Impact on Cardiovascular Health of Using Phentermine/Topiramate in Combination With Laparoscopic Sleeve Gastrectomy in Super Obesity.

INTRODUCTION: Management of patients with BMI≥50 kg/m2 is challenging. In previous work, pre and postoperative pharmacotherapy with phentermine/topiramate plus laparoscopic sleeve gastrectomy (PT + SG) promoted greater weight loss than sleeve gastrectomy (SG) alone at 24 mo postoperatively. This current secondary analysis studied the impact of PT + SG on blood pressure (BP), heart rate, and antihypertensive usage. METHODS: Patients with BMI≥50 kg/m2 planning to have SG (n = 13) were recruited from 2014 to 2016, at an academic medical center in Winston-Salem, North Carolina, for this open-label trial. Participants took phentermine/topiramate (PT; 7.5/46-15/92 mg/d) for ≥3 mo preoperatively and 24 mo postoperatively. The control group (n = 40) underwent SG during the same time frame. We used mixed models for BP and heart rate to compare PT + SG versus SG alone over time, adjusted for age, sex, and initial BP. RESULTS: By 24 mo postoperatively the model adjusted changes in systolic blood pressure/diastolic blood pressure (SBP/DBP) (mm Hg) were -24.44 (-34.46,-14.43)/-28.60 (-40.74,-16.46) in the PT + SG group versus -11.81 (-17.58,-6.05)/-13.89 (-21.32,-6.46) in the control group (SBP P = 0.02; DBP P = 0.03). At baseline 8 (61.5%) participants in the PT + SG arm and 22 (55.0%) in the control group used antihypertensives. Excluding patients lost to follow-up (n = 3), by 24 mo postoperatively, none of the PT + SG participants were on antihypertensives compared to 14 (41.2%) in the control group (P = 0.01). CONCLUSIONS: Patients with BMI≥50 kg/m2 treated with PT + SG had greater improvement in BP with no use of antihypertensive medication at 24 mo postoperatively versus SG alone, where 41% continued medication use. Larger trials are required to evaluate this.

End-of-Trial Health Outcomes in Look AHEAD Participants who Elected to have Bariatric Surgery.

OBJECTIVE: This study examined end-of-trial health outcomes in participants in the Action for Health in Diabetes (Look AHEAD) trial who had bariatric surgery during the approximately 10-year randomized intervention. METHODS: Data were obtained from the Look AHEAD public access database of 4,901 individuals with type 2 diabetes and overweight/obesity who were assigned to intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group. Changes in outcomes in participants who had bariatric surgery were compared with those in participants with BMI ≥ 30 kg/m2 who remained in the ILI and DSE groups. RESULTS: A total of 99 DSE and 97 ILI participants had bariatric surgery. At randomization, these 196 participants were significantly younger and more likely to be female and to have higher BMI than the remaining ILI (N = 1,972) and DSE (N = 2,009) participants. At trial's end, surgically treated participants lost 19.3% of baseline weight, compared with 5.8% and 3.3% for the ILI and DSE groups, respectively, and were more likely to achieve partial or full remission of their diabetes. CONCLUSIONS: The large, sustained improvements in weight and diabetes observed in this self-selected sample of surgically treated participants are consistent with results of multiple randomized trials.

Relationship of Objectively-Measured Habitual Physical Activity to Chronic Inflammation and Fatigue in Middle-Aged and Older Adults.

BACKGROUND: Habitual (non-exercise) physical activity (PA) declines with age, and aging-related increases in inflammation and fatigue may be important contributors to variability in PA. METHODS: This study examined the association of objectively-measured PA (accelerometry over 7 days) with inflammation (plasma interleukin-6 and C-reactive protein) and with self-reported fatigue (SF-36 Vitality) at baseline and 18 months after a diet-induced weight loss, exercise, or diet-induced weight loss plus exercise intervention in 167 overweight/obese, middle-aged, and older adults. RESULTS: At baseline, individuals with higher plasma interleukin-6, as well as those who reported feeling less energetic (more fatigued), took less steps per day and had lower PA energy expenditure and minutes of light and moderate-vigorous PA (p < .05 for all). At the 18-month follow-up, inflammation was lower in both weight loss groups, fatigue was reduced in all three groups with larger decreases in the combined group, and mean levels of habitual PA were not changed in any group. In longitudinal analyses with all groups combined, we found that participants reporting larger increases in vitality (eg, declines in fatigue) had greater increases in PA (p < .05 for all). Also, changes in steps/d and physical activity energy expenditure were indirectly associated with changes in interleukin-6 (ß [SEM] for steps/d = -565 [253]; ß [SEM] for physical activity energy expenditure = -22.4 [10.17]; p < .05). CONCLUSIONS: Levels of habitual PA are lower in middle-aged and older adults with higher levels of chronic inflammation and greater self-reported fatigue. In addition, participants who experienced greater declines in inflammation during the interventions had greater declines in fatigue and larger increases in PA.

