A Systematic Review of Genetic Correlates of Weight Loss After Bariatric Surgery.

This systematic review synthesized research evaluating the relationship between genetic predictors and weight loss after bariatric surgery. Fifty-seven studies were identified that examined single genes or genetic risk scores. Uncoupling protein (UCP) rs660339 was associated with excess weight loss after surgery in 4 of 6 studies. The most commonly assessed genes were fat mass and obesity-associated (FTO) gene (n = 10) and melanocortin-4 receptor (MC4R) (n = 14). Both were inconsistently related to weight loss. Genetic risk scores predicted weight loss in 6 of 7 studies. This evidence suggests the potential of using genetic variants and genetic risk scores to predict the amount of weight loss anticipated after bariatric surgery and identify patients who may be at risk for suboptimal weight reduction.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

Causal Attributions for Obesity Among Patients Seeking Surgical Versus Behavioral/Pharmacological Weight Loss Treatment.

Obesity is frequently attributed to causes such as laziness and lack of willpower and personal responsibility. The current study identified causal attributions for obesity among patients seeking bariatric surgery and compared them to those among patients seeking less invasive weight loss treatment (behavioral/pharmacological). The 16-item Causal Attributions for Obesity scale (CAO; rated 1-7) was administered to 102 patients seeking bariatric surgery (sample 1) and 178 patients seeking behavioral/pharmacological weight loss treatment (sample 2). Between-subjects analyses compared CAO ratings for the two samples. Results showed that behavioral factors were the highest-rated attributions in both samples. Sample 1 had higher ratings of biological and environmental factors than did sample 2. Overall, patients seeking bariatric surgery had a more complex conceptualization of obesity than did patients seeking behavioral/pharmacological treatment. TRIAL REGISTRATION: NCT02388568.

Effects of obesity therapies on sleep disorders.

Obesity is a significant risk factor for obstructive sleep apnea syndrome (OSAS), and has also been linked to reductions in sleep quality and quantity. Weight loss has been shown to be an effective treatment for improving OSAS; however, there is a high degree of variability in improvements of OSAS in response to weight loss. There are three modalities of obesity therapies: 1) lifestyle modification, which includes changes in dietary intake and physical activity, along with behavioral interventions; 2) pharmacologic agents; and 3) bariatric surgery. Individuals have a highly variable response to the various obesity interventions, and maintenance of weight loss can be especially challenging. These factors influence the effect of weight loss on sleep disorders. There is still a need for large, well-controlled studies examining short- and long-term efficacy of weight loss modalities and their impact on long-term treatment of OSAS and other sleep parameters, particularly in youth. Nonetheless, given our current knowledge, weight reduction should always be encouraged for people coping with obesity, OSAS, and/or sleep disruptions and resources identified to assist patients in choosing a weight loss approach that will benefit them the most.

Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study.

Background: Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention (ILI) on physical function were assessed using a randomized post-test design in the Look AHEAD trial. Methods: Overweight and obese (body mass index ≥ 25 kg/m2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years postrandomization and 1.5 years after the intervention was stopped (n = 3,783). Results: Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019 [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001, respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older versus younger participants (0.081 [0.038 to 0.124] vs 0.013 [-0.021 to 0.047], p = .01). Conclusions: An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes. ClinicalTrials.gov Identifier: NCT00017953.

Group cognitive-behavioral treatment for internalized weight stigma: a pilot study.

OBJECTIVE: This study tested a novel group-based, cognitive-behavioral intervention designed to reduce internalized weight stigma among individuals with obesity. METHODS: A total of eight men and women with obesity who had experienced weight stigma and reported high levels of internalized weight stigma attended the Weight Bias Internalization and Stigma (BIAS) Program. The program provided eight weekly sessions of cognitive-behavioral treatment to cope with weight stigma. Participants completed questionnaires pre- and post-intervention, including the Weight Bias Internalization Scale (WBIS), Fat Phobia Scale, Weight Efficacy Life-Style Questionnaire (WEL), and Beck Depression Inventory-II (BDI-II). Six additional participants were included in a quasi-control group that received no intervention until after completing all study measures. RESULTS: Participants in the Weight BIAS Program reported significantly greater decreases in WBIS and Fat Phobia scores, and greater increases in WEL scores than participants in the quasi-control group (ps < .04). Changes in BDI-II scores did not differ between groups. Treatment-acceptability ratings were high among participants who received the intervention. CONCLUSION: Including cognitive-behavioral strategies to address weight stigma in weight management programs could potentially reduce internalized weight stigma and enhance treatment outcomes.

