Effect of Baseline BMI and IL-6 Subgroup Membership on Gait Speed Response to Caloric Restriction in Older Adults with Obesity.

BACKGROUND: Prior work shows caloric restriction (CR) can improve physical function among older adults living with obesity. However, the contribution of starting weight and inflammatory burden to CR-associated functional improvements is unclear. The primary purpose of this study was to determine if CR-associated gait speed change varied by body mass index (BMI) and plasma interleukin 6 (IL-6) at baseline and secondarily to determine the contribution of BMI change and IL-6 change to gait speed change. DESIGN, SETTING, PARTICIPANTS: Data from eight randomized control trials were pooled, with 1184 participants randomized to CR (n=661) and No CR (n=523) conditions. All studies assessed outcomes before and five or six months after assignment to CR or No CR. MEASUREMENTS: BMI and IL-6 were assessed at baseline using standard procedures. Gait speed was assessed with the six-minute walk test or 400m walk test. Baseline BMI/IL-6 subgroups were constructed using BMI≥35 kg/m2 and IL-6>2.5 pg/mL thresholds. Participants with BMI≥35 kg/m2 were grouped into class 2+ obesity and BMI<35 kg/m2 into class 1- obesity; IL-6>2.5 pg/mL were grouped into high IL-6, and <2.5 pg/mL as low IL-6 (class 2+ obesity/high IL-6: n=288, class 2+ obesity/low IL-6: n=143, class 1- obesity/high IL-6: n=354, or class 1- obesity/low IL-6: n=399). All analyses used adjusted general linear models. RESULTS: Gait speed significantly improved with CR versus non-CR [mean difference: +0.02 m/s (95% CI: 0.01, 0.04)]. CR assignment significantly interacted with BMI/IL-6 subgroup membership (p=0.03). Greatest gait speed improvement was observed in the class 2+ obesity/high IL-6 subgroup [+0.07 m/s (0.03, 0.10)]. No other subgroups observed significant gait speed change. For each unit decrease in BMI, gait speed change increased by +0.02 m/s (p<0.001; R2=0.26), while log IL-6 change did not significantly affect gait speed change [+0.01 m/s (p=0.20)]. CONCLUSIONS: Only the class 2+ obesity/high IL-6 subgroup significantly improved gait speed in response to CR. Improvement in gait speed in this subgroup was driven by a larger decrease in BMI, but not IL-6, in response to CR. Individuals with class 2+ obesity and high IL-6 are most likely to show improved gait speed in response to CR, with improvement predominantly driven by reductions in BMI.

The Effects of a Pain Management-Focused Mobile Health Behavior Intervention on Older Adults' Self-efficacy, Satisfaction with Functioning, and Quality of Life: a Randomized Pilot Trial.

BACKGROUND: This report investigates the impact of a remote physical activity intervention on self-efficacy, satisfaction with functioning, and health-related quality of life (HRQOL) as assessed by the SF-36 in obese older adults with chronic pain. The intervention was group-mediated in nature and based in social cognitive theory and mindfulness-based relapse prevention. METHODS: Participants (N = 28; 70.21 ± 5.22 years) were randomly assigned to receive either the active intervention, which focused on reducing caloric intake and increasing steps across the day or to a waitlist control condition. RESULTS: Over 12 weeks, intervention participants reported a moderate, positive improvement in self-efficacy for walking relative to control. They also reported large magnitude improvements in satisfaction for physical functioning as well as improvements on pain and the physical functioning subscales of the SF-36. CONCLUSIONS: These findings expand on previous research showing similar effects in response to structured exercise, this time via a protocol that is likely to be scalable and sustainable for many older adults. Additional work on larger and more diverse samples is warranted.

Implementation of a Community Walking Program (Walk On!) for Functionally-Limited Older Adults.