Effects of a community-based weight loss intervention on adipose tissue circulating factors.

AIMS: Obesity is associated with metabolic dysfunctions, which may be mediated by changes in adipose tissue signaling factors. These molecules are denoted as Adipose Tissue Generated Mediators of CardioVascular Risk (ATGMCVR) here, and include leptin, adiponectin, C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and plasminogen activator inhibitor 1 (PAI-1). This study examined the effect of a weight loss program on ATGMCVR in obese adults with prediabetes. MATERIALS AND METHODS: Subjects were randomized to usual care (UC; n=15) or lifestyle weight loss groups (LWL; n=15). LWL was a community-based weight loss intervention to promote physical activity and healthy eating. ATGMCVR at 1-year were compared between groups by analysis of covariance; baseline value of the mediator was the covariate. Baseline means for ATGMCVR were compared between those with (n=21) and without (n=9) metabolic syndrome (MetS). RESULTS: At baseline, subjects were 58±9 (SD) years, 70% female, with a BMI of 34±4kg/m(2). One-year weight loss (%) was 7.8±6.0% for LWL and 1.7±4.5% for UC. Group differences at 1-year were noted (adjusted means [95%CI] for UC and LWL, respectively) for adiponectin (8526.3 [7397.7, 9827]; 10,870.9 [9432.0, 12,529.3]ng/ml; p=0.02), leptin (30.4 [26.1, 35.4]; 23.7 [20.3, 27.5]ng/ml; p=0.02), IL-6 (0.4 [0.3, 0.5]; 0.2 [0.1, 0.2] pg/ml; p=0.001), and PAI-1 (50 [42.7, 58.7]; 36.2 [30.8, 42.4]pg/ml; p=0.01). No differences in baseline ATGMCVR were seen between subjects with and without MetS. CONCLUSION: These findings suggest ATGMCVR can be improved with weight loss; larger studies are needed to determine if improvements in metabolic dysfunction are related to changes in ATGMCVR.

Changes in nutrients and food groups intake following laparoscopic Roux-en-Y gastric bypass (RYGB).

BACKGROUND: Serial changes in dietary intake, including specific food groups and nutrients during the first year following Roux-en-Y gastric bypass (RYGB) are of interest due to surgically induced alterations in meal size, food intolerances present after surgery, and potential nutrient deficiencies. To help improve the nutritional health of surgical patients, this study's purpose was to examine changes in macro- and micronutrients, food groups, and selected foods during 12 months of follow-up in post-RYGB individuals. METHODS: RYGB patients (n = 17) completed 4-day food records at baseline (prior to surgery) and then at 3 weeks, 3 months, 6 months, and 12 months after surgery. Mean daily intake was determined at each time for energy intake, macro- and micronutrients, food groups, and selected foods in targeted food groups. RESULTS: A dramatic decrease in mean (± SEM) daily energy intake occurred--2,150 ± 165 kcal at baseline vs. 649 ± 40 kcal at 3 weeks; energy intake continually increased to a high of 1,307 ± 129 kcal by 12 months. More than 50 % of patients had low intake of vitamins D, E, C, folate, and calcium, magnesium, and potassium at 12 months. Servings from vegetables, grains, fats, and sweetened beverages were lower, whereas, meats, dairy, fruits, and sweets showed only small, transient changes following surgery. CONCLUSIONS: The reduction in energy intake following RYGB is from selected food groups and not solely a reduction in portion sizes across the diet. The lower intake of micronutrients indicates potential risk for deficiencies unless supplements are used. These findings can help in the clinical management of surgical patients to improve nutritional health.

Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial.

IMPORTANCE: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ](exercise vs diet )= 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δ(exercise vs diet + exercise) = 0.39 pg/mL; 95% CI, -0.03 to 0.81; P = .007; Δ(exercise vs diet )= 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δ(exercise vs diet + exercise) = 1.02; 95% CI, 0.33 to 1.71; P(pain) = .004; 18.4; 95% CI, 16.9 to 19.9; Δ(exercise vs diet + exercise), 4.29; 95% CI, 2.07 to 6.50; P(function )< .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δ(exercise vs diet + exercise) = -2.81; 95% CI, -4.76 to -0.86; P = .005). CONCLUSIONS AND RELEVANCE: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00381290.

Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery.

BACKGROUND: A number of proteins secreted from adipose tissue, known as adipokines, are involved in the inflammatory process. The expression and secretion of adipokines are altered with obesity, leading to a pro-inflammatory state, with an enhanced vascular immune response. Although weight loss reduces inflammation, the time course for these changes during massive weight loss after bariatric surgery is not well described. We examined the changes in the biomarkers of inflammation after laparoscopic Roux-en-Y gastric bypass (RYGB) in morbidly obese individuals in a university hospital. METHODS: The fasting levels of plasma inflammatory adipokines, including leptin, adiponectin, C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α), and soluble receptor 1 for TNF-α were measured before surgery (baseline) and 3 weeks, 3 months, and 6 months after surgery in 15 morbidly obese patients who underwent Roux-en-Y gastric bypass without a major complication. RESULTS: The mean weight loss at 6 months was 25.7% ± 4.5% of the total body weight. The body mass index decreased from a mean of 55.1 ± 6.6 kg/m(2) to 40.5 ± 5.5 kg/m(2). The concentrations of leptin, CRP, and soluble receptor 1 for TNF-α decreased, and the adiponectin levels had increased from the baseline measures by 6 months postoperatively. The baseline and 6-month TNF-α and CRP levels correlated with each other. No other significant associations among the biomarkers were seen. CONCLUSION: RYGB reduced the pro-inflammatory biomarkers and increased the anti-inflammatory mediators of obesity, independent of the magnitude of weight loss. The lack of correlations between the changes in biomarkers and weight loss suggests that the driving force behind the changes in the inflammatory markers is multifactorial and needs further investigation to clarify the health changes that occur after RYGB.

The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

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/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) 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 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), 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 cm(3), P = 0.005; women: -34 vs. -59 cm(3), 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.

Physical function improvements after laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: Obesity is a risk factor for impaired physical function and disability, with the degree of impairment most compromised in extreme obesity. Mild-to-moderate weight loss has been shown to improve function in older adults. The impact of laparoscopic Roux-en-Y gastric bypass surgery on weight loss and physical function in morbidly obese individuals was assessed. METHODS: This longitudinal, observational study followed up 28 morbidly obese men and women (body mass index > or = 40.0 kg/m(2)) for 12 months after laparoscopic Roux-en-Y gastric bypass. Physical function (self-report using the Fitness Arthritis and Seniors Trial disability questionnaire; performance tasks using the Short Physical Performance Battery and a lateral mobility task); strength (maximal isometric knee torque); and body composition measured using bioelectrical impedance were determined before surgery (baseline) and at 3 weeks, 3 months, 6 months, and 12 months after surgery. RESULTS: The 12-month weight loss was 34.2% (excess weight loss 59.8%), with a mean fat mass loss of 46 kg and a loss of fat free mass of 6.6 kg. The performance tasks and self-reported questionnaire scores had improved by 3 months after surgery compared with baseline, with selected measures showing less impairment and disability in as few as 3 weeks after surgery. Muscle quality, as measured using the maximal torque per kilogram body weight, was greater at 6 months than at baseline. CONCLUSION: The results of our study have shown that in morbidly obese individuals with a high risk of mobility impairments, surgical procedures to reduce body weight increase mobility and improve performance of daily activities in as few as 3 weeks after gastric bypass surgery.

Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy.