Changes in Dietary Intake and Eating Behavior in Adolescents After Bariatric Surgery: an Ancillary Study to the Teen-LABS Consortium.

BACKGROUND: A growing number of studies suggest that bariatric surgery is safe and effective for adolescents with severe obesity. However, surprisingly little is known about changes in dietary intake and eating behavior of adolescents who undergo bariatric surgery. OBJECTIVE: Investigate changes in dietary intake and eating behavior of adolescents with obesity who underwent bariatric surgery (n = 119) or lifestyle modification (LM) (n = 169). SETTING: University-based health systems METHODS: A prospective investigation of 288 participants (219 female and 69 male) prior to bariatric surgery or LM and again 6, 12, and 24 months (surgery patients only) after treatment. Measures included changes in weight, macronutrient intake, eating behavior, and relevant demographic and physiological variables. RESULTS: Adolescents who underwent bariatric surgery experienced significantly greater weight loss than those who received LM. The two groups differed in self-reported intake of a number of macronutrients at 6 and 12 months from baseline, but not total caloric intake. Patients treated with surgery, compared to those treated with LM, also reported significantly greater reductions in a number of disordered eating symptoms. After bariatric surgery, greater weight loss from postoperative month 6 to 12 was associated with self-reported weight consciousness, craving for sweets, and consumption of zinc. CONCLUSIONS: Adolescents who underwent bariatric surgery, compared to those who received LM, reported significantly greater reductions in weight after 1 year. They also reported greater reductions in disordered eating symptoms. These findings provide new information on changes in dietary intake and eating behavior among adolescents who undergo bariatric surgery.

An open-label efficacy trial of escitalopram for night eating syndrome.

OBJECTIVE: Night eating syndrome (NES) has become increasingly recognized as a disorder in need of effective treatments. Selective serotonin reuptake inhibitors have shown efficacy in previous trials, so we sought to expand our understanding of the efficacy of escitalopram in the current trial. METHOD: Thirty-one adults with NES participated in a 12-week open-label trial of escitalopram. Outcome measures included the Night Eating Symptom Scale (NESS), percent of daily intake after the evening meal (% intake) and number of nocturnal ingestions/week (NI), weight, total awakenings/week, mood, and quality of life. Mixed-effects models were used to assess change over time. RESULTS: Significant reductions were observed from week 0 to week 12 for the NESS (30.2 to 15.2), % intake (46% to 17%), NI (5.8 to 1.2), weight (90.2 to 88.6 kg), awakenings (8.1 to 2.7), and BDI-II (12.1 to 7.7). Outcomes did not differ significantly by gender, age, race, or psychiatric co-morbidity status. Eighteen of 31 completed 12 weeks of treatment. DISCUSSION: This open-label trial of escitalopram showed significant reductions in symptoms associated with NES. Randomized controlled trials are warranted to test these findings. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01401595.

Maternal obesity associated with inflammation in their children.

BACKGROUND: This study explored the association between maternal obesity during pregnancy and the inflammatory markers, tumor necrosis factor-α, interleukin-6 and high sensitivity C-reactive protein (hs-CRP), and the cytokine, adiponectin, in the offspring. METHODS: Weight, height, Tanner stage and biomarkers were measured in thirty-four 12-year-old children, from the Infant Growth Study, who were divided into high risk (HR) and low risk (LR) groups based on maternal pre-pregnancy body mass index (BMI). RESULTS: The two groups differed markedly in their hs-CRP levels, but no group difference was found for the other three biomarkers. The odds ratio (OR) of HR children having detectable hs-CRP levels was 16 times greater than that of LR children after adjusting for confounding variables, including BMI z-score, Tanner stages and gender (OR: 16; 95% CI: 2-123). CONCLUSIONS: These results suggest that maternal obesity during pregnancy is associated with later development of elevated hs-CRP in the offspring, even after controlling for weight.

Obesity, psychiatric status, and psychiatric medications.

