scores. Other outcomes included Word Fluency Test, Trail Making Test Parts A and B, and Geriatric Depression Scale (GDS) scores. RESULTS Scores on the 3MS improved more in the diet (mean ± SE: 1.7 ± 0.4), exercise (2.8 ± 0.4), and diet-exercise (2.9 ± 0.4) groups than in the control group (0.1 ± 0.4) (between-group P = 0.0001-0.04); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. Scores on the Word Fluency Test improved more in the exercise (4.1 ± 0.8) and diet-exercise (4.2 ± 0.7) groups than in the control group (-0.8 ± 0.8; both P = 0.001). For the Trail Making Test Part A, scores in the diet-exercise group (-11.8 ± 1.9) improved more than in the control group (-0.8 ± 1.9) (P = 0.001); a similar finding was observed for the Trail Making Test Part B. Scores on the IWQOL improved more in the diet (7.6 ± 1.6), exercise (10.1 ± 1.6), and diet-exercise (14.0 ± 1.4) groups than in the control group (0.3 ± 1.6) (P = 0.0001-0.03); scores in the diet-exercise group improved more than in the diet group but not more than in the exercise group. In the diet-exercise group, peak oxygen consumption and strength changes were independent predictors of 3MS changes; weight and strength changes were independent predictors of IWQOL changes. GDS scores did not change. CONCLUSIONS Weight loss and exercise each improve cognition and HRQOL, but their combination may provide benefits similar to exercise alone. These findings could inform practice guidelines with regard to optimal treatment strategies for obese older adults. This trial was registered atclinicaltrials.govas NCT00146107.

Effectiveness of Tai Chi as a Community-Based Falls Prevention Intervention: A Randomized Controlled Trial

To compare the effectiveness of tai chi and low‐level exercise in reducing falls in older adults; to determine whether mobility, balance, and lower limb strength improved and whether higher doses of tai chi resulted in greater effect.