Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Personalized nutrition: pretreatment glucose metabolism determines individual long-term weight loss responsiveness in individuals with obesity on low-carbohydrate versus low-fat diet.

BACKGROUND/OBJECTIVES: The interaction between fasting plasma glucose (FPG) and fasting insulin (FI) concentrations and diets with different carbohydrate content were studied as prognostic markers of weight loss as recent studies up to 6 months of duration have suggested the importance of these biomarkers. SUBJECTS/METHODS: This was a retrospective analysis of a clinical trial where participants with obesity were randomized to an ad libitum low-carbohydrate diet or a low-fat diet with low energy content (1200-1800 kcal/day [≈ 5.0-7.5 MJ/d]; ≤ 30% calories from fat) for 24 months. Participants were categorized (pretreatment) as normoglycemic (FPG < 5.6 mmol/L) or prediabetic (FPG ≥ 5.6-6.9 mmol/L) and further stratified by median FI. Linear mixed models were used to examine outcomes by FPG and FI values. RESULTS: After 2 years, participants with prediabetes and high FI lost 7.2 kg (95% CI 2.1;12.2, P = 0.005) more with the low-fat than low-carbohydrate diet, whereas those with prediabetes and low FI tended to lose 6.2 kg (95% CI -0.9;13.3, P = 0.088) more on the low-carbohydrate diet than low-fat diet [mean difference: 13.3 kg (95% CI 4.6;22.0, P = 0.003)]. No differences between diets were found among participants with normoglycemia and either high or low FI (both P ≥ 0.16). CONCLUSIONS: Fasting plasma glucose and insulin are strong predictors of the weight loss response to diets with different macronutrient composition and might be a useful approach for personalized weight management.

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

PURPOSE: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. METHODS: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. RESULTS: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. CONCLUSIONS: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.

Should carbohydrate-modified diets be the first option for weight loss in people with impaired glucose metabolism? A scoping review.

While the "precision nutrition" movement is at an early stage of development, several investigations have compared low-fat versus carbohydrate (CHO)-modified diets (i.e., low-or-reduced-CHO, low glycemic index/load diets, and high-fiber) in people with normal versus impaired glucose metabolism. The purpose of this scoping review was to summarize evidence in support of the hypothesis that CHO-modified diets are more effective for weight loss among people with impaired glucose metabolism. Fifteen articles were included in this review: seven retrospective analyses of randomized clinical trials and eight prospective randomized clinical trials with prespecified hypotheses related to a diet (low-fat vs. CHO-modified) × phenotype (normal vs. impaired) interaction. Evidence in support of the hypothesis was identified in six of seven retrospective and three of eight prospective studies, which led to a recommendation of CHO-modified diets as a first-line option for people with impaired glucose metabolism. However, the evidence in support of this recommendation is relatively weak, and dietary prescriptions should consider additional contextual information that may influence overall dietary adherence. Additional and rigorous research using innovative randomized experimental approaches is needed for stronger dietary weight loss recommendations based on pretreatment glycemic status.

Pilot evaluation of a behavioral weight loss program for adults with physical disabilities: State of Slim Everybody usability and feasibility.

Background: People with physical disabilities (PWD) have a higher prevalence of obesity than populations without disability, but most evidence-based weight loss programs have not included this population. The State of Slim (SOS) program is an evidence-based weight loss program that has demonstrated success in producing weight loss in populations without disability, but it has not been adapted for or evaluated in PWD. Methods: The SOS program was systematically adapted using the evidence-informed Guidelines, Recommendations, and Adaptations Including Disability (GRAIDs) framework. A total of 35 participants enrolled in the State of Slim Everybody program. The program was offered entirely online. Body weight, attendance, and food log completion were also tracked weekly. The program length was 16.5 h and included weekly group instruction, with optional one-on-one sessions provided upon request. Following completion, participants completed post-evaluation surveys on overall satisfaction with the program. The primary outcomes were program effectiveness (i.e., body weight), usability, and feasibility. Results: Thirty-two out of 35 participants completed the program, representing a retention rate of 91.4%. Average weight loss was 10.9% (9.9 ± 0.7 kg (t (31) = -13.3, p =< 0.0001)). On a 1 (dissatisfied/completely useless) to 5 (very satisfied/completely helpful) Likert scale, the average score for overall program satisfaction was 4.8 ± 0.1 and program helpfulness 4.6 ± 0.1. Conclusion: The State of Slim Everybody program demonstrated significant weight loss and good usability and feasibility in PWD. Existing adaptation frameworks can be used to create inclusive health promotion programs for adults with physical disabilities.

High- and normal-protein diets improve body composition and glucose control in adults with type 2 diabetes: a randomized trial.