This article has shown that obesity is related to several psychiatric disorders, the most thoroughly researched of which is depression. In both community and clinical populations, the observed relationship is more consistent in women than in men, and is stronger in more severely obese individuals. The presence of BED also is associated with elevated risk of additional psychopathology. Longitudinal research provides evidence to support a pathway from obesity to depression, as well as one from depression to obesity. Weight loss, particularly with nonpharmacologic methods, appears to have favorable group-level effects on mood, but may be associated with adverse outcomes for some individuals. Persons who require antipsychotic medications are at risk for weight gain and metabolic abnormalities, and their management should be informed by consensus guidelines.

The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.

BACKGROUND: Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies. METHODS: To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort. RESULTS: Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score. CONCLUSION: Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.

Metabolic syndrome and health-related quality of life in obese individuals seeking weight reduction.

BACKGROUND: No previous research has examined the association between metabolic syndrome (MetSyn) and health-related quality of life (HRQoL) using standard criteria for defining MetSyn. We hypothesized that MetSyn would be associated with lower HRQoL on measures of physical and mental health. METHODS AND PROCEDURES: Participants were 361 individuals in two randomized weight loss trials. MetSyn was defined by the National Cholesterol Education Panel criteria. The Medical Outcomes Study, Short Form-36 (SF-36) was used to assess HRQoL. Differences in HRQoL and in clinical and psychosocial characteristics were compared among participants with and without MetSyn. Multiple regression was used to determine predictors of HRQoL. RESULTS: MetSyn was associated with lower scores on the physical function and general health subscales of the SF-36 and on the physical component summary (PCS) score. This association remained after controlling for age or depression but was eliminated by controlling for BMI. MetSyn was not associated with lower mental quality of life, a higher depression score, tobacco or alcohol use, or a higher rate of psychosocial stressors. DISCUSSION: Individuals with MetSyn reported lower HRQoL. This appeared to be an effect of increased weight, rather than a unique effect of MetSyn. Larger studies are needed to assess whether MetSyn may have an independent effect on HRQoL.

The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it.

The Look AHEAD (Action for Health in Diabetes) study is a multicenter, randomized controlled trial designed to determine whether intentional weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. The study began in 2001 and is scheduled to conclude in 2012. A total of 5145 participants have been randomly assigned to a lifestyle intervention or to an enhanced usual care condition (i.e., diabetes support and education). This article describes the lifestyle intervention and the empirical evidence to support it. The two principal intervention goals are to induce a mean loss >or = 7% of initial weight and to increase participants' moderately intense physical activity to > or =175 min/wk. For the first 6 months, participants attend one individual and three group sessions per month and are encouraged to replace two meals and one snack a day with liquid shakes and meal bars. From months 7 to 12, they attend one individual and two group meetings per month and continue to replace one meal per day (which is recommended for the study's duration). Starting at month 7, more intensive behavioral interventions and weight loss medication are available from a toolbox, designed to help participants with limited weight loss. In Years 2 to 4, treatment is provided mainly on an individual basis and includes at least one on-site visit per month and a second contact by telephone, mail, or e-mail. After Year 4, participants are offered monthly individual visits. The intervention is delivered by a multidisciplinary team that includes medical staff who monitor participants at risk of hypoglycemic episodes.

Randomized trial of lifestyle modification and pharmacotherapy for obesity.

BACKGROUND: Weight-loss medications are recommended as an adjunct to a comprehensive program of diet, exercise, and behavior therapy but are typically prescribed with minimal or no lifestyle modification. This practice is likely to limit therapeutic benefits. METHODS: In this one-year trial, we randomly assigned 224 obese adults to receive 15 mg of sibutramine per day alone, delivered by a primary care provider in eight visits of 10 to 15 minutes each; lifestyle-modification counseling alone, delivered in 30 group sessions; sibutramine plus 30 group sessions of lifestyle-modification counseling (i.e., combined therapy); or sibutramine plus brief lifestyle-modification counseling delivered by a primary care provider in eight visits of 10 to 15 minutes each. All subjects were prescribed a diet of 1200 to 1500 kcal per day and the same exercise regimen. RESULTS: At one year, subjects who received combined therapy lost a mean (+/-SD) of 12.1+/-9.8 kg, whereas those receiving sibutramine alone lost 5.0+/-7.4 kg, those treated by lifestyle modification alone lost 6.7+/-7.9 kg, and those receiving sibutramine