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1.  Weight Loss, Exercise, or Both and Physical Function in Obese Older Adults 
The New England journal of medicine  2011;364(13):1218-1229.
Obesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial.
In this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weightmanagement (diet) group, an exercise group, or a weight-management-plus-exercise (diet–exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life.
A total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet–exercise group than in the diet group or the exercise group (increases from baseline of 21% vs. 12% and 15%, respectively); the scores in all three of those groups increased more than the scores in the control group (in which the score increased by 1%) (P<0.001 for the between-group differences). Moreover, the peak oxygen consumption improved more in the diet–exercise group than in the diet group or the exercise group (increases of 17% vs. 10% and 8%, respectively; P<0.001); the score on the Functional Status Questionnaire, in which higher scores indicate better physical function, increased more in the diet–exercise group than in the diet group (increase of 10% vs. 4%, P<0.001). Body weight decreased by 10% in the diet group and by 9% in the diet–exercise group, but did not decrease in the exercise group or the control group (P<0.001). Lean body mass and bone mineral density at the hip decreased less in the diet–exercise group than in the diet group (reductions of 3% and 1%, respectively, in the diet–exercise group vs. reductions of 5% and 3%, respectively, in the diet group; P<0.05 for both comparisons). Strength, balance, and gait improved consistently in the diet–exercise group (P<0.05 for all comparisons). Adverse events included a small number of exercise-associated musculoskeletal injuries.
These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone.
PMCID: PMC3114602  PMID: 21449785
2.  Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese post-menopausal women 
Obesity (Silver Spring, Md.)  2011;20(8):1628-1638.
Lifestyle interventions for weight loss are the cornerstone of obesity therapy, yet their optimal design is debated. This is particularly true for postmenopausal women; a population with a high prevalence of obesity yet towards whom fewer studies are targeted. We conducted a year-long, 4-arm randomized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced, low-fat diet (D), a moderate-intensity, facility-based aerobic exercise program (E), or the combination of both interventions (D+E), vs. a no-lifestyle-change control (C) on change in body weight and composition. The group-based dietary intervention had a weight-reduction goal of ≥10%, and the exercise intervention consisted of a gradual escalation to 45 min aerobic exercise 5 d/wk. Participants were predominantly non-Hispanic Whites (85%) with a mean age of 58.0±5.0 years, a mean BMI of 30.9±4.0 kg/m2 and an average of 47.8±4.4% body fat. Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants’ intervention assignment. 399 women completed the trial (91% retention). Using an intention-to-treat analysis, average weight loss at 12 months was −8.5% for the D group (P<0.0001 vs. C), −2.4% for the E group (P=0.03 vs. C), and −10.8% for the D+E group (P<0.0001 vs. C), while the C group experienced a non-significant −0.8% decrease. BMI, waist circumference, and % body fat were also similarly reduced. Among postmenopausal women, lifestyle change involving diet, exercise, or both combined over 1 year improves body weight and adiposity, with the greatest change arising from the combined intervention.
PMCID: PMC3406229  PMID: 21494229
Body weight; body composition; weight-reducing diet; exercise intervention; women
3.  Dietary Weight-Loss and Exercise Effects on Insulin Resistance in Postmenopausal Women 
Comprehensive lifestyle interventions are effective in preventing diabetes and restoring glucose regulation; however, the key stimulus for change has not been identified and effects in older individuals are not established. The aim of the study was to investigate the independent and combined effects of dietary weight-loss and exercise on insulin sensitivity and restoration of normal fasting glucose in mid-aged and older women.
Four-arm RCT, conducted between 2005 and 2009 and data analyzed in 2010.
439 inactive, overweight/obese postmenopausal women. Interventions: Women were assigned to: dietary weight loss (n=118), exercise (n=117), exercise+diet (n=117), or control (n=87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity aerobic activity.
Main outcome measures
12-month change in serum insulin, C-peptide, fasting glucose, and whole body insulin resistance (HOMA-IR).
A significant improvement in HOMA-IR was detected in the diet (−24%, p<0.001) and exercise+ diet (−26%, p<0.001) groups, but not in the exercise (−9%, p=0.22) group compared to controls (−2%); these effects were similar in middle-aged (50–60 years) and older women (aged 60–75 years). Among those with impaired fasting glucose (5.6–6.9 mmol/L) at baseline (n=143; 33%), the odds (95% CI) of regressing to normal fasting glucose after adjusting for weight loss and baseline levels were: 2.5 (0.8, 8.4), 2.76 (0.8, 10.0), and 3.1 (1.0, 9.9) in the diet, exercise+diet, and exercise group, respectively, compared to controls.
Dietary weight loss, with or without exercise, significantly improved insulin resistance. Older women derived as much benefit as did the younger postmenopausal women.
