Impact of social connectedness on weight loss outcomes in an online program.

Obesity is linked to many negative health consequences. While online behavioral weight loss programs (BWL) are an effective treatment for obesity, weight losses are modest. Social connectedness has been found to improve weight loss outcomes and previous findings suggests that it may be especially important for people of color. The present study investigated the impact of social connectedness (structural connectedness, or network size; relationship quality, and functional connectedness, or social support) on weight loss outcomes in an online BWL program and whether Black race or Hispanic ethnicity moderates the relationship between social connectedness and weight loss. Participants (N = 387) enrolled in a 16-week online BWL program and completed measures of social connectedness before treatment and had their weight measured. Individuals with less structural connectedness (smaller social networks) had greater weight losses. Further, higher levels of functional connectedness (affectionate support, positive support, and relationship quality) mediated the relationship between smaller network size and better weight loss outcomes. Black race / Hispanic ethnicity did not moderate the relationship between social connectedness and weight loss. These findings suggest that the quality of one's relationships, not the size of one's social network, is important for weight loss. Future studies may examine whether online BWL programs that build relationship quality and affectionate and positive support in participants' existing social networks improve overall weight loss outcomes.

Abdominal Obesity Genetic Variants Predict Waist Circumference Regain After Weight Loss.

Although many individuals are able to achieve weight loss, maintaining this loss over time is challenging. We aimed to study whether genetic predisposition to general or abdominal obesity predicts weight regain after weight loss. We examined the associations between genetic risk scores for higher BMI and higher waist-to-hip ratio adjusted for BMI (WHRadjBMI) with changes in weight and waist circumference up to 3 years after a 1-year weight loss program in participants (n = 822 women, n = 593 men) from the Look AHEAD (Action for Health in Diabetes) study who had lost ≥3% of their initial weight. Genetic predisposition to higher BMI or WHRadjBMI was not associated with weight regain after weight loss. However, the WHRadjBMI genetic score did predict an increase in waist circumference independent of weight change. To conclude, a genetic predisposition to higher WHRadjBMI predicts an increase in abdominal obesity after weight loss, whereas genetic predisposition to higher BMI is not predictive of weight regain. These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain. ARTICLE HIGHLIGHTS: Nearly all individuals who intentionally lose weight experience weight regain. Individuals with a higher genetic risk for abdominal adiposity experience increased regain in waist circumference after weight loss. Genetic predisposition to higher BMI does not predict weight regain after weight loss.

Psychological resilience in older adults with type 2 diabetes from the Look AHEAD Trial.

BACKGROUND: There is growing interest in identifying factors associated with healthy aging. This cross-sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). METHODS: Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m2 ) with T2DM enrolled in Look AHEAD (a multi-site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10-year intervention was discontinued. The following items were assessed approximately 14.4 years post-randomization in a cross-sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self-report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF-36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ-9) and mental QOL (SF-36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. RESULTS: Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self-reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self-reported disability and grip strength. CONCLUSIONS: Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross-sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond "loss and decline" to highlight opportunities to facilitate healthy aging.

Uric acid as a predictor of weight gain and cardiometabolic health in the Study of Novel Approaches to Weight Gain Prevention (SNAP) study.

Young adulthood is often a period of substantial weight gain increasing risk for obesity and cardiometabolic disease. Uric acid (UA), a clinical marker of oxidative stress, is associated with cardiometabolic dysfunction in established CVD, type 2 diabetes, and CKD. Yet, few trials have examined UA as a predictor of cardiometabolic risk in young, healthy populations, particularly in the context of weight gain prevention intervention. The purpose of this ancillary study was to examine UA in the Study of Novel Approaches to Weight Gain Prevention (SNAP), a randomized, controlled trial of weight gain prevention strategies in young healthy adults. UA was examined as a predictor of weight and cardiometabolic outcomes over 6 years; the impact of weight gain prevention interventions on UA was also examined. We found that higher baseline UA was a significant predictor of less favorable BMI, triglycerides, HDL, glucose, insulin, and HOMA, independent of age, sex, baseline weight, baseline level of the outcome variable, and weight gain prevention intervention. Additionally, ≥1% weight loss was associated with lower UA. UA is a promising biomarker for future weight gain and cardiometabolic risk in young adults that may respond to weight gain prevention.Clinical trial registration: clinicaltrials.gov identifier NCT01183689.