BACKGROUND: Walking interventions improve physical function, reduce fall risk, and prevent mobility disability-even in those with compromised walking ability. However, most prior studies have been conducted in controlled research settings, with no dissemination of an evidence-based walking program for older adults who have mobility limitations and/or are socially isolated. OBJECTIVES: This study reports data on the feasibility and acceptability of a community-based walking program (Walk On!) for older adults who are functionally limited, and assesses changes in physical function among attendees. The program sessions focused on long-distance walking, and took place for one-hour, for two days/week, and for 12 weeks at a time. DESIGN: Pilot implementation study. SETTING: Local church in Winston-Salem, NC. PARTICIPANTS: 49 program participants; Measurements: Physical function battery and satisfaction survey data, as well as formative evaluation data from six attendees of a focus group, are reported. RESULTS: The majority of the participants were >75 years (71%), female (65%), and presented with low levels of physical function (usual gait speed=0.79±0.16; 30.6% used an assistive device). Satisfaction with the program was high (100% would recommend it to others) and focus group results were overwhelmingly positive. Mean attendance to scheduled sessions was 77%±21%, and 63% of participants attended at least 75% of scheduled sessions (n=8 attended 100%). On average, participants improved their 6-min walk distance by 8.9%, their SPPB score by 15.4%, their timed-up-go time by 9.0%, and their usual gait speed by 11.4%. CONCLUSION: The results of the initial evaluation of Walk On! show high feasibility and acceptability of the program, as well as efficacy for improving physical function. Further research is needed to evaluate a delivery method for wider implementation of the program and to definitively test its effectiveness for improving function and other health benefits.

Inflammatory cytokines mediate the effects of diet and exercise on pain and function in knee osteoarthritis independent of BMI.

OBJECTIVE: Diet restriction and exercise form key treatments for osteoarthritis (OA) related symptoms in overweight and obese individuals. Although both interventions are known to influence systemic low-grade inflammation, which is related to pain levels and functional limitations, little is known about the potential changes in systemic inflammation as a working mechanism of diet restriction and exercise in knee OA. DESIGN: Data from the Arthritis, Diet, and Activity Promotion Trial (ADAPT) were used. Through causal mediation analyses, the proportion of the effect of a 18 months diet and exercise intervention explained by the 18 months change in interleukin (IL)-6, TNF-α, soluble IL-6 receptor, soluble IL-1 receptor, CRP, and BMI were assessed, using self-reported pain and function as outcomes. RESULTS: The change in inflammatory factors accounted for 15% of the total effect on pain and was totally independent of the change in BMI. The change in inflammatory factors accounted for 29% of the effect on function, with the change in BMI adding only 4% to the total mediated effect. CONCLUSIONS: The change in inflammatory factors after the diet and exercise intervention was a 'medium' size mediator of the effect on pain and a 'strong' mediator for the effect on function in overweight and obese individuals with knee OA. The change in BMI added minimally to the mediated effect on function. These results highlight the relevance of changes in systemic inflammation as drivers for clinically relevant effects after diet and exercise in overweight and obese individuals with knee OA.

Feasibility of Weighted Vest Use during a Dietary Weight Loss Intervention and Effects on Body Composition and Physical Function in Older Adults.