PMCID: PMC3185302  PMID: 21961463
4.  An Exploratory Analysis of the Effects of a Weight Loss Plus Exercise Program on Cellular Quality Control Mechanisms in Older Overweight Women 
Rejuvenation Research  2011;14(3):315-324.
Obese older adults are particularly susceptible to sarcopenia and have a higher prevalence of disability than their peers of normal weight. Interventions to improve body composition in late life are crucial to maintaining independence. The main mechanisms underlying sarcopenia have not been determined conclusively, but chronic inflammation, apoptosis, and impaired mitochondrial function are believed to play important roles. It has yet to be determined whether impaired cellular quality control mechanisms contribute to this process. The objective of this study was to assess the effects of a 6-month weight loss program combined with moderate-intensity exercise on the cellular quality control mechanisms autophagy and ubiquitin-proteasome, as well as on inflammation, apoptosis, and mitochondrial function, in the skeletal muscle of older obese women. The intervention resulted in significant weight loss (8.0 ± 3.9 % vs. 0.4 ± 3.1% of baseline weight, p = 0.002) and improvements in walking speed (reduced time to walk 400 meters, − 20.4 ± 16% vs. − 2.5 ± 12%, p = 0.03). In the intervention group, we observed a three-fold increase in messenger RNA (mRNA) levels of the autophagy regulators LC3B, Atg7, and lysosome-associated membrane protein-2 (LAMP-2) compared to controls. Changes in mRNA levels of FoxO3A and its targets MuRF1, MAFBx, and BNIP3 were on average seven-fold higher in the intervention group compared to controls, but these differences were not statistically significant. Tumor necrosis factor-α (TNF-α) mRNA levels were elevated after the intervention, but we did not detect significant changes in the downstream apoptosis markers caspase 8 and 3. Mitochondrial biogenesis markers (PGC1α and TFAm) were increased by the intervention, but this was not accompanied by significant changes in mitochondrial complex content and activity. In conclusion, although exploratory in nature, this study is among the first to report the stimulation of cellular quality control mechanisms elicited by a weight loss and exercise program in older obese women.
PMCID: PMC3136739  PMID: 21631380
5.  Reduced-Calorie Dietary Weight Loss, Exercise, and Sex Hormones in Postmenopausal Women: Randomized Controlled Trial 
Journal of Clinical Oncology  2012;30(19):2314-2326.
Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women.
Patients and Methods
We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m2, exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet (“diet”; n = 118), (2) moderate- to vigorous-intensity aerobic exercise (“exercise”; n = 117), (3) combined reduced-calorie weight loss diet and moderate- to vigorous-intensity aerobic exercise (“diet + exercise”; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone–binding globulin (SHBG) concentrations (secondary).
Mean age and body mass index were 58 years and 30.9 kg/m2, respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG.
Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.
PMCID: PMC3675691  PMID: 22614972
6.  Impact of Weight Loss on Physical Function with Changes in Strength, Muscle Mass, and Muscle Fat Infiltration in Overweight to Moderately Obese Older Adults: A Randomized Clinical Trial 
Journal of Obesity  2010;2011:516576.
Purpose. Evaluate the effects of weight loss on muscle mass and area, muscle fat infiltration, strength, and their association with physical function. Methods. Thirty-six overweight to moderately obese, sedentary older adults were randomized into either a physical activity plus weight loss (PA+WL) or physical activity plus successful aging health education (PA+SA) program. Measurements included body composition by dual-energy X-ray absorptiometry, computerized tomography, knee extensor strength, and short physical performance battery (SPPB). Results. At 6 months, PA+WL lost greater thigh fat and muscle area compared to PA+SA. PA+WL lost 12.4% strength; PA+SA lost 1.0%. Muscle fat infiltration decreased significantly in PA+WL and PA+SA. Thigh fat area decreased 6-fold in comparison to lean area in PA+WL. Change in total SPPB score was strongly inversely correlated with change in fat but not with change in lean or strength. Conclusion. Weight loss resulted in additional improvements in function over exercise alone, primarily due to loss of body fat.
PMCID: PMC2952914  PMID: 20953373
7.  The influence of exercise and BMI on injuries and illnesses in overweight and obese individuals: a randomized control trial 
Medically treated injuries have been shown to increase with increasing body mass index (BMI). Information is lacking on the frequency and type of injuries and illnesses among overweight and obese adults who engage in regular physical activities as part of weight loss or weight gain prevention programs.
Sedentary adults with BMIs between 25 and 40 kg/m2 (n = 397) enrolled in one of two randomized clinical trials that emphasized exercise as part of a weight loss or weight gain prevention program. Interventions differed by duration of the exercise goal (150, 200, or 300 minutes/week or control group). Walking was prescribed as the primary mode of exercise. At six month intervals, participants were asked, "During the past six months, did you have any injury or illness that affected your ability to exercise?" Longitudinal models were used to assess the effects of exercise and BMI on the pattern of injuries/illnesses attributed to exercise over time; censored linear regression was used to identify predictors of time to first injury/illness attributed to exercise.
