Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.

OBJECTIVE: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Multi-sensor ecological momentary assessment of behavioral and psychosocial predictors of weight loss following bariatric surgery: study protocol for a multicenter prospective longitudinal evaluation.

BACKGROUND: Bariatric surgery is currently the most effective strategy for producing significant and durable weight loss. Yet, not all patients achieve initial weight loss success and some degree of weight regain is very common, sometimes as early as 1-2 years post-surgery. Suboptimal weight loss not fully explained by surgical, demographic, and medical factors has led to greater emphasis on patient behaviors evidenced by clinical guidelines for appropriate eating and physical activity. However, research to inform such guidelines has often relied on imprecise measures or not been specific to bariatric surgery. There is also little understanding of what psychosocial factors and environmental contexts impact outcomes. To address research gaps and measurement limitations, we designed a protocol that innovatively integrates multiple measurement tools to determine which behaviors, environmental contexts, and psychosocial factors are related to outcomes and explore how psychosocial factors/environmental contexts influence weight. This paper provides a detailed description of our study protocol with a focus on developing and deploying a multi-sensor assessment tool to meet our study aims. METHODS: This NIH-funded prospective cohort study evaluates behavioral, psychosocial, and environmental predictors of weight loss after bariatric surgery using a multi-sensor platform that integrates objective sensors and self-report information collected via smartphone in real-time in patients' natural environment. A target sample of 100 adult, bariatric surgery patients (ages 21-70) use this multi-sensor platform at preoperative baseline, as well as 3, 6, and 12 months postoperatively, to assess recommended behaviors (e.g., meal frequency, physical activity), psychosocial indicators with prior evidence of an association with surgical outcomes (e.g., mood/depression), and key environmental factors (e.g., type/quality of food environment). Weight also is measured at each assessment point. DISCUSSION: This project has the potential to build a more sophisticated and valid understanding of behavioral and psychosocial factors contributing to success and risk after bariatric surgery. This new understanding could directly contribute to improved (i.e., specific, consistent, and validated) guidelines for recommended pre- and postoperative behaviors, which could lead to improved surgical outcomes. These data will also inform behavioral, psychosocial, and environmental targets for adjunctive interventions to improve surgical outcomes. TRIAL REGISTRATION: Registered trial NCT02777177 on 5/19/2016.

Weight Loss After Bariatric Surgery: Do Clinical and Behavioral Factors Explain Racial Differences?

BACKGROUND: Prior studies have suggested less weight loss among African American compared to Caucasian patients; however, few studies have been able to simultaneously account for baseline differences in other demographic, clinical, or behavioral factors. METHODS: We interviewed patients at two weight loss surgery (WLS) centers and conducted chart reviews before and after WLS. We compared weight loss post-WLS by race/ethnicity and examined baseline demographic, clinical (BMI, comorbidities, quality of life), and behavioral (eating behavior, physical activity level, alcohol intake) factors that might explain observed racial differences in weight loss at 1 and 2 years after WLS. RESULTS: Of 537 participants who underwent either Roux-en-Y Gastric Bypass (54%) or gastric banding (46%), 85% completed 1-year follow-up and 73% completed 2-year follow-up. Patients lost a mean of 33.00% of initial weight at year 1 and 32.43% at year 2 after bypass and 16.07% and 17.56 % respectively after banding. After adjustment for other demographic characteristics and type of surgery, African Americans lost an absolute 5.93 ± 1.49% less weight than Caucasian patients after bypass (p < 0.001) and 4.72 ± 1.96% less weight after banding. Of the other demographic, clinical, behavioral factors considered, having diabetes and perceived difficulty making dietary changes at baseline were associated with less weight loss among gastric bypass patients whereas having a diagnosis of anxiety disorder was associated with less weight loss among gastric banding patients. The association between race and weight loss did not substantially attenuate with additional adjustment for these clinical and behavioral factors, however. CONCLUSION: African American patients lost significantly less weight than Caucasian patients. Racial differences could not be explained by baseline demographic, clinical, or behavioral characteristics we examined.

Effects of Longitudinal Glucose Exposure on Cognitive and Physical Function: Results from the Action for Health in Diabetes Movement and Memory Study.