BACKGROUND: While intentional weight loss in older adults with obesity yields clinically important health benefits there is a need to minimize the negative effects of weight loss on concomitant loss of muscle mass and strength. Data show wearing weighted vests during exercise improves lean mass and lower extremity strength, however the efficacy of wearing a weighted vest during a period of weight loss to mitigate muscle and strength loss is not known. OBJECTIVES: This study examined the feasibility of daily weighted vest use during a dietary weight loss intervention, and examined effects of vest use on body composition and physical function in well-functioning older adults with obesity. DESIGN: Randomized, controlled pilot study. SETTING: Wake Forest Baptist Medical Center in Winston-Salem, NC. PARTICIPANTS: 37 older (age=65-79 yrs), obese (BMI=30-40 kg/ m2) sedentary men and women. INTERVENTIONS: 22-week behavioral diet intervention (targeting 10% weight loss, 1100-1300 kcals/day) with (Diet+Vest; n=20) or without (Diet; n=17) weighted vest use (goal of 10 hours/ day with weight added weekly according to individual loss of body mass). MEASUREMENTS: Body composition by dual-energy x-ray absorptiometry and measures of physical function, mobility, and muscle strength/power. RESULTS: Average weighted vest use was 6.7±2.2 hours/day and the vest-wear goal of 10 hrs/day was achieved for 67±22% of total intervention days. Five participants reported adverse events from wearing the vest (all back pain or soreness). Both groups lost a similar amount of weight (Diet= -11.2±4.4 kg; Diet+Vest = -11.0±6.3 kg; p<0.001), with no differences between groups (p=0.25). Fat mass, lean mass, and % body fat decreased significantly (p<0.0001), with no differences between groups. Compared to Diet+Vest, the Diet intervention resulted in greater decreases in leg power (p<0.02), with no other between group differences in physical function. CONCLUSION: This pilot study showed that vest use during dietary weight loss is feasible and safe in well-functioning older adults with obesity. Larger studies are needed to definitively determine whether external replacement of lost weight during caloric restriction may preserve lower extremity muscle strength and power.

Empowered with Movement to Prevent Obesity & Weight Regain (EMPOWER): Design and methods.

Promoting lasting weight loss among older adults is an important public health challenge. Participation in physical activity aids in weight loss and is important for the maintenance of physical function and quality of life. However, traditional intensive lifestyle interventions place a focus on discrete bouts of structured activity, leaving much of the remainder of the day for sedentary behavior. Structured exercise and weight loss programs often produce short-term weight loss that is typically followed by weight regain, and older adults are more likely to regain weight as fat mass rather than lean mass. Preliminary evidence suggests a focus on day-long movement intended to minimize time spent sitting produces better short-term weight loss and weight maintenance. Herein we describe the design and methods for a three-arm randomized controlled trial comparing mHealth-supported weight loss (WL) + structured exercise (EX); WL + a novel daily movement intervention (SitLess); and WL + EX + SitLess. Older adults (N = 180) will be randomly assigned to one of the three interventions, each comprised of a 6-month intensive phase; a 3-month transition phase; and a 9-month maintenance phase. The primary aim of the study is to determine whether the addition of SitLess to a traditional intensive lifestyle intervention comprised of dietary weight loss and structured exercise produces a larger 18-month reduction in body weight relative to WL + EX and WL + SitLess.

Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA).

OBJECTIVE: To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA). DESIGN: Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA) trial randomized to either an 18 month exercise control group (E), weight loss diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6) were quantitated using ELISAs. Radiographic progression was defined as a decrease in joint space width of ≥0.7 mm. Statistical modeling of group means and associations used mixed models adjusted for visit, baseline body mass index (BMI), gender, and baseline values of the outcome. RESULTS: Compared to the E control group, C1M was significantly lower in the D and D + E groups at both 6 and 18 months while C3M was significantly lower in D and D + E at 6 months and in D + E at 18 months. C2M did not change in any group. Using data from all groups, change in C1M (P < 0.0001), C3M (P < 0.0001), as well as CRPM (P = 0.0004) from baseline to 18 months was positively associated with change in weight. No marker was associated with change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or radiographic progression. C3M (P = 0.008) and CRPM (P = 0.028) were positively associated with change in WOMAC function. Change in IL-6 was positively associated with change in C1M, C3M, and CRPM. CONCLUSION: Overweight and obese adults with knee OA who lost weight from diet and diet plus exercise reduced serum markers of interstitial matrix turnover and inflammation but not type II collagen degradation.

Legacy effects of short-term intentional weight loss on total body and thigh composition in overweight and obese older adults.