During the 18-month study, 46% reported at least one injury/illness, and 32% reported at least one injury that was attributed to exercise. Lower-body musculoskeletal injuries (21%) were the most commonly reported injury followed by cold/flu/respiratory infections (18%) and back pain/injury (10%). Knee injuries comprised one-third of the lower-body musculoskeletal injuries. Only 7% of the injuries were attributed to exercise alone, and 59% of the injuries did not involve exercise. BMI (p ≤ 0.01) but not exercise (p ≥ 0.41) was significantly associated with time to first injury and injuries over time. Participants with higher BMIs were injured earlier or had increased odds of injury over time than participants with lower BMIs. Due to the linear dose-response relationship between BMI and injury/illness, any weight loss and reduction in BMI was associated with a decrease risk of injury/illness and delay in time to injury/illness.
Overweight and obese adults who were prescribed exercise as part of weight loss or weight gain prevention intervention were not at increased risk of injury compared to overweight adults randomized not to participate in prescribed exercise. Since onset of injury/illness and pattern of injuries over time in overweight and obese individuals were attributed to BMI, weight reduction may be an avenue to reduce the risk of injury/illness in sedentary and previously sedentary overweight and obese adults.
Trial Registration NCT00177502 and NCT00177476
PMCID: PMC2818622  PMID: 20145731
8.  Exercise training in obese older adults prevents increase in bone turnover and attenuates decrease in hip BMD induced by weight loss despite decline in bone-active hormones* 
Weight-loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight-loss therapy should include an intervention to minimize bone loss such as exercise training (ET). The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 yrs) obese (BMI ≥30 kg/m2) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (−9.6%) and diet-exercise (−9.4%) groups, not in the exercise (−1%) and control (−0.2%) groups (between-group P<.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (−1.1%) than in the diet group (−2.6%), whereas BMD increased in the exercise group (1.5%) (between-group P<.001) Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%) while they decreased in the exercise group (−13% and −15%) (between-group P<.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (−15%) compared with the diet group (9%) (P=.04). Serum leptin and estradiol concentrations decreased in the diet (−25% and −15%) and diet-exercise (−38% and −13%) groups, not in the exercise and control groups (between-group P=.001). Multivariate analyses revealed that changes in lean body mass (β=.33), serum osteocalcin (β= −.24), and 1-RM strength (β=.23) were independent predictors of changes in hip BMD (all P<.05). In conclusion, the addition of ET to weight-loss therapy among obese older adults prevents weight-loss-induced increase in bone turnover and attenuates weight-loss-induced reduction in hip BMD despite weight-loss-induced decrease in bone-active hormones.
PMCID: PMC3206995  PMID: 21786319
9.  Effects of circuit-based exercise programs on the body composition of elderly obese women 
The aim of this study was to investigate the impact of circuit-based exercise on the body composition in obese older women by focusing on physical exercise and body weight (BW) gain control in older people.
Seventy older women (>60 years old) voluntarily took part in the study. Participants were randomized into six different groups according to body mass index (BMI): appropriate weight (AW) control (AWC) and trained (AWT) groups, overweight (OW) control (OWC) and trained (OWT) groups, and obesity (O) control (OC) and trained (OT) groups. The exercise program consisted of 50 minutes of exercise three times per week for 12 weeks. The exercises were alternated between upper and lower body using rest between sets for 40 seconds with intensity controlled by heart rate (70% of work). The contraction time established was 5 seconds to eccentric and concentric muscular action phase. The following anthropometric parameters were evaluated: height (m), body weight (BW, kg), body fat (BF, %), fat mass (FM, kg), lean mass (LM, kg), and BMI (kg/m2).
The values (mean ± standard deviation [SD]) of relative changes to BW (−8.0% ± 0.8%), BF (−21.4% ± 2.1%), LM (3.0% ± 0.3%), and FM (−31.2% ± 3.0%) to the OT group were higher (P < 0.05) than in the AWT (BW: −2.0% ± 1.1%; BF: −4.6% ± 1.8%; FM: −7.0% ± 2.8%; LM: 0.2% ± 1.1%) and OWT (BW: −4.5% ± 1.0%; BF: −11.0% ± 2.2%; FM: −16.1% ± 3.2%; LM: −0.2% ± 1.0%) groups; additionally, no differences were found for C groups. While reduction (P < 0.03) in BMI according to absolute values was observed for all trained groups (AWT: 22 ± 1 versus 21 ± 1; OWT: 27 ± 1 versus 25 ± 1, OT: 34 ± 1 versus 30 ± 1) after training, no differences were found for C groups.
In summary, circuit-based exercise is an effective method for promoting reduction in anthropometrics parameters in obese older women.