Impact of COVID-19 on life experiences reported by a diverse cohort of older adults with diabetes and obesity.

OBJECTIVE: This study aimed to measure the impact of the COVID-19 pandemic on self-reported life experiences in older adults with diabetes and obesity. METHODS: Participants were surveyed in 2020 regarding negative and positive impacts of the pandemic across domains of personal, social, and physical experiences. A cumulative negative risk index (a count of all reported negative impacts of 46 items) and a positive risk index (5 items) were characterized in relation to age, sex, race/ethnicity, BMI, and multimorbidity. RESULTS: Response rate was high (2950/3193, 92%), average age was 76 years, 63% were women, and 39% were from underrepresented populations. Women reported more negative impacts than men (6.8 vs. 5.6; p < 0.001 [of 46 items]) as did persons with a greater multimorbidity index (p < 0.001). Participants reporting African American/Black race reported fewer negative impacts than White participants. Women also reported more positive impacts than men (1.9 vs. 1.6; p < 0.001 [of 5 items]). CONCLUSIONS: Older adults with diabetes and obesity reported more positive impacts of the pandemic than negative impacts, relative to the number of positive (or negative) items presented. Some subgroups experienced greater negative impacts (e.g., for women, a greater multimorbidity index). Efforts to reestablish personal, social, and physical health after the pandemic could target certain groups.

Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention: The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (ß = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (ß = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

Changes in the Prevalence of Symptoms of Depression, Loneliness, and Insomnia in U.S. Older Adults With Type 2 Diabetes During the COVID-19 Pandemic: The Look AHEAD Study.

OBJECTIVE: To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020 and to assess risk factors for these conditions including demographics, multimorbidity, BMI, treatment group, and pre-coronavirus 2019 (COVID-19) measure scores. RESEARCH DESIGN AND METHODS: This was a prospective, observational study of participants from the Look AHEAD (Action for Health in Diabetes) cohort study. Data were from two assessments before COVID-19 (visit 1: April 2016-June 2018 and visit 2: February 2018-February 2020) and one assessment during COVID-19 (visit 3: July-December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. RESULTS: The study included 2829 adults (63.2% female, 60.6% White, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (P = 0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3; P < 0.001). Higher odds of mild or greater depressive symptoms at V3 were associated with being female (adjusted odds ratio [OR] 1.4 [95% CI 1.1-1.7]), identifying as non-Hispanic White (OR 1.4 [95% CI 1.1-1.7]), having obesity (OR 1.3 [95% CI 1.0-1.5]), and reporting mild or greater depressive symptoms at V1 (OR 4.0 [95% CI 2.9-5.4]), V2 (OR 4.4 [95% CI 3.2-5.9]), or both visits (OR 13.4 [95% CI 9.7-18.4]). The prevalence of loneliness increased from 12.3% at V1 to 22.1% at V3 (P < 0.001), while the prevalence of insomnia remained stable across visits at 31.5-33.3%. CONCLUSIONS: The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

Does the impact of intensive lifestyle intervention on cognitive function vary depending baseline level of frailty? An ancillary study to the Action for Health in Diabetes (Look AHEAD) Trial.

AIMS: To assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function. METHODS: Standardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles. RESULTS: Worse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI. CONCLUSIONS: Among adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function.

Loneliness Relates to Functional Mobility in Older Adults with Type 2 Diabetes: The Look AHEAD Study.

OBJECTIVE: Little is known about the impact of loneliness on physical health among elderly individuals with diabetes. Here, we examined the relationship of loneliness with disability, objective physical function, and other health outcomes in older individuals with type 2 diabetes and overweight or obesity. METHOD: Data are drawn from the Look AHEAD study, a diverse cohort of individuals (ages 61-92) with overweight or obesity and type 2 diabetes measured 5-6 years after a 10-year weight loss randomized, controlled trial. RESULTS: Loneliness scores were significantly associated with greater disability symptoms and slower 4-meter gait speed (ps < 0.01). Loneliness did not differ across treatment arms. Discussion. Overall, these results extend prior findings relating loneliness to disability and decreased mobility to older individuals with type 2 diabetes and overweight or obesity.