OBJECTIVES: To test whether average long-term glucose exposure is associated with cognitive and physical function in middle-aged and younger-old adults with type 2 diabetes mellitus. DESIGN: Prospective cohort study. SETTING: Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Movement and Memory ancillary study (NCT01410097). PARTICIPANTS: Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 at baseline (N = 879). MEASUREMENTS: Glycosylated hemoglobin (HbA1c) was measured at regular intervals over 7 years, and objective measures of cognitive function (Trail-Making Test, Modified Stroop Color-Word Test, Digit Symbol-Coding, Rey Auditory Verbal Learning Test, Modified Mini-Mental State Examination) and physical function (Short Physical Performance Battery, expanded Physical Performance Battery, 400-m and 20-m gait speed) and strength (grip and knee extensor strength) were assessed at the Year 8 or 9 follow-up examination. RESULTS: Average HbA1c exposure was 7.0 ± 1.1% (53 ± 11.6 mmol/mol), with 57% of participants classified as having HbA1c levels of less than 7% (<53 mmol/mol), 27% having levels of 7% to 8% (53-64 mmol/mol), and 16% having levels of greater than 8% (>64 mmol/mol). After adjustment for age, sex, race, education, smoking status, alcohol intake, knee pain, physical fitness, body mass index, diabetes mellitus medication and statin use, ancillary year visit, and study arm and site, higher HbA1c was associated with worse physical but not cognitive function. Further adjustment for prevalent diabetes mellitus-related comorbidities made all associations nonsignificant. Results did not differ when stratified according to participant baseline age (<60 vs ≥ 60). CONCLUSION: Results presented here suggest that, in the absence of diabetes mellitus-related complications, longitudinal glucose exposure is not associated with future cognitive and physical function. Optimal management of diabetes mellitus-related comorbidities may prevent or reduce the burden of disability associated with type 2 diabetes mellitus.

No effect of caloric restriction or exercise on radiation repair capacity.

INTRODUCTION: Maintenance of normal weight and higher levels of physical activity are associated with a reduced risk of several types of cancer. Because genomic instability is regarded as a hallmark of cancer development, one proposed mechanism is improvement of DNA repair function. We investigated links between dietary weight loss, exercise, and strand break rejoining in an ancillary study to a randomized-controlled trial. METHODS: Overweight/obese postmenopausal women (n = 439) were randomized to the following: a) reduced calorie weight loss diet ("diet," n = 118), b) moderate- to vigorous-intensity aerobic exercise ("exercise," n = 117), c) a combination ("diet + exercise," n = 117), or d) control (n = 87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 min of moderate to vigorous aerobic activity 5 d·wk for 12 months. DNA repair capacity was measured in a subset of 226 women at baseline and 12 months from cryopreserved peripheral mononuclear cells using the comet assay. Anthropometric and body composition measures were performed at baseline and 12 months. RESULTS: DNA repair capacity did not change significantly with any of the 12-month interventions compared with control; there were also no significant changes when stratified by changes in body composition or aerobic fitness (V˙O2max). At baseline, DNA repair capacity was positively associated with weight, body mass index, and fat mass (r = 0.20, P = 0.003; r = 0.19, P = 0.004; r = 0.13, P = 0.04, respectively) and inversely with lean body mass (r = -0.14, P = 0.04). CONCLUSION: In conclusion, DNA repair capacity in cryopreserved PBMCs (Comet Assay) did not change with dietary weight loss or exercise interventions in postmenopausal women within a period of 12 months. Other assays that capture different facets of DNA repair function may be needed.

Patient race and the likelihood of undergoing bariatric surgery among patients seeking surgery.

BACKGROUND: Ethnic minority adults have disproportionately higher rates of obesity than Caucasians but are less likely to undergo bariatric surgery. Recent data suggest that minorities might be less likely to seek surgery. Whether minorities who seek surgery are also less likely to proceed with surgery is unclear. METHODS: We interviewed 651 patients who sought bariatric surgery at two academic medical centers to examine whether ethnic minorities are less likely to proceed with surgery than Caucasians and whether minorities who do proceed with surgery have higher illness burden than their counterparts. We collected patient demographics and abstracted clinical data from the medical records. We then conducted multivariable analyses to examine the association between race and the likelihood of proceeding with bariatric surgery within 1 year of initial interview and to compare the illness burden by race and ethnicity among those who underwent surgery. RESULTS: Of our study sample, 66% were Caucasian, 18% were African-American, and 12% were Hispanics. After adjustment for socioeconomic factors, there were no racial differences in who proceeded with bariatric surgery. Among those who proceeded with surgery, illness burden was comparable between minorities and Caucasian patients with the exception that African-Americans were underrepresented among those with reflux disease (0.4, 95% CI 0.2-0.7) and depression (0.4, 0.2-0.7), and overrepresented among those with anemia (4.8, 2.4-9.6) than Caucasian patients. CONCLUSIONS: Race and ethnicity were not independently associated with likelihood of proceeding with bariatric surgery. Minorities who proceeded with surgery did not clearly have higher illness burden than Caucasian patients.

Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

PURPOSE: Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. PATIENTS AND METHODS: We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. RESULTS: Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. CONCLUSION: A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed.

High-risk alcohol use after weight loss surgery.

BACKGROUND: Bariatric or weight loss surgery (WLS) may alter alcohol metabolism resulting in a higher prevalence of problem drinking postoperatively. Few studies distinguish those who report improvements in drinking from those who report worsening behavior after surgery. The objective of this study was to characterize high-risk alcohol use before and after WLS and according to surgery type. METHODS: We interviewed patients before and annually after WLS. High-risk alcohol use as assessed via a modified version of the Alcohol Use Disorders Identification Test-Consumption. RESULTS: Of 541 participants who underwent WLS, 375 (69% retention) completed the 1-year interview and 328 (63% retention) completed the 2-year interview. At 1 year, 13% reported high-risk drinking compared to 17% at baseline, P = .10; at year 2, 13% reported high-risk drinking compared to 15% at baseline, P = .39; 7% and 6% of patients, respectively, reported new high-risk drinking at 1- and 2-year follow-up. At both follow-up time points, more than half of those who reported high-risk drinking at baseline no longer did so. A larger proportion of gastric bypass patients (71%) reported amelioration in high-risk drinking than gastric banding (48%) at year 1, but this difference did not reach statistical significance (P = .07); the difference largely dissipated by year 2 (50% versus 57%) . CONCLUSION: Although 7% of patients report new high-risk alcohol use 1 year after WLS, more than half who reported high-risk alcohol use before surgery discontinued high-risk drinking.

Patient factors associated with undergoing laparoscopic adjustable gastric banding vs Roux-en-Y gastric bypass for weight loss.

BACKGROUND: Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding are 2 commonly performed bariatric procedures in the US with different profiles for risk and effectiveness. Little is known about factors that might lead patients to proceed with one procedure over the other. STUDY DESIGN: We recruited and interviewed patients seeking bariatric surgery from 2 academic centers in Boston (response rate 70%). We conducted multivariable analyses to identify patient perceptions and clinical and behavioral characteristics that correlated with undergoing gastric banding (n = 239) vs gastric bypass (n = 297). RESULTS: After adjustment for socio-demographic and clinical factors, we found that older patients (odds ratio [OR] 1.03; 95% CI 1.00 to 1.05) and those with higher quality of life scores and higher levels of uncontrolled eating were more likely to undergo gastric banding as opposed to gastric bypass. In contrast, patients with type 2 diabetes (OR 0.46; 95% CI 0.28 to 0.77), those who desired greater weight loss, and those who were willing to assume higher mortality risk to achieve their ideal weight were less likely to proceed with gastric banding. After initial adjustment, male sex and lower body mass index were associated with a likelihood of undergoing gastric banding; however, these factors were no longer significant after adjustment for other significant correlates such as patients' perceived ideal weight, predilection to assume risk to lose weight, and eating behavior. CONCLUSIONS: Patients' diabetes status, quality of life, eating behavior, ideal weight loss, and willingness to assume mortality risk to lose weight were associated with whether patients proceeded with gastric banding as opposed to gastric bypass. Other clinical factors were less important.

Effects of dietary weight loss and exercise on insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in postmenopausal women: a randomized controlled trial.

High levels of insulin-like growth factor (IGF)-I may increase the risk of common cancers in humans. We hypothesized that weight loss induced by diet and/or exercise would reduce IGF-I in postmenopausal women. Four hundred and thirty nine overweight or obese [body mass index (BMI) ≥ 25 kg/m(2)] women (50-75 years) were randomly assigned to: (i) exercise (N = 117), (ii) dietary weight loss (N = 118), (iii) diet + exercise (N = 117), or (iv) control (N = 87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 minutes/day, 5 days/week of moderate-to-vigorous intensity activity. Fasting serum IGF-I and IGF-binding protein (IGFBP)-3 were measured at baseline and 12 months by radioimmunoassay. Higher baseline BMI was associated with lower IGF-I and IGF-I/IGFBP-3 molar ratio. Although no significant changes in either IGF-I or IGFBP-3 were detected in any intervention arm compared with control, the IGF-I/IGFBP-3 ratio increased significantly in the diet (+5.0%, P < 0.01) and diet + exercise (+5.4%, P < 0.01) groups compared with control. Greater weight loss was positively associated with change in both IGF-I (P(trend) = 0.017) and IGF-I/IGFBP-3 ratio (P(trend) < 0.001) in the diet group, but inversely with change in IGFBP-3 in the diet + exercise group (P(trend) = 0.01). No consistent interaction effects with baseline BMI were detected. Modified IGF-I bioavailability is unlikely to be a mechanism through which caloric restriction reduces cancer risk in postmenopausal women.