PMCID: PMC3526879  PMID: 23271901
anthropometric parameters; body fat; obesity; older women; physical exercise
10.  Moderate Exercise Attenuates the Loss of Skeletal Muscle Mass That Occurs With Intentional Caloric Restriction–Induced Weight Loss in Older, Overweight to Obese Adults 
Aging is associated with a loss of muscle mass and increased body fat. The effects of diet-induced weight loss on muscle mass in older adults are not clear.
This study examined the effects of diet-induced weight loss, alone and in combination with moderate aerobic exercise, on skeletal muscle mass in older adults.
Twenty-nine overweight to obese (body mass index = 31.8 ± 3.3 kg/m2) older (67.2 ± 4.2 years) men (n = 13) and women (n = 16) completed a 4-month intervention consisting of diet-induced weight loss alone (WL; n = 11) or with exercise (WL/EX; n = 18). The WL intervention consisted of a low-fat, 500–1,000 kcal/d caloric restriction. The WL/EX intervention included the WL intervention with the addition of aerobic exercise, moderate-intensity walking, three to five times per week for 35–45 minutes per session. Whole-body dual-energy x-ray absorptiometry, thigh computed tomography (CT), and percutaneous muscle biopsy were performed to assess changes in skeletal muscle mass at the whole-body, regional, and cellular level, respectively.
Mixed analysis of variance demonstrated that both groups had similar decreases in bodyweight (WL, −9.2% ± 1.0%; WL/EX, −9.1% ± 1.0%) and whole-body fat mass (WL, −16.5%, WL/EX, −20.7%). However, whole-body fat-free mass decreased significantly (p < .05) in WL (−4.3% ± 1.2%) but not in WL/EX (−1.1% ± 1.0%). Thigh muscle cross-sectional area by CT decreased in both groups (WL, −5.2% ± 1.1%; WL/EX, −3.0% ± 1.0%) and was not statistically different between groups. Type I muscle fiber area decreased in WL (−19.2% ± 7.9%, p = .01) but remained unchanged in WL/EX (3.4% ± 7.5%). Similar patterns were observed in type II fibers (WL, −16.6% ± 4.0%; WL/EX, −0.2% ± 6.5%).
Diet-induced weight loss significantly decreased muscle mass in older adults. However, the addition of moderate aerobic exercise to intentional weight loss attenuated the loss of muscle mass.
PMCID: PMC2800807  PMID: 19276190
Weight loss; Aerobic exercise; Obese; Muscle
11.  Weight Loss and Psychologic Gain in Obese Women—Participants in a Supported Exercise Intervention 
The Permanente Journal  2008;12(3):36-45.
Background: Physical activity is a predictor of maintained weight loss; however, causal mechanisms are unclear. Behavioral theories suggest that associated psychologic changes may indirectly affect weight loss.
Objective: We sought to test the association of a behaviorally based exercise support protocol (The Coach Approach [CA]), with and without a group-based nutrition education program (Cultivating Health), with adherence to exercise and changes in physiologic and psychologic factors, and to assess theory-based paths to weight and body-fat changes.
Setting: The study took place in YMCA wellness centers.
Study subjects: Study participation was open to formerly sedentary obese women.
Design: Study participants were randomly assigned to the CA Only (CA; n = 81), The CA Plus Cultivating Health (CA/CH; n = 128), or the control (n = 64) group. We contrasted dropout and attendance rates and changes in self-efficacy (SE), physical self-concept (PSC), total mood disturbance (TMD), body areas satisfaction (BAS), and select physiologic factors during a six-month period. We also analyzed proposed paths to weight loss.
Results: The CA and CA/CH groups had significantly lower exercise dropout rates (χ2 = 44.67, p < 0.001) and higher attendance rates (F = 10.02; p < 0.001) than the control group did. Improvements in body fat, body mass index (BMI), and waist circumference were significant for only the CA and CA/CH groups. Significant improvements in TMD, PSC, and BAS scores were found for all groups, with effect sizes greater in the groups incorporating the CA protocol. Within the five paths assessed, entry of changes in TMD and BAS scores into multiple-regression equations, along with SE and PSC scores, increased the explained variance in exercise session attendance from 5% (p = 0.01) to 16% (p < 0.001). Exercise session attendance was significantly associated with changes in body fat (r = −0.41; p < 0.001) and BMI (r = −0.46; p < 0.001).
Conclusion: Counseling based on social cognitive and self-efficacy theory may increase exercise adherence and improve variables indirectly related to weight and body-fat reductions. Although decreases in body fat and BMI were obtained, they appeared less pronounced than psychologic improvements. Additional research on interrelations of physical activity, psychologic factors, and weight change is warranted for development of obesity treatments.
PMCID: PMC3037122  PMID: 21331208
12.  The Effect of Randomization to Weight Loss on Total Mortality in Older Overweight and Obese Adults: The ADAPT Study 
Although weight loss reduces risk for comorbid diseases, many observational studies suggest that weight loss is associated with increased mortality risk, leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults. However, whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction. Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used to determine whether randomization to a weight reduction program was associated with total mortality in overweight/obese older adults.