OBJECTIVE: Weight loss of ≥10% improves glucose control and may remit type 2 diabetes (T2D). High-protein (HP) diets are commonly used for weight loss, but whether protein sources, especially red meat, impact weight loss-induced T2D management is unknown. This trial compared an HP diet including beef and a normal-protein (NP) diet without red meat for weight loss, body composition changes, and glucose control in individuals with T2D. METHODS: A total of 106 adults (80 female) with T2D consumed an HP (40% protein) diet with ≥4 weekly servings of lean beef or an NP (21% protein) diet excluding red meat during a 52-week weight loss intervention. Body weight, body composition, and cardiometabolic parameters were measured before and after intervention. RESULTS: Weight loss was not different between the HP (-10.2 ± 1.6 kg) and NP (-12.7 ± 4.8 kg, p = 0.336) groups. Both groups reduced fat mass and increased fat-free mass percent. Hemoglobin A1c, glucose, insulin, insulin resistance, blood pressure, and triglycerides improved, with no differences between groups. CONCLUSIONS: The lack of observed effects of dietary protein and red meat consumption on weight loss and improved cardiometabolic health suggests that achieved weight loss, rather than diet composition, should be the principal target of dietary interventions for T2D management.

Dietary Barriers Appear to Influence the Effects of a Dyadic Web-Based Lifestyle Intervention on Caloric Intake and Adiposity: A Mediation Analysis of the DUET Trial.

Mechanisms that explain behavior change within web-based lifestyle interventions are not well-studied. This secondary analysis explores whether the effects of the DUET web-based lifestyle intervention on diet, physical activity, and/or adiposity are mediated through changes in self-efficacy, social support, and perceived barriers (key constructs of social cognitive theory). Data on mediators, diet quality, caloric intake, moderate-to-vigorous physical activity (MVPA), weight, and waist circumference (WC) were analyzed from 112 cancer survivors and their partners enrolled in the DUET intervention. Mediation analyses were performed using Mplus to execute regression analyses and determine associations. Mediation analyses supported an effect of the intervention on caloric intake (-3.52, 95% CI [-8.08 to -0.84]), weight (-1.60, CI [-3.84 to -0.47]), and WC (-0.83, CI [-1.77 to -0.18]), interpreting these negative associations as intervention induced reductions in dietary barriers. Higher social support was significantly and positively associated with, but not a mediator for, improvements in self-reported and accelerometry-measured MVPA (b = 0.69, CI [0.19, 1.24]) and (b = 0.55, CI [0.15, 1.00]), respectively. Self-efficacy did not appear to mediate the intervention's effects. Findings suggest that the effects of the DUET intervention on diet and adiposity stem from reducing perceived barriers to a healthful, low-calorie diet.

Secondary analysis of a university-based weight loss program in on-campus versus off-campus employees.

Introduction: Many barriers prevent individuals from regularly engaging in physical activity (PA), including lack of time and access to facilities. Providing free gym membership close to one's work may alleviate both time and financial barriers, increase PA, and result in greater weight loss. The purpose of this secondary analysis was to determine if gym usage, self-reported leisure PA, and weight loss differed between participants working on the University of Colorado Anschutz Medical Campus (ON) versus working off-campus (OFF) during a 6-month weight loss trial. Methods: 117 adults (ON, n = 62; OFF, n = 55) with overweight or obesity received free gym memberships for the duration of trial. Average gym check ins/week, self-report leisure PA, weight, and fat and lean mass were compared between groups. Results: ON reported more check-ins than OFF (ON, 0.93 ± 0.16 times/week; OFF, 0.55 ± 0.10 times/week p = 0.038). Both groups reported increased leisure PA, with ON reporting more leisure PA than OFF at month 4. Both groups had reductions in weight and fat mass, which were similar between groups. Conclusion: Gym usage in both groups was low, suggesting that convenient and free gym access only marginally promoted use of provided facilities, likely having little additional impact on PA and weight change. CLINICAL TRIAL REGISTRATION: The parent trial was registered at clinicaltrials.gov: NCT02627105.

Do outcomes from a behavioral weight loss intervention differ in Alabama versus Colorado?