Expectations for weight loss and willingness to accept risk among patients seeking weight loss surgery.

IMPORTANCE: Weight loss surgery (WLS) has been shown to produce long-term weight loss but is not risk free or universally effective. The weight loss expectations and willingness to undergo perioperative risk among patients seeking WLS remain unknown. OBJECTIVES: To examine the expectations and motivations of WLS patients and the mortality risks they are willing to undertake and to explore the demographic characteristics, clinical factors, and patient perceptions associated with high weight loss expectations and willingness to assume high surgical risk. DESIGN: We interviewed patients seeking WLS and conducted multivariable analyses to examine the characteristics associated with high weight loss expectations and the acceptance of mortality risks of 10% or higher. SETTING: Two WLS centers in Boston. PARTICIPANTS: Six hundred fifty-four patients. MAIN OUTCOME MEASURES: Disappointment with a sustained weight loss of 20% and willingness to accept a mortality risk of 10% or higher with WLS. RESULTS: On average, patients expected to lose as much as 38% of their weight after WLS and expressed disappointment if they did not lose at least 26%. Most patients (84.8%) accepted some risk of dying to undergo WLS, but only 57.5% were willing to undergo a hypothetical treatment that produced a 20% weight loss. The mean acceptable mortality risk to undergo WLS was 6.7%, but the median risk was only 0.1%; 19.5% of all patients were willing to accept a risk of at least 10%. Women were more likely than men to be disappointed with a 20% weight loss but were less likely to accept high mortality risk. After initial adjustment, white patients appeared more likely than African American patients to have high weight loss expectations and to be willing to accept high risk. Patients with lower quality-of-life scores and those who perceived needing to lose more than 10% and 20% of weight to achieve "any" health benefits were more likely to have unrealistic weight loss expectations. Low quality-of-life scores were also associated with willingness to accept high risk. CONCLUSIONS AND RELEVANCE: Most patients seeking WLS have high weight loss expectations and believe they need to lose substantial weight to derive any health benefits. Educational efforts may be necessary to align expectations with clinical reality.

History of weight cycling does not impede future weight loss or metabolic improvements in postmenopausal women.

OBJECTIVE: Given that the repetitive loss and regain of body weight, termed weight cycling, is a prevalent phenomenon that has been associated with negative physiological and psychological outcomes, the purpose of this study was to investigate weight change and physiological outcomes in women with a lifetime history of weight cycling enrolled in a 12-month diet and/or exercise intervention. METHODS: 439 overweight, inactive, postmenopausal women were randomized to: i) dietary weight loss with a 10% weight loss goal (N=118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week (n=117); ii) both dietary weight loss and exercise (n=117); or iv) control (n=87). Women were categorized as non-, moderate- (≥3 losses of ≥4.5 kg), or severe-cyclers (≥3 losses of ≥9.1 kg). Trend tests and linear regression were used to compare adherence and changes in weight, body composition, blood pressure, insulin, C-peptide, glucose, insulin resistance (HOMA-IR), C-reactive protein, leptin, adiponectin, and interleukin-6 between cyclers and non-cyclers. RESULTS: Moderate (n=103) and severe (n=77) cyclers were heavier and had less favorable metabolic profiles than non-cyclers at baseline. There were, however, no significant differences in adherence to the lifestyle interventions. Weight-cyclers (combined) had a greater improvement in HOMA-IR compared to non-cyclers participating in the exercise only intervention (P=.03), but no differences were apparent in the other groups. CONCLUSION: A history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes.

Prevalence of preoperative alcohol abuse among patients seeking weight-loss surgery.