ADAPT (n = 318; mean age 69 ± 6 years, body mass index 34 ± 5 kg/m2, 72% female) assessed the influence of weight loss (achieved through dietary counseling and lifestyle modification) and/or exercise on function in overweight/obese older adults with knee osteoarthritis. ADAPT ended in December 1999. Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes.
The mortality rate for those randomized to the 18-month weight loss intervention (n = 159, mean weight loss = −4.8 kg, 15 deaths) was lower than that for those not randomized to the weight loss intervention (n = 159, mean weight loss = −1.4 kg, 30 deaths; hazard rate ratio = 0.5, 95% confidence interval 0.3–1.0). Results were not appreciably changed when analyses were stratified by age, gender, baseline weight status, or magnitude of weight loss.
In older adults, intentional weight loss was not associated with increased total mortality and may reduce mortality risk. Observational studies of weight loss, especially when intentionality cannot be rigorously established, may be misleading with respect to the effect of weight loss on mortality.
PMCID: PMC3107029  PMID: 20080875
Intentional weight loss; Mortality; Aging; Obesity
13.  Aerobic exercise alone results in clinically significant weight loss for men and women: Midwest Exercise Trial-2 
Obesity (Silver Spring, Md.)  2013;21(3):E219-E228.
Exercise is recommended by public health agencies for weight management; however, the role of exercise is generally considered secondary to energy restriction. Few studies exist that have verified completion of exercise, measured the energy expenditure of exercise, and prescribed exercise with equivalent energy expenditure across individuals and genders.
The objective of this study was to evaluate aerobic exercise, without energy restriction, on weight loss in sedentary overweight and obese men and women.
Design and Methods
This investigation was a randomized, controlled, efficacy trial in 141 overweight and obese participants (body mass index, 31.0 ± 4.6 kg/m2; age 22.6 ± 3.9 years). Participants were randomized (2:2:1 ratio) to exercise at either 400 kcal/session or 600 kcal/session or to a non-exercise control. Exercise was supervised, 5 days/week, for 10 months. All participants were instructed to maintain usual ad libitum diets. Due to the efficacy design, completion of ≥ 90% of exercise sessions was an a priori definition of per protocol, and these participants were included in the analysis.
Weight loss from baseline to 10 months for the 400 and 600 kcal/session groups was 3.9 ± 4.9kg (4.3%) and 5.2 ± 5.6kg (5.7%), respectively compared to weight gain for controls of 0.5 ± 3.5kg (0.5%) (p<0.05). Differences for weight loss from baseline to 10 months between the exercise groups and differences between men and women within groups were not statistically significant.
Supervised exercise, with equivalent energy expenditure, results in clinically significant weight loss with no significant difference between men and women.
PMCID: PMC3630467  PMID: 23592678
14.  Addition of Aerobic Exercise to a Weight Loss Program Increases BMD, with an Associated Reduction in Inflammation in Overweight Postmenopausal Women 
Calcified tissue international  2009;84(4):257-265.
Increased inflammation and weight loss are associated with a reduction in bone mineral density (BMD). Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines. We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers, thus mediating changes in BMD. This was a nonrandomized controlled trial. Eighty-six overweight and obese postmenopausal women (50–70 years of age; BMI, 25–40 kg/m2) participated in a weight loss (WL; n = 40) or weight loss plus walking (WL + AEX; n = 46) program. Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry, interleukin-6, tumor necrosis factor-α, soluble receptors of IL-6, and TNF-α (sTNFR1 and sTNFR2; receptors in a subset of the population), VO2 max, fat mass, and lean mass. Weight decreased in the WL (p < 0.001) and WL + AEX (p < 0.001) groups. VO2 max increased (p < 0.001) after WL + AEX. There was a 2% increase in femoral neck BMD in the WL + AEX group (p = 0.001), which was significantly different from the WL group. The change in sTNFR1 was significantly associated with the change in femoral neck BMD (p < 0.05). The change in VO2 max was an independent predictor of the change in femoral neck BMD. Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women.