OBJECTIVE: Weight regain following intentional weight loss may negatively impact body composition, accelerating fat regain and increasing risk of physical disability. The purpose of this study was to compare long-term changes in whole body and thigh composition in obese older adults who intentionally lost and then partially regained weight to obese older adults who remained weight stable. SUBJECTS/METHODS: This pilot study analyzed total body (dual-energy X-ray absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data collected from 24 older (65-79 years) adults 18 months after completion of a 5-month randomized trial that compared resistance training alone (RT) with RT plus caloric restriction (RT+CR). RESULTS: Mean loss of body mass in the RT+CR group (n=13) was 7.1±2.4 kg during the 5-month intervention (74% fat mass; 26% lean mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.3±1.8 kg; P=0.64). Differential group effects were observed for all DXA and CT body composition measures at 5 months (all P⩽0.01); however, by 23 months, group differences persisted only for total body (RT+CR: 81.6±10.0 kg vs RT: 88.5±14.9 kg; P=0.03) and lean (RT+CR: 50.8±9.3 kg vs RT: 54.4±12.0 kg; P<0.01) mass. All RT+CR participants regained weight from 5 to 23 months (mean gain=+4.8±2.6 kg; P<0.01). Total fat mass and all thigh fat volumes increased, whereas thigh muscle volume decreased, during the postintervention follow-up in RT+CR (all P⩽0.01). In the RT group, body mass did not change from 5 to 23 months (-0.2±0.9 kg; P=0.87). Decreased total thigh volume, driven by the loss of thigh muscle volume, were the only postintervention body composition changes observed in the RT group (both P<0.04). CONCLUSIONS: Short-term body composition benefits of an RT+CR intervention may be lost within 18 months after completion of the intervention.

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study.

INTRODUCTION: Metabolic factors may contribute to osteoarthritis (OA). This study employed metabolomics analyses to determine if differences in metabolite profiles could distinguish people with knee OA who exhibited radiographic progression. METHODS: Urine samples obtained at baseline and 18 months from overweight and obese adults in the Intensive Diet and Exercise for Arthritis (IDEA) trial were selected from two subgroups (n = 22 each) for metabolomics analysis: a group that exhibited radiographic progression (≥0.7 mm decrease in joint space width, JSW) and an age, gender, and body mass index (BMI) matched group who did not progress (≤0.35 mm decrease in JSW). Multivariate analysis methods, including orthogonal partial least square discriminate analysis, were used to identify metabolite profiles that separated progressors and non-progressors. Plasma levels of IL-6 and C-reactive protein (CRP) were evaluated as inflammatory markers. RESULTS: Multivariate analysis of the binned metabolomics data distinguished progressors from non-progressors. Library matching revealed that glycolate, hippurate, and trigonelline were among the important metabolites for distinguishing progressors from non-progressors at baseline whereas alanine, N,N-dimethylglycine, glycolate, hippurate, histidine, and trigonelline, were among the metabolites that were important for the discrimination at 18 months. In non-progressors, IL-6 decreased from baseline to 18 months while IL-6 was unchanged in progressors; the change over time in IL-6 was significantly different between groups. CONCLUSION: These findings support a role for metabolic factors in the progression of knee OA and suggest that measurement of metabolites could be useful to predict progression. Further investigation in a larger sample that would include targeted investigation of specific metabolites is warranted.

The Intensive Diet and Exercise for Arthritis (IDEA) trial: 18-month radiographic and MRI outcomes.

PURPOSE: Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA). METHODS: Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27-41 kg m(-2)) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender. RESULTS: Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D -0.07 (SE 0.22) mm, D + E -0.27 (SE 0.22) mm and E -0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D -0.10(0.05) mm, D + E -0.13(0.04) mm and E -0.05(0.04) mm (P = 0.42). CONCLUSION: Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.

Effect of protein source during weight loss on body composition, cardiometabolic risk and physical performance in abdominally obese, older adults: a pilot feeding study.