BACKGROUND: It has been hypothesized that alcohol metabolism is altered after weight-loss surgery (WLS), with a few studies suggesting a high prevalence of postoperative problem drinking. However, many of these studies were methodologically limited by lack of preoperative alcohol use data, high loss to follow-up, and/or nonsystematic ascertainment of alcohol (ETOH) intake. We sought to systematically characterize ETOH use among WLS patients before surgery. METHODS: We recruited patients seeking WLS from May 2008 through November 2010 from two bariatric centers in Boston (response rate 75 %). Alcohol intake and problem-drinking behavior was systematically assessed in detail via phone interview among 653 obese patients before WLS. We used multivariable models to characterize alcohol drinking patterns and to examine the relationship between problem drinking and the likelihood of proceeding with WLS. RESULTS: At baseline, 29 % were nondrinkers, 55 % were social drinkers, and 16 % were problem drinkers, including 4 % who displayed alcohol abuse behavior. After adjustment, men and younger adults were significantly more likely to be high-risk drinkers. Problem drinkers were as likely as social drinkers to proceed with WLS. CONCLUSION: Results from this large representative study suggest a high prevalence of high-risk alcohol use behavior among patients seeking WLS. Detailed assessment of alcohol use may be warranted in clinical settings and in studies of alcohol use and WLS.

Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial.

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 min/wk 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. Four hundred and thirty-eight (N = 1 in diet + exercise group was excluded) were analyzed. Relative to controls, hs-CRP decreased by geometric mean (95% confidence interval, P value): 0.92 mg/L (0.53-1.31, P < 0.001) in the diet and 0.87 mg/L (0.51-1.23, P < 0.0001) in the diet + exercise groups. IL-6 decreased by 0.34 pg/mL (0.13-0.55, P = 0.001) in the diet and 0.32 pg/mL (0.15-0.49, P < 0.001) in the diet + exercise groups. Neutrophil counts decreased by 0.31 × 10(9)/L (0.09-0.54, P = 0.006) in the diet and 0.30 × 10(9)/L (0.09-0.50, P = 0.005) in the diet + exercise groups. Diet and diet + exercise participants with 5% or more weight loss reduced inflammatory biomarkers (hs-CRP, SAA, and IL-6) compared with 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.

Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: randomized controlled trial.

PURPOSE: 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/m(2), 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). RESULTS: Mean age and body mass index were 58 years and 30.9 kg/m(2), 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. CONCLUSION: Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.

Effect of diet and exercise, alone or combined, on weight and body composition in overweight-to-obese postmenopausal women.

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 toward 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 day/week. 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/m(2) 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. Three hundred and ninety nine 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), whereas the C group experienced a nonsignificant -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.

Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis.

OBJECTIVE: Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil. METHODS: HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing ∼19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d. RESULTS: Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control). CONCLUSION: We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms.

Effects of weight loss on serum vitamin D in postmenopausal women.

BACKGROUND: Low concentrations of circulating vitamin D are common with obesity and may represent a potential mechanism explaining the elevated risk of certain cancers and cardiovascular outcomes observed in individuals who are overweight or obese. OBJECTIVE: The objective of this study was to investigate the effects of 12 mo of weight loss through caloric restriction, exercise intervention, or both on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN: Overweight and obese postmenopausal women (n = 439) were randomly assigned to 1 of 4 groups: 1) diet modification (n = 118), 2) exercise (n = 117), 3) diet + exercise (n = 117), or 4) control (n = 87). The diet intervention was a group-based reduced-calorie program with a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous intensity aerobic activity daily for 5 d/wk. Serum 25(OH)D concentrations were measured by using a competitive chemiluminescent immunoassay at baseline and 12 mo. RESULTS: No significant change in serum 25(OH)D was found between the intervention and control groups. Women who lost <5%, 5-9.9%, 10-14.9%, or ≥15% of baseline weight had mean increases in 25(OH)D of 2.1, 2.7, 3.3, and 7.7 ng/mL, respectively (P for trend = 0.002). Baseline vitamin D status did not modify the effect of the interventions on weight loss or body-composition changes at the 12-mo follow-up. CONCLUSION: A greater degree of weight loss, achieved through either a reduced-calorie diet or increased exercise, is associated with increased circulating 25(OH)D concentrations. This trial is registered at clinicaltrials.gov as NCT00470119.

Metabolic considerations in management of surgical patients.

Metabolic changes after surgery, trauma, or serious illness have a complex pathophysiology. The early posttraumatic stress response is physiologic and associated with a state of hyperinflammation, increased oxygen consumption, and increased energy expenditure. These are part of a systemic reaction that encompasses a wide range of endocrinological, immunologic, and hematological effects. Surgery initiates changes in metabolism that can affect virtually all organs and tissues; the metabolic response results in hormone-mediated mobilization of endogenous substrates that leads to stress catabolism. Hypercatabolism has been associated with severe complications related to hyperglycemia, hypoproteinemia, and immunosuppression. Proper metabolic support is essential to restore homeostasis and ensure survival.