OBJECTIVES: To describe the relationships between proinflammatory biomarkers and self-reported and performance-based physical function and to examine the effect of weight loss on these markers of inflammation. DESIGN: Randomized, longitudinal, clinical study comparing subjects eating an energy-restricted diet and participating in exercise training with a control group. SETTING: Community-base participants for the Physical Activity, Inflammation and Body Composition Trial. PARTICIPANTS: Eighty-seven obese (body mass index (BMI) >30.0 kg/m(2)) adults aged 60 and older with knee pain and self-report of osteoarthritis. MEASUREMENTS: Inflammatory biomarkers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), C-reactive protein, and soluble receptors for TNFalpha (sTNFR1 and sTNFR2)) and self-reported (Western Ontario and McMaster University Osteoarthritis Index questionnaire) and performance-based (6-minute walk distance and stair climb time) measures of physical function at baseline and 6 months. RESULTS: Mean (standard error of the mean) weight loss was 8.7% (0.8%) in the intervention group, compared with 0.0% (0.7%) in the control group. sTNFR1 was significantly less in the intervention group than in the control group at 6 months. sTNFR1 and sTNFR2 predicted stair climb time at baseline. Change across the 6-month intervention for sTNFR2 was an independent predictor for change in 6-minute walk distance. CONCLUSION: These results indicate that an intensive weight-loss intervention in older obese adults with knee pain can help improve inflammatory biomarkers and that changes in these concentrations showed associations with physical function.

Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial.

BACKGROUND: Persistent, low-grade inflammation is an independent predictor of several chronic diseases and all-cause mortality. OBJECTIVE: The intention of this study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation. DESIGN: Three hundred sixteen community-dwelling, older (> or = 60 y), overweight or obese [body mass index (in kg/m2) > or = 28], sedentary men and women with radiographic evidence of knee osteoarthritis were randomly assigned to four 18-mo treatments: healthy lifestyle control, diet-induced weight loss, exercise, and diet plus exercise. The exercise intervention consisted of combined weight training and walking for 1 h 3 times/wk. The weight-loss intervention consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake. RESULTS: The diet-induced weight-loss intervention resulted in significantly greater reductions in concentrations of C-reactive protein (P = 0.01), interleukin 6 (P = 0.009), and soluble tumor necrosis factor alpha receptor 1 (P = 0.007) than did no weight-loss treatment. Changes in soluble tumor necrosis factor alpha receptor 1 but not in C-reactive protein or interleukin 6 correlated with changes in body weight. Exercise training did not have a significant effect on these inflammatory biomarkers, and there was no significant interaction between weight loss and exercise training. CONCLUSIONS: These findings provide evidence from a randomized controlled trial that a dietary intervention designed to elicit weight loss reduces overall inflammation in older, obese persons. Additional studies are needed to assess the effects of different modes and intensities of exercise on inflammation.

The Arthritis, Diet and Activity Promotion Trial (ADAPT): design, rationale, and baseline results.

Osteoarthritis (OA) of the knee leads to restrictions of physical activity and ability to perform activities of daily living. Obesity is a risk factor for knee OA and it appears to exacerbate knee pain and disability. The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was developed to test the efficacy of lifestyle behavioral changes on physical function, pain, and disability in obese, sedentary older adults with knee OA. This controlled trial randomized 316 sedentary overweight and obese older adults in a two-by-two factorial design into one of four 18-month duration intervention groups: Healthy Lifestyle Control; Dietary Weight Loss; Structured Exercise; or Combined Exercise and Dietary Weight Loss. The weight-loss goal for the diet groups was a 5% loss at 18 months. The intervention was modeled from principles derived from the group dynamics literature and social cognitive theory. Exercise training consisted of aerobic and strength training for 60 minutes, three times per week in a group and home-based setting. The primary outcome measure was self-report of physical function using the Western Ontario and McMaster University Osteoarthritis Index. Other measurements included timed stair climb, distance walked in 6 minutes, strength, gait, knee pain, health-related quality of life, knee radiographs, body weight, dietary intake, and cost-effectiveness of the interventions. We report baseline data stratified by level of overweight and obesity focusing on self-reported physical function and physical performance tasks. The results from ADAPT will provide approaches clinicians should recommend for behavioral therapies that effectively reduce the incidence of disability associated with knee OA.