OBJECTIVES: The purpose of this pilot study was to begin to examine the effect of dietary protein source (soy protein versus non-soy protein) during weight loss on body composition, and cardiometabolic and functional decline risk factors in older, abdominally obese adults. DESIGN: Two-arm, single-blind, randomized, controlled trial. SETTING: Wake Forest School of Medicine, Winston-Salem NC 27157, USA. PARTICIPANTS: 25 older (68.4±5.5 years, 88% female), abdominally obese (BMI: 35.1±4.3 kg/m2; WC: 101.4±13.1 cm) men and women were randomized to participate in the study. INTERVENTION: A 12-week weight loss intervention, with participants randomized to consume soy protein-based meal replacements (S; n=12) or non-soy protein-based meal replacements (NS; n=12), in addition to prepared meals, and all participants targeted to receive an individualized caloric deficit of 500 kcal/day. MEASUREMENTS: Body weight and composition (assessed via DXA and CT), conventional biomarkers of cardiometabolic risk, and physical performance measures were assessed pre- and post-intervention. Additional endpoints of feasibility (accrual, participation, retention, compliance, and safety) are reported. RESULTS: A total of 24 participants (87% female) completed the study (96% retention) and lost an average of 7.8±3.0 kg over the 12-week period, with no difference seen between groups (p=0.83). Although nearly all measures of global and regional body composition were significantly reduced following the 12-week intervention, differences were not observed between groups. Among cardiometabolic risk factors and physical performance measures, only diastolic blood pressure was significantly lower in the NS group compared to the S group (66.7±2.7 mmHg vs 73.5±2.7 mmHg, respectively; p=0.04). Interestingly, in groups combined, despite significant reductions in body weight and lean mass, no significant changes in 400-meter walk time (+5.3±43.4 s), short physical performance battery score (+0.1±1.0), grip strength (-0.3±3.2 kg), or relative knee extensor strength (-0.0±0.0 N/m/cm3 thigh muscle volume) were observed. CONCLUSIONS: Data presented here suggest that a 12-week weight loss intervention, which incorporates S and NS meal replacement products, is associated with clinically significant weight loss and improvements in several parameters of cardiometabolic risk and unchanged physical function and strength. RESULTS do not differ by protein source and suggest that soy protein is at least as good as other protein sources for weight loss during low-calorie dietary interventions in older adults.

Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis.

OBJECTIVE: To describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss. DESIGN: Data come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models. RESULTS: Intentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (ß = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (ß = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss. CONCLUSIONS: Achievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

The independent and combined effects of intensive weight loss and exercise training on bone mineral density in overweight and obese older adults with osteoarthritis.

OBJECTIVE: To determine the effects of dietary-induced weight loss (D) and weight loss plus exercise (D + E) compared to exercise alone (E) on bone mineral density (BMD) in older adults with knee osteoarthritis (OA). DESIGN: Data come from 284 older (66.0 ± 6.2 years), overweight/obese (body mass index (BMI) 33.4 ± 3.7 kg/m2), adults with knee OA enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) study. Participants were randomized to 18 months of walking and strength training (E; n = 95), dietary-induced weight loss targeting 10% of baseline weight (D; n = 88) or a combination of the two (D + E; n = 101). Body weight and composition (DXA), regional BMD, were obtained at baseline and 18 months. RESULTS: E, D, and D + E groups lost 1.3 ± 4.5 kg, 9.1 ± 8.6 kg and 10.4 ± 8.0 kg, respectively (P < 0.01). Significant treatment effects were observed for BMD in both hip and femoral neck regions, with the D and D + E groups showing similar relative losses compared to E (both P < 0.01). Despite reduced BMD, fewer overall participants had T-scores indicative of osteoporosis after intervention (9 at 18 months vs 10 at baseline). Within the D and D + E groups, changes in hip and femoral neck, but not spine, BMD correlated positively with changes in body weight (r = 0.21 and 0.54 respectively, both P ≤ 0.01). CONCLUSIONS: Weight loss via an intensive dietary intervention, with or without exercise, results in bone loss at the hip and femoral neck in overweight and obese, older adults with OA. Although the exercise intervention did not attenuate weight loss-associated reductions in BMD, classification of osteoporosis and osteopenia remained unchanged. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

Periaortic fat and cardiovascular risk: a comparison of high-risk older adults and age-matched healthy controls.

OBJECTIVE: Fat accumulation around the heart and aorta may impact cardiovascular (CV) health. The purpose of this study was to conduct a systematic investigation to examine potential associations of these fat depots with risk factors for CV events, which has not been done before. METHODS: Pericardial fat, periaortic fat around the ascending aorta (AA), descending aorta (DA) and aortic arch, and abdominal subcutaneous and visceral fat were measured by MRI in older adults with (n = 385, 69 ± 8 years, 52% female) and without (n = 50, 69 ± 8 years, 58% female) risk factors for a CV event. RESULTS: Individuals with CV risk factors exhibited greater fat volumes across all fat depots compared with those without risk factors. In analysis of covariance accounting for age, gender, race/ethnicity, diabetes, hypertension, coronary artery disease, smoking and body mass index (BMI), individuals with risk factors possessed higher epicardial, pericardial, AA, DA and abdominal visceral fat (P < 0.05). When matched one-to-one on age, gender, race/ethnicity and BMI, AA and DA fat were higher in those with versus without CV risk factors (P < 0.01). CONCLUSIONS: Older adults with a high risk for CV events have greater periaortic fat than low-risk adults, even after accounting for BMI. More studies are needed to determine whether greater periaortic fat predicts future CV events.

Basal growth hormone concentration increased following a weight loss focused dietary intervention in older overweight and obese women.

OBJECTIVES: Growth and sex steroid hormones decrease with aging and obesity. The effect of dietary weight loss and exercise training lifestyle interventions was examined on hormones as well as determining their relationships with physical function in older obese and overweight adults. DESIGN: Individuals were randomized into one of four 18 month interventions: Healthy Lifestyle (HL), Exercise, Diet, and Exercise-Diet. SETTING: Clinical research setting with facility based exercise and nutrition education and behavior classrooms. PARTICIPANTS: Older (≥60 yrs) overweight and obese (BMI≥28 kg/m(2)) adults with knee osteoarthritis (n=309) were recruited for the study. INTERVENTION: Weight loss goal for Diet groups was ≥5%. Exercise groups trained (mostly walking and resistance training) 3 days/week for 60 min/session. MEASUREMENTS: Body weight, growth hormone (GH), corticosterone, sex-hormone binding globulin (SHBG), testosterone, and dehydroepiandrosterone (DHEA) were measured at baseline, 6, and 18 months. Physical function was determined through performance task (6-min walking distance) and self-reported questionnaires (Western Ontario McMaster University Osteoarthritis Index-WOMAC) at similar time points. RESULTS: Diet, Exercise, and Exercise-Diet groups lost 4.9%, 3.5%, and 6.2% of their weight at 18 months, respectively. There was a significant diet treatment effect on GH levels in women as higher concentrations of this hormone were apparent following dietary weight loss intervention (p=0.01). No other hormones were affected by either diet or exercise treatments in men or women. A significant inverse correlation between baseline 6-minute walking distance and SHBG (r=-0.33) was found in men. CONCLUSION: The increase in basal GH levels from the diet treatment in women suggests that this lifestyle behavior intervention may mitigate the age- and obesity-related decreases in growth hormone levels, to help preserve muscle mass, strength, and physical function in older adults.

Caloric restriction, aerobic exercise training and soluble lectin-like oxidized LDL receptor-1 levels in overweight and obese post-menopausal women.

BACKGROUND: Elevated circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) have been observed in obese persons and are reduced by weight loss. However, it is not known whether combining caloric restriction (CR) with exercise training is better in reducing sLOX-1 levels than CR alone. OBJECTIVE: We examined whether the addition of aerobic exercise to a weight loss intervention differentially affects sLOX-1 levels in 61 abdominally obese post-menopausal women randomly assigned to a CR only (n = 22), CR+moderate-intensity exercise (n = 22) or CR+vigorous-intensity exercise (n = 17) intervention for 20 weeks. The caloric deficit was ~2800 kcal per week for all groups. RESULTS: The intervention groups were similar at baseline with respect to body weight, body composition, lipids and blood pressure. However, plasma sLOX-1 levels were higher in the CR-only group (99.90 ± 8.23 pg ml(-1)) compared with both the CR+moderate-intensity exercise (69.39 ± 8.23 pg ml(-1), P = 0.01) and the CR+vigorous-intensity exercise (72.83 ± 9.36 pg ml(-1), P = 0.03) groups. All three interventions significantly reduced body weight (~14%), body fat and waist and hip circumferences to a similar degree. These changes were accompanied by a 23% reduction in sLOX-1 levels overall (-19.00 ± 30.08 pg ml(-1), P < 0.0001), which did not differ among intervention groups (P = 0.13). Changes in body weight, body fat and maximal oxygen consumption (VO(2) max) were not correlated with changes in sLOX-1 levels. In multiple regression analyses in all women combined, baseline sLOX-1 levels (ß = -0.70 ± 0.06, P < 0.0001), age (ß = 0.92 ± 0.43, P = 0.03) and baseline body mass index (BMI) (ß = 1.88 ± 0.66, P = 0.006) were independent predictors of the change in sLOX-1 with weight loss. CONCLUSIONS: Weight loss interventions of equal energy deficit have similar effects on sLOX-1 levels in overweight and obese post-menopausal women, with the addition of aerobic exercise having no added benefit when performed in conjunction with CR.

Effects of dietary protein on the composition of weight loss in post-menopausal women.

OBJECTIVES: To determine whether a hypocaloric diet higher in protein can prevent the loss of lean mass that is commonly associated with weight loss. DESIGN: An intervention study comparing a hypocaloric diet moderately high in protein to one lower in protein. SETTING: Study measurements were taken at the Wake Forest University General Clinical Research Center (GCRC) and Geriatric Research Center (GRC). PARTICIPANTS: Twenty-four post-menopausal, obese women (mean age = 58 +/- 6.6 yrs; mean BMI = 33.0 +/- 3.6 kg/m2). INTERVENTION: Two 20-week hypocaloric diets (both reduced by 2800 kcal/wk) were compared: one maintaining dietary protein intake at 30% of total energy intake (1.2-1.5 g/kg/d; HI PROT), and the other maintaining dietary protein intake at 15% of total energy (0.5-0.7 g/kg/d; LO PROT). The GCRC metabolic kitchen provided lunch and dinner meals which the women picked up 3 days per week and ate outside of the clinic. MEASUREMENTS: Body composition, including total body mass, total lean mass, total fat mass, and appendicular lean mass, assessed by dual energy x-ray absorptiometry, was measured before and after the diet interventions. RESULTS: The HI PROT group lost 8.4 +/- 4.5 kg and the LO PROT group lost 11.4 +/- 3.8 kg of body weight (p = 0.11). The mean percentage of total mass lost as lean mass was 17.3% +/- 27.8% and 37.5% +/- 14.6%, respectively (p = 0.03). CONCLUSION: Maintaining adequate protein intake may reduce lean mass losses associated with voluntary weight loss in older women.

The association between weight history and physical performance in the Health, Aging and Body Composition study.

OBJECTIVE: Although the association between current obesity and physical disability is well known, the cumulative effect of obesity is unknown. Using data from the Health, Aging and Body Composition study, we examined the association between weight history in young and middle adulthood and weight status in late adulthood with physical performance in late adulthood. DESIGN: Longitudinal cohort study. SUBJECTS: White and black men and women aged 70-79 years at study baseline (n=2803). MEASURES: Body mass index (BMI; kg/m(2)) was calculated using recalled height at age 25 and weight at age 25 and 50 and measured height and weight at ages 70-79. Physical performance at ages 70-79 was assessed using a short physical performance battery (SPPB) and a 400-m walk test. RESULTS: In this well-functioning cohort, approximately 24% of men and 8% of women reported being overweight or obese (BMI > or =25 kg/m(2)) at age 25, 51% of men and 37% of women reported being overweight or obese at age 50, and 69% of men and 66% of women were overweight or obese at ages 70-79. Men and women who were obese (BMI > or =30 kg/m(2)) at ages 25, 50 and 70-79 had significantly worse SPPB scores and 400-m walk times than those who were normal weight. Women who were overweight (BMI 25-29.9 kg/m(2)) at ages 25, 50 and 70-79 also had significantly worse physical performance. Furthermore, men and women who had a history of being overweight or obese at ages 25 or 50 had worse physical performance compared to those who were normal weight throughout or who were overweight or obese at ages 70-79 but not in midlife or earlier. CONCLUSIONS: Maintaining a healthy body weight throughout adulthood may play a role in preventing or delaying the onset of physical disability.