PMCID: PMC2926800  PMID: 19280097
Aging; Cytokines; Inflammation; Exercise; Weight loss
15.  Moderators and Mediators of Exercise-Induced Objective Sleep Improvements in Midlife and Older Adults with Sleep Complaints 
Regular exercise can improve sleep quality, but for whom and by what means this occurs remain unclear. We examined moderators and mediators of objective sleep improvements in a 12-month randomized controlled trial among initially underactive midlife and older adults reporting mild/moderate sleep complaints. Participants (N=66, 67% women, 55–79 years) were randomized to moderate-intensity exercise or health education control. Putative moderators were gender, age, and baseline physical function, self-reported global sleep quality, and physical activity levels. Putative mediators were changes in BMI, depressive symptoms, and physical function at 6 months. Objective sleep outcomes measured by in-home PSG were percent time in Stage 1 sleep, percent time in Stage 2 sleep, and number of awakenings during the first third of sleep at 12 months. Baseline physical function and sleep quality moderated changes in Stage 1 sleep; individuals with higher initial physical function (p=0.01) and poorer sleep quality (p=0.03) had greater improvements. Baseline physical activity level moderated changes in Stage 2 sleep (p=0.04) and number of awakenings (p=0.01); more sedentary individuals had greater improvements. Decreased depressive symptoms (CI:−1.57 to −0.02) mediated change in Stage 1 sleep. Decreased depressive symptoms (CI: −0.75 to −0.01), decreased BMI (CI:−1.08 to −0.06), and increased physical function (CI:0.01 to 0.72) mediated change in number of awakenings. In conclusion, initially less active individuals with higher initial physical function and poorer sleep quality improved the most. Affective, functional, and metabolic mediators specific to different parameters of sleep architecture were suggested. Collectively, the results indicate strategies to more efficiently treat poor sleep through exercise in older adults.
PMCID: PMC3210555  PMID: 21688915
objective sleep; exercise; physical activity; multiple mediation; moderation
16.  Randomized controlled trial of a comprehensive home environment-focused weight loss program for adults 
Behavioral weight loss programs (BWL) provide limited instruction on how to change the environmental context of weight-regulating behaviors, perhaps contributing to regain. Drawing on social ecological models, this trial evaluated a comprehensive weight loss program that targeted both an individual’s behavior and their physical and social home environment.
Overweight and obese adults (N=201; 48.9±10.5 years; 78.1% women) were randomized to BWL or to BWL plus home environment changes (BWL+H). Groups met weekly for 6 months and bi-monthly for 12 months. BWL+H participants were given items to facilitate healthy choices in their homes (e.g., exercise equipment, portion plates) and attended treatment with a household partner. Weight loss at 6 and 18 months was the primary outcome.
BWL+H changed many aspects of the home environment and produced better 6 month weight losses than BWL (p=.017). At 18 months, no weight loss differences were observed (p=.19) and rates of regain were equivalent (p=.30). Treatment response was moderated by gender (6 month p=.01; 18 month p=.006). Women lost more weight in BWL+H than BWL at 6 and 18 months, whereas men in BWL lost more weight than those in BWL+H at 18 months. Partners, regardless of gender, lost more weight in BWL+H than BWL at both time points (ps<.0001).
The home food and exercise environment is malleable and targeting this microenvironment appears to improve initial weight loss, and in women, 18-month outcomes. Research is needed to understand this gender difference and to develop home-focused strategies with more powerful and sustained weight loss effects.
PMCID: PMC3393797  PMID: 22309885
weight loss; home environment; maintenance
17.  The Effect of Pioglitazone and Resistance Training on Body Composition in Older Men and Women Undergoing Hypocaloric Weight Loss 
Obesity (Silver Spring, Md.)  2011;19(8):1636-1646.
Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65–79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m2) and women (n = 40, BMI = 33.3 ± 4.9 kg/m2) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (−1,160 vs. −647 cm3, P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (−104 vs. −298 cm3, P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: −43 vs. −88 cm3, P = 0.005; women: −34 vs. −59 cm3, P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.
PMCID: PMC3091968  PMID: 21233810
18.  A Behavioral Weight-Loss Intervention in Persons with Serious Mental Illness 
The New England journal of medicine  2013;368(17):1594-1602.
Overweight and obesity are epidemic among persons with serious mental illness, yet weight-loss trials systematically exclude this vulnerable population. Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent. Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness.
We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and randomly assigned them to an intervention or a control group. Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions. Weight change was assessed at 6, 12, and 18 months.
Of 291 participants who underwent randomization, 58.1% had schizophrenia or a schizoaffective disorder, 22.0% had bipolar disorder, and 12.0% had major depression. At baseline, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.3, and the mean weight was 102.7 kg (225.9 lb). Data on weight at 18 months were obtained from 279 participants. Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit. At 18 months, the mean between-group difference in weight (change in intervention group minus change in control group) was −3.2 kg (−7.0 lb, P = 0.002); 37.8% of the participants in the intervention group lost 5% or more of their initial weight, as compared with 22.7% of those in the control group (P = 0.009). There were no significant between-group differences in adverse events.
A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness. Given the epidemic of obesity and weight-related disease among persons with serious mental illness, our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population.