Background: There are well-established regional differences in obesity prevalence in the United States but relatively little is known about why or whether success in weight loss differs regionally. Objective: The objective of this study was to determine whether changes in body weight, engagement in physical activity (PA), and psychosocial factors differed in Alabama (AL) versus Colorado (CO) in response to a 16-week behavioral weight loss program. Design: This is an ancillary study to a weight loss intervention being conducted simultaneously in AL and CO with identical intervention content and delivery in 70 participants (n = 31 AL and n = 39 CO). Body weight, objective (accelerometry) PA, and responses to psychosocial questionnaires (reward-based eating, stress, social support) were collected at baseline and at Week 16. Results: There were no differences in percent weight loss between states (AL: 10.98%; CO: 11.675%, p = 0.70), and weights at Week 16 were not different for participants in AL and CO (AL: 101.54 ± 4.39 kg, CO: 100.42 ± 3.67 kg, p = 0.84). Accelerometry-derived step count, stepping time, and activity score were all greater at Week 16 for participants in AL compared to participants in CO. Hedonic eating scores were more favorable for participants in AL at baseline (AL: 24.08 ± 2.42; CO: 34.99 ± 2.12, p = 0.0023) and at Week 16 (AL: 18.62 ± 2.70; CO: 29.11 ± 2.19, p = 0.0023). Finally, participants in AL presented more favorable social support scores at Week 16 compared to participants in CO. Conclusions: Weight loss did not differ between states, suggesting that factors contributing to higher obesity rates in some regions of the United States may not be barriers to weight loss. Further, participants in AL experienced greater improvements in some factors associated with weight maintenance, indicating the need to study regional differences in weight loss maintenance. National Clinical Trial 03832933.

Weight Change During the Postintervention Follow-up of Look AHEAD.

OBJECTIVE: Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS: These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS: Postintervention weight change averaged -3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10-18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1-8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS: Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

NAMS 2021 Utian Translational Science SymposiumSeptember 2021, Washington, DCCharting the path to health in midlife and beyond: the biology and practice of wellness.

ABSTRACT: Charting the Path to Health in Midlife and Beyond: The Biology and Practice of Wellness was a Translational Science Symposium held on Tuesday, September 21, 2021. Foundational psychosocial and behavioral approaches to promote healthy aging and strategies to disseminate this information were discussed. The following synopsis documents the conversation, describes the state of the science, and outlines a path forward for clinical practice. Wellness, in its broadest sense, prioritizes an orientation toward health, and an embrace of behaviors that will promote it. It involves a journey to improve and maintain physical and mental health and overall well-being to fully engage and live one's best life. It is more about recognizing and optimizing what one can do than what one cannot do and emphasizes the individual's agency over changing what they are able to change. Wellness is therefore not a passive state but rather an active goal to be sought continually. When viewed in this fashion, wellness is accessible to all. The conference addressed multiple aspects of wellness and embraced this philosophy throughout.

Exercise reduces appetite and traffics excess nutrients away from energetically efficient pathways of lipid deposition during the early stages of weight regain.

The impact of regular exercise on energy balance, fuel utilization, and nutrient availability, during weight regain was studied in obese rats, which had lost 17% of their weight by a calorie-restricted, low-fat diet. Weight reduced rats were maintained for 6 wk with and without regular treadmill exercise (1 h/day, 6 days/wk, 15 m/min). In vivo tracers and indirect calorimetry were then used in combination to examine nutrient metabolism during weight maintenance (in energy balance) and during the first day of relapse when allowed to eat ad libitum (relapse). An additional group of relapsing, sedentary rats were provided just enough calories to create the same positive energy imbalance as the relapsing, exercised rats. Exercise attenuated the energy imbalance by 50%, reducing appetite and increasing energy requirements. Expenditure increased beyond the energetic cost of the exercise bout, as exercised rats expended more energy to store the same nutrient excess in sedentary rats with the matched energy imbalance. Compared with sedentary rats with the same energy imbalance, exercised rats exhibited the trafficking of dietary fat toward oxidation and away from storage in adipose tissue, as well as a higher net retention of fuel via de novo lipogenesis in adipose tissue. These metabolic changes in relapse were preceded by an increase in the skeletal muscle expression of genes involved in lipid uptake, mobilization, and oxidation. Our observations reveal a favorable shift in fuel utilization with regular exercise that increases the energetic cost of storing excess nutrients during relapse and alterations in circulating nutrients that may affect appetite. The attenuation of the biological drive to regain weight, involving both central and peripheral aspects of energy homeostasis, may explain, in part, the utility of regular exercise in preventing weight regain after weight loss.

Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial.

BACKGROUND: Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss. OBJECTIVE: To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program. DESIGN: Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936) SETTING: 3 academic medical centers. PATIENTS: 307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)). INTERVENTION: A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d;

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.

Within-Trial Cost-Effectiveness of a Structured Lifestyle Intervention in Adults With Overweight/Obesity and Type 2 Diabetes: Results From the Action for Health in Diabetes (Look AHEAD) Study.