Addition of aerobic exercise to dietary weight loss preferentially reduces abdominal adipocyte size.

OBJECTIVE: To determine if hypocaloric diet, diet plus low-intensity exercise, and diet plus high-intensity exercise differentially influence subcutaneous abdominal and gluteal adipocyte size in obese individuals. DESIGN: Longitudinal intervention study of hypocaloric diet, diet plus low-intensity exercise, and diet plus high-intensity exercise (calorie deficit = 2800 kcal/week, 20 weeks). SUBJECTS: Forty-five obese, middle-aged women (BMI = 33.0+/-0.6 kg/m2, age = 58+/-1 years). MEASUREMENTS: Body composition testing and adipose tissue biopsies were conducted before and after the interventions. Subcutaneous abdominal and gluteal adipocyte size was determined. RESULTS: All three interventions reduced body weight, fat mass, percent fat, and waist and hip girths to a similar degree. Diet only did not change subcutaneous abdominal adipocyte size, whereas both diet plus exercise groups significantly reduced abdominal adipocyte size. Changes in abdominal adipocyte size in the diet plus exercise groups were significantly different from that of the diet group. Gluteal adipocyte size decreased similarly in all three groups. CONCLUSION: Addition of exercise training to dietary weight loss preferentially reduces subcutaneous abdominal adipocyte size in obese women. This may be of importance for the treatment of health complications associated with subcutaneous abdominal adiposity.

Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study.

OBJECTIVE: Adipose tissue distribution (visceral vs subcutaneous) has been shown to be an important predictor of insulin resistance, diabetes and cardiovascular disease, independent of body mass index. The beta-2 adrenergic receptor is a major lipolytic receptor in human fat cells and the gene that codes for this protein is an important candidate gene for measures of adiposity and fat deposition. We examined whether two common polymorphisms in codons 16 (Arg16Gly) and 27 (Gln27Glu) are associated with measures of fat distribution in participants of the IRAS Family Study. METHODS: We recruited African-American (AA) and Hispanic-American (HA) families from Los Angeles, CA, USA (18 pedigrees, 272 AA individuals), San Antonio, TX, USA (33 pedigrees, 448 HA individuals) and San Luis Valley, CO, USA (12 pedigrees, 272 HA individuals). We estimated adipose tissue distribution via computed tomography. To test for an association between adiposity measures and these polymorphisms, we used generalized estimating equations, adjusting for age, gender, clinical site (ethnicity), body mass index, and familial correlation. RESULTS: Of the 992 individuals genotyped for these polymorphisms, 57% were female and 15% had been diagnosed with type 2 diabetes mellitus. The mean age was 42.7+/-14.6 y. The Glu27 allele of the Gln27Glu polymorphism was positively associated with (P-value for recessive model): body mass index (0.025), visceral adipose tissue (<0.0001) and visceral-to-subcutaneous adipose ratio (0.009), but not with subcutaneous adipose tissue (0.952). The Arg16Gly polymorphism was not associated with any of the adiposity measures. CONCLUSIONS: These findings suggest that genetic variation in the beta-2 adrenergic receptor gene influences fat deposition and body size in AAs and HAs. In particular, these results support a role for the gene in the distribution of visceral adipose tissue but not subcutaneous adipose tissue.