PMCID: PMC3743095  PMID: 23517118
19.  Obesity, Intentional Weight Loss, and Physical Disability in Older Adults 
We examine obesity, intentional weight loss, and physical disability in older adults. Based on prospective epidemiological studies, BMI exhibits a curvilinear relationship with physical disability; there appears to be some protective effect associated with older adults being overweight. Whereas the greatest risk for physical disability occurs in older adults who are ≥class II obesity, the effects of obesity on physical disability appears to be moderated by both sex and race. Obesity at age 30 constitutes a greater risk for disability later in life than when obesity develops at age 50 or later; however, physical activity may buffer the adverse effects obesity has on late life physical disability. Data from a limited number of randomized clinical trials (RCTs) reinforce the important role that physical activity plays in weight loss programs for older adults. Furthermore, short-term studies have found that resistance training may be particularly beneficial in these programs since this mode of exercise attenuates the loss of fat-free mass during caloric restriction. Multi-year RCTs are needed to examine whether weight loss can alter the course of physical disablement in aging and to determine the long-term feasibility and effects of combining resistance exercise with weight loss in older adults.
PMCID: PMC2888667  PMID: 19922431
Body-mass index (BMI); physical function; elderly; physical activity; exercise
20.  The DASH Diet and Insulin Sensitivity 
Current hypertension reports  2011;13(1):67-73.
Lifestyle modifications, including adoption of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, weight loss in individuals who are overweight or obese, and physical activity, are effective in the prevention and treatment of hypertension. A healthy lifestyle may also have beneficial effects on metabolic abnormalities, such as insulin resistance, that are associated with high blood pressure. This review examines the independent and combined effects of the DASH diet and weight loss plus exercise on blood pressure and insulin sensitivity, with a focus on recently published results from the ENCORE study. Our data suggest that the DASH eating plan alone lowers blood pressure in overweight individuals with higher than optimal blood pressure, but significant improvements in insulin sensitivity are observed only when the DASH diet is implemented as part of a more comprehensive lifestyle modification program that includes exercise and weight loss.
PMCID: PMC3767170  PMID: 21058045
Hypertension; Blood pressure; Diabetes; Insulin sensitivity; DASH diet; Exercise; Physical activity; Weight loss; Lifestyle modification
21.  Changes in Eating, Physical Activity, and Related Behaviors in a Primary-Care-Based Weight Loss Intervention 
To examine changes in eating behaviors and physical activity, as well as predictors of weight loss success, in obese adults who participated in a 2-year behavioral weight loss intervention conducted in a primary care setting.
A longitudinal, randomized-controlled, multi-site trial.
390 obese (body mass index, 30 to 50 kg/m2) adults, ≥21 yr, in the Philadelphia region.
Participants were assigned to one of three interventions 1) Usual Care [Quarterly primary care provider (PCP) visits that included education on diet and exercise]; 2) Brief Lifestyle Counseling [quarterly PCP visits plus monthly Lifestyle Counseling (LC) sessions about behavioral weight control]; or 3) Enhanced Brief LC (the previous intervention with a choice of meal replacements or weight loss medication).
At month 24, participants in both Brief LC and Enhanced Brief LC reported significantly greater improvements in mean (±SE) dietary restraint than those in Usual Care (4.4±0.5, 4.8±0.5, and 2.8±0.5, respectively; both ps≤0.016). The percentage of calories from fat, along with fruit and vegetable consumption, did not differ significantly among the three groups. The Brief LC and Enhanced Brief LC groups both reported significantly greater energy expenditure (kcal/week) at month 24 than Usual Care (+593.4±175.9, +415.4±179.6, and −70.4±185.5, respectively; both ps≤0.037). The strongest predictor of weight loss at month 6 (partial R2=33.4%, p<0.0001) and at month 24 (partial R2=19.3%, p<0.001) was food records completed during the first 6 months. Participants who achieved a 5% weight loss at month 6 had 4.7 times greater odds of maintaining a 5% weight loss at month 24.
A behavioral weight loss intervention delivered in a primary care setting can result in significant weight loss, with corresponding improvements in eating restraint and energy expenditure. Moreover, completion of food records, along with weight loss at month 6, is a strong predictor of long-term weight loss.
PMCID: PMC3786775  PMID: 23921776
lifestyle intervention; weight loss; Eating Inventory; food intake; physical activity
22.  Weight loss in obese older adults increases serum sclerostin and impairs hip geometry but both are prevented by exercise training* 
Journal of Bone and Mineral Research  2012;27(5):1215-1221.
We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. One-hundred-seven obese (BMI ≥30 kg/m2) older (≥65 yrs) adults were randomly assigned to control, diet, exercise and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy x-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (−9.6% and −9.4%, respectively), while weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6±1.7% and 10.5±1.9% at 6 and 12 months, respectively, all P<0.05), while they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7±1.6% and 0.4±1.7% at 6 and 12 months, respectively, all P=NS). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (P<0.05). In conclusion, the increase in sclerostin levels with weight loss which was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.
PMCID: PMC3361603  PMID: 22392834
sclerostin; hip geometry; weight loss; exercise; mechanical loading; obesity
23.  Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial 
Cancer Research  2012;72(9):2314-2326.