Change in Cardiometabolic Risk Factors Associated With Magnitude of Weight Regain 3 Years After a 1-Year Intensive Lifestyle Intervention in Type 2 Diabetes Mellitus: The Look AHEAD Trial.

Background Weight regain after weight loss is common. The impact on cardiometabolic risk factors is not well established. Methods and Results Publicly available data were analyzed from participants of the Look AHEAD (Action for Health in Diabetes) trial with ≥3% initial weight loss (n=1561) during a 1-year intensive lifestyle intervention and with year 4 follow-up data. Participants who regained (regainers) or maintained (maintainers) weight loss were defined with 5 dichotomized cut points (0%, 25%, 50%, 75%, and 100%) of percentage weight loss regained (weight change from years 1-4 as percentage of first year weight loss). Change in cardiometabolic risk factors after initial weight loss was compared in maintainers and regainers, after controlling for demographics, medications, and baseline and year 1 change in body mass index. The effect was assessed separately in participants with <10% and ≥10% initial weight loss, and women and men. Maintainers exhibited significant improvements to the cardiometabolic risk factors assessed compared with regainers. No weight regain cut point maximized risk difference between maintainers and regainers across risk factors or sex/initial weight loss subgroups. For many risk factors, allowing more regain as part of maintenance (increasing cut point) diminished the cardiometabolic benefit among maintainers. Conclusions Maintaining weight loss was better than regain for all risk factors. No single cut point maximized the risk difference between maintainers and regainers. Maintainers who kept off ≥75% of weight lost had the greatest benefit. These findings emphasize the importance of intervention programs focusing not only on weight loss but weight loss maintenance, given the adverse consequences of the latter. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00017953.

Effects of Cognitive Strategies on Neural Food Cue Reactivity in Adults with Overweight/Obesity.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies of obesity have revealed key roles for reward-related and inhibitory control-related activity in response to food cues. This study examines how cognitive strategies impact neural food cue reactivity. METHODS: In a within-participants, block-design, fMRI paradigm, 30 participants (24 women; mean BMI = 31.8) used four mind-sets while viewing food: "distract" (cognitive behavioral therapy based), "allow" (acceptance and commitment therapy based), "later" (focusing on long-term negative consequences), and "now" (control; focusing on immediate rewards). Participants rated cravings by noting urges to eat on four-point Likert scales after each block. RESULTS: Self-reported cravings significantly differed among all conditions (pairwise comparisons P < 0.05). Cravings were lowest when participants considered long-term consequences (LATER mind-set: 1.7 [SD 0.7]), were significantly higher when participants used the DISTRACT (1.9 [SD 0.7]) and ALLOW (2.3 [SD 0.9]) mind-sets, and were highest when participants used the NOW mind-set (3.2 [SD 0.7]). These behavioral differences were accompanied by differences in neural food cue reactivity. The LATER mind-set (long-term consequences) led to greater inhibitory-control activity in the dorsolateral prefrontal cortex. The cognitive behavioral therapy-based DISTRACT mind-set was associated with greater activity in executive function and reward-processing areas, whereas the ALLOW mind-set (acceptance and commitment therapy) elicited widespread activity in frontal, reward-processing, and default-mode regions. CONCLUSIONS: Because focusing on negative long-term consequences led to the greatest decrease in cravings and increased inhibitory control, this may be a promising treatment strategy for obesity.

Precision behavioral medicine: Implications of genetic and genomic discoveries for behavioral weight loss treatment.

This article reviews the concept of precision behavioral medicine and the progress toward applying genetics and genomics as tools to optimize weight management intervention. We discuss genetic, epigenetic, and genomic markers, as well as interactions between genetics and the environment as they relate to obesity and behavioral weight loss to date. Recommendations for the conditions under which genetics and genomics could be incorporated to support clinical decision-making in behavioral weight loss are outlined and illustrative scenarios of how this approach could improve clinical outcomes are provided. It is concluded that there is not yet sufficient evidence to leverage genetics or genomics to aid the treatment of obesity but the foundations are being laid. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Comparison among criteria to define successful weight-loss maintainers and regainers in the Action for Health in Diabetes (Look AHEAD) and Diabetes Prevention Program trials.