OBJECTIVE: To assess the cost-effectiveness (CE) of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) in adults with overweight/obesity and type 2 diabetes, as implemented in the Action for Health in Diabetes study. RESEARCH DESIGN AND METHODS: Data were from 4,827 participants during their first 9 years of study participation from 2001 to 2012. Information on Health Utilities Index Mark 2 (HUI-2) and HUI-3, Short-Form 6D (SF-6D), and Feeling Thermometer (FT), cost of delivering the interventions, and health expenditures was collected during the study. CE was measured by incremental CE ratios (ICERs) in costs per quality-adjusted life year (QALY). Future costs and QALYs were discounted at 3% annually. Costs were in 2012 U.S. dollars. RESULTS: Over the 9 years studied, the mean cumulative intervention costs and mean cumulative health care expenditures were $11,275 and $64,453 per person for ILI and $887 and $68,174 for DSE. Thus, ILI cost $6,666 more per person than DSE. Additional QALYs gained by ILI were not statistically significant measured by the HUIs and were 0.07 and 0.15, respectively, measured by SF-6D and FT. The ICERs ranged from no health benefit with a higher cost based on HUIs to $96,458/QALY and $43,169/QALY, respectively, based on SF-6D and FT. CONCLUSIONS: Whether ILI was cost-effective over the 9-year period is unclear because different health utility measures led to different conclusions.

Impact of Combined Hormonal Contraceptive Use on Weight Loss: A Secondary Analysis of a Behavioral Weight-Loss Trial.

OBJECTIVE: This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18-month behavioral weight-loss trial. METHODS: Adults (n = 170; 18-55 years; BMI 27-42 kg/m2 ) received a weight-loss intervention that included a reduced-calorie diet, a progressive exercise prescription, and group-based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non-CHC users (non-CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment. RESULTS: At 6 M, weight was reduced from baseline in both CHC (mean, -6.7 kg; 95% CI: -9.8 to -3.7 kg) and non-CHC (-9.1 kg; -9.1 to -6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9 kg), while weight remained relatively unchanged in non-CHC (-0.1 kg; -1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (-1.8 kg; -7.3 to 3.6 kg) and was reduced from baseline in non-CHC (-7.9 kg; -10.2 to -5.5 kg). CONCLUSIONS: In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.

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.

Weight Change 2 Years After Termination of the Intensive Lifestyle Intervention in the Look AHEAD Study.

OBJECTIVE: This study evaluated weight changes after cessation of the 10-year intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. It was hypothesized that ILI participants would be more likely to gain weight during the 2-year observational period following termination of weight-loss-maintenance counseling than would participants in the diabetes support and education (DSE) control group. METHODS: Look AHEAD was a randomized controlled trial that compared the effects of ILI and DSE on cardiovascular morbidity and mortality in participants with overweight/obesity and type 2 diabetes. Look AHEAD was converted to an observational study in September 2012. RESULTS: Two years after the end of the intervention (EOI), ILI and DSE participants lost a mean (SE) of 1.2 (0.2) kg and 1.8 (0.2) kg, respectively (P = 0.003). In addition, 31% of ILI and 23.9% of DSE participants gained ≥ 2% (P < 0.001) of EOI weight, whereas 36.3% and 45.9% of the respective groups lost ≥ 2% of EOI weight (P = 0.001). Two years after the EOI, ILI participants reported greater use of weight-control behaviors than DSE participants. CONCLUSIONS: Both groups lost weight during the 2-year follow-up period, but more ILI than DSE participants gained ≥ 2% of EOI weight. Further understanding is needed of factors that affected long-term weight change in both groups.

History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial.

OBJECTIVE: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). METHODS: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. RESULTS: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group. CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss.

Weight loss is accompanied by several metabolic adaptations that work together to promote rapid, efficient regain. We employed a rodent model of regain to examine the effects of a regular bout of treadmill exercise on these adaptations. Obesity was induced in obesity-prone rats with 16 wk of high-fat feeding and limited physical activity. Obese rats were then weight reduced (approximately 14% of body wt) with a calorie-restricted, low-fat diet and maintained at that reduced weight for 8 wk by providing limited provisions of the diet with (EX) or without (SED) a daily bout of treadmill exercise (15 m/min, 30 min/day, 6 days/wk). Weight regain, energy balance, fuel utilization, adipocyte cellularity, and humoral signals of adiposity were monitored during eight subsequent weeks of ad libitum feeding while the rats maintained their respective regimens of physical activity. Regular exercise decreased the rate of regain early in relapse and lowered the defended body weight. During weight maintenance, regular exercise reduced the biological drive to eat so that it came closer to matching the suppressed level of energy expenditure. The diurnal extremes in fuel preference observed in weight-reduced rats were blunted, since exercise promoted the oxidation of fat during periods of feeding (dark cycle) and promoted the oxidation of carbohydrate (CHO) later in the day during periods of deprivation (light cycle) . At the end of relapse, exercise reestablished the homeostatic steady state between intake and expenditure to defend a lower body weight. Compared with SED rats, relapsed EX rats exhibited a reduced turnover of energy, a lower 24-h oxidation of CHO, fewer adipocytes in abdominal fat pads, and peripheral signals that overestimated their adiposity. These observations indicate that regimented exercise altered several metabolic adaptations to weight reduction in a manner that would coordinately attenuate the propensity to regain lost weight.