Obese and sedentary persons have increased risk for cancer; inflammation is a hypothesized mechanism. We examined the effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in 439 women. Overweight and obese postmenopausal women were randomized to 1-year: caloric restriction diet (goal of 10% weight loss, N=118), aerobic exercise (225 minutes/week of moderate-to-vigorous activity, N=117), combined diet+exercise (N=117) or control (N=87). Baseline and 1-year high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), interleukin-6 (IL-6), leukocyte and neutrophil levels were measured by investigators blind to group. Inflammatory biomarker changes were compared using generalized estimating equations. Models were adjusted for baseline body mass index (BMI), race/ethnicity and age. 438 (N=1 in diet+exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, p-value) 0.92mg/L (0.53–1.31, P<0.001) in the diet and 0.87mg/L (0.51–1.23, P<0.0001) in the diet+exercise groups. IL-6 decreased by 0.34pg/ml (0.13–0.55, P=0.001) in the diet and 0.32pg/ml (0.15–0.49, P<0.001) in the diet+exercise groups. Neutrophil counts decreased by 0.31×109/L (0.09–0.54, P=0.006) in the diet and 0.30×109/L (0.09–0.50, P=0.005) in the diet+exercise groups. Diet and diet+exercise participants with ≥5% weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared to controls. The diet and diet+exercise groups reduced hs-CRP in all subgroups of baseline BMI, waist circumference, CRP level, and fasting glucose. Our findings indicate that a caloric restriction weight loss diet with or without exercise reduces biomarkers of inflammation in postmenopausal women, with potential clinical significance for cancer risk reduction.
PMCID: PMC3342840  PMID: 22549948
inflammation; postmenopausal women; obesity; exercise; dietary weight loss
24.  Using pedometers to increase physical activity in overweight and obese women: a pilot study 
BMC Public Health  2009;9:309.
Most public health guidelines recommend that adults participate in 30 minutes of moderate intensity physical activity on most days of the week. Establishing new ways to achieve these targets in sedentary populations need to be explored. This research evaluated whether the daily use of pedometers could increase physical activity and improve health outcomes in sedentary overweight and obese women.
Twenty six overweight and obese middle-aged women were randomized into two groups: The control group was not able to record their steps daily, whilst the pedometer group, were asked to record the number of steps on a daily basis for 12 weeks.
Our data showed that the pedometer group significantly increased their steps/day, by 36%, at the end of the 12 weeks, whereas the control group's physical activity levels remained unchanged. There was no significant difference in weight or body fat composition in the pedometer group compared to the control group. However, there was a significant decrease in systolic blood pressure in the pedometer group (112.8 ± 2.44 mm Hg) compared to the control group (117.3 ± 2.03 mm Hg) (p = 0.003).
In conclusion, this pilot study shows that the combination of having step goals and immediate feedback from using a pedometer was effective in increasing physical activity levels in sedentary overweight and obese women.
Trial registration
PMCID: PMC2741450  PMID: 19703317
25.  Television Viewing Time is Associated with Overweight/Obesity Among Older Adults, Independent of Meeting Physical Activity and Health Guidelines 
Journal of Epidemiology  2012;22(1):50-56.
Previous studies have shown associations of sedentary behavior with cardiovascular risk, independent of moderate-to-vigorous physical activity (MVPA). However, few studies have focused on older adults. This study examined the joint associations of television (TV) viewing time and MVPA with overweight/obesity among Japanese older adults.
A population-based, cross-sectional mail survey was used to collect self-reported height, weight, time spent in TV viewing, and MVPA from 1806 older adults (age: 65–74 years, men: 51.1%). Participants were classified into 4 categories according to TV viewing time (dichotomized into high and low around the median) and MVPA level (dichotomized into sufficient and insufficient by the physical activity guideline level of ≥150 minutes/week). Odds ratios (ORs) for overweight/obesity (body mass index ≥25 kg/m2) were calculated according to the 4 TV/MVPA categories, adjusting for potential confounders.
Of all participants, 20.1% were overweight/obese. The median TV viewing time (25th, 75th percentile) was 840 (420, 1400) minutes/week. As compared with the reference category (high TV/insufficient MVPA), the adjusted ORs (95% CI) of overweight/obesity were 0.93 (0.65, 1.34) for high TV/sufficient MVPA, 0.58 (0.37, 0.90) for low TV/insufficient MVPA, and 0.67 (0.47, 0.97) for low TV/sufficient MVPA.
In this sample of older adults, spending less time watching TV, a predominant sedentary behavior, was associated with lower risk of being overweight or obese, independent of meeting physical activity guidelines. Further studies using prospective and/or intervention designs are warranted to confirm the presently observed effects of sedentary behavior, independent of physical activity, on the health of older adults.
PMCID: PMC3798580  PMID: 22156288
sedentary behavior; cardiovascular risk factor; obesity

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