Background: Given the low rates of successful weight maintenance after lifestyle-induced weight loss, it is critical to develop approaches that distinguish successful weight-loss maintainers from regainers.Objective: The aim of this study was to compare published categorization criteria that differentiate maintainers and regainers via quantitative agreement.Design: The study used publicly available data from Look AHEAD (Action for Health in Diabetes; n = 1791) and Diabetes Prevention Program (DPP; n = 613) participants with ≥3% initial weight loss after lifestyle interventions and 4-y follow-up data. Eight previously published criteria defining maintainers and regainers were compared with respect to number of participants and concordance via agreement statistics. Criteria were assessed separately among those with 3-9% and ≥10% initial weight loss.Results: Regainers had higher body weight at year 4 than did maintainers (mean difference range: 6.6-11.9 kg in Look AHEAD; 11.5-14.6 kg in DPP; P < 0.0001). Assessing concordance among criteria, agreement was dependent on initial weight loss. Among those with 3-9% initial weight loss in both cohorts, 9 of 28 comparisons were concordant (agreement ≥80%). Among those with ≥10% initial weight loss, 7 of 28 comparisons in Look AHEAD and 13 of 28 in the DPP were in high agreement. The definition of successful weight-loss maintenance "regaining ≤25% of initial weight loss during maintenance" showed high agreement with the most commonly used definition of "staying ≥10% below initial weight" among those with ≥10% initial weight loss (agreement: 85.0% in Look AHEAD; 87.4% in DPP). The same definition of ≤25% regain showed high agreement with the definition of staying ≥5% below initial weight among those with 3-9% initial weight loss (agreement: 91.6% in Look AHEAD; 90.5% in DPP).Conclusions: Although all of the criteria discriminated on the basis of weight loss, many showed low agreement, which limited cross-study comparisons. Among criteria with high agreement, the definition of successful weight maintenance "regaining ≤25% of initial weight loss during maintenance" is a preferred definition of success, given the realistic challenges of maintaining 100% weight loss and flexible application in populations with high initial weight-loss variations. This trial was registered at clinicaltrials.gov as NCT00017953 (Look AHEAD) and NCT00004992 (DPP).

The Effects of Experimental Manipulation of Sleep Duration on Neural Response to Food Cues.

Despite growing literature on neural food cue responsivity in obesity, little is known about how the brain processes food cues following partial sleep deprivation and whether short sleep leads to changes similar to those observed in obesity. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that short sleep leads to increased reward-related and decreased inhibitory control-related processing of food cues.In a within-subject design, 30 participants (22 female, mean age = 36.7 standard deviation = 10.8 years, body mass index range 20.4-40.7) completed four nights of 6 hours/night time-in-bed (TIB; short sleep) and four nights of 9 hours/night TIB (long sleep) in random counterbalanced order in their home environments. Following each sleep condition, participants completed an fMRI scan while viewing food and nonfood images.A priori region of interest analyses revealed increased activity to food in short versus long sleep in regions of reward processing (eg, nucleus accumbens/putamen) and sensory/motor signaling (ie, right paracentral lobule, an effect that was most pronounced in obese individuals). Contrary to the hypothesis, whole brain analyses indicated greater food cue responsivity during short sleep in an inhibitory control region (right inferior frontal gyrus) and ventral medial prefrontal cortex, which has been implicated in reward coding and decision-making (false discovery rate corrected q = 0.05).These findings suggest that sleep restriction leads to both greater reward and control processing in response to food cues. Future research is needed to understand the dynamic functional connectivity between these regions during short sleep and whether the interplay between these neural processes determines if one succumbs to food temptation.

Identifying the mechanisms through which behavioral weight-loss treatment improves food decision-making in obesity.

OBJECTIVES: Behavioral weight loss (BWL) programs are the recommended treatment for obesity, yet it is unknown whether these programs change one's ability to use self-control in food choices and what specific mechanisms support such change. Using experimental economics methods, we investigated whether changes in dietary behavior in individuals with obesity following BWL are driven by one or more of the following potential mechanisms: changes in the perception of the 1) health or 2) taste of food items, and/or 3) shifting decision weights for health versus taste attributes. Therefore, we compared these mechanisms between obese participants and lifetime normal weight controls (NW) both before and after BWL. METHODS: Females with obesity (N = 37, mean BMI = 33.2) completed a food choice task involving health ratings, taste ratings, and decision-making pre- and post-standard BWL intervention. NW controls (N = 30, BMI = 22.4) completed the same task. RESULTS: Individuals with obesity exhibited increased self-control (selecting healthier, less tasty food choices) post-treatment. However, their rates of self-control remained significantly lower than NW. We found no differences in initial health perceptions across groups, and no changes with treatment. In contrast, taste ratings and the relative value of taste versus health decreased following treatment. Although, post-treatment participants continued to perceive unhealthy foods as tastier and used less self-control than NW controls, they showed significant improvements in these domains following a BWL intervention. CONCLUSIONS: To help individuals improve dietary decisions, additional research is needed to determine how to make greater changes in taste preferences and/or the assignment of value to taste versus health attributes in food choices.

Effect of a Long-Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study.

OBJECTIVES: To assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function. DESIGN: Randomized controlled clinical trial. SETTING: Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Continuation study (U01 DK057136-15). PARTICIPANTS: Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 (N = 3,751). INTERVENTION: Intensive lifestyle intervention (ILI) for weight loss through reduced caloric intake and increased physical activity compared with a control condition of diabetes support and education (DSE). MEASUREMENTS: Certified examiners who were masked to intervention assignment administered a standard battery of cognitive function tests (Modified Mini-Mental State Examination, Rey Auditory Verbal Learning Test, Digit Symbol Coding, Trail-Making Test, Modified Stroop Color-Word Test) to participants 10 to 13 years after enrollment. RESULTS: Assignment to lifestyle intervention was not associated with significantly different overall (P = .10) or domain-specific (all P > .10) cognitive function than assignment to diabetes support and education. Results were fairly consistent across prespecified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI in participants with greater body mass index and in individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness (all P > .05). CONCLUSION: A long-term behavioral weight loss intervention for overweight and obese adults with diabetes mellitus was not associated with cognitive benefit. Trial Registration clinicaltrials.gov Identifier: NCT00017953.

Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program.

OBJECTIVE: Genomewide association studies (GWAS) have identified consistent associations with obesity, with a number of studies implicating eating behavior as a primary mechanism. Few studies have replicated genetic associations with dietary intake. This study evaluates the association between obesity susceptibility loci and dietary intake. METHODS: Data were obtained as part of the Diabetes Prevention Program (DPP), a clinical trial of diabetes prevention in persons at high risk of diabetes. The association of 31 genomewide association studies identified obesity risk alleles with dietary intake, measured through a food frequency questionnaire, was investigated in 3,180 participants from DPP at baseline. RESULTS: The minor allele at BDNF, identified as protective against obesity, was associated with lower total caloric intake (ß = -106.06, SE = 33.13; p = .0014) at experimentwide statistical significance (p = .0016), whereas association of MC4R rs571312 with higher caloric intake reached nominal significance (ß = 61.32, SE = 26.24; p = .0194). Among non-Hispanic white participants, the association of BDNF rs2030323 with total caloric intake was stronger (ß = -151.99, SE = 30.09; p < .0001), and association of FTO rs1421085 with higher caloric intake (ß = 56.72, SE = 20.69; p = .0061) and percentage fat intake (ß = 0.37, SE = 0.08; p = .0418) was also observed. CONCLUSIONS: These results demonstrate with the strength of independent replication that BDNF rs2030323 is associated with 100 to 150 greater total caloric intake per allele, with additional contributions of MC4R and, in non-Hispanic white individuals, FTO. As it has been argued that an additional 100 kcal/d could account for the trends in weight gain, prevention focusing on genetic profiles with high dietary intake may help to quell adverse obesity trends. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov,NCT00004992.

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.

OBJECTIVE:  To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN:  Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES:  Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. RESULTS:  We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. CONCLUSIONS:  We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. SYSTEMATIC REVIEW REGISTRATION:  PROSPERO CRD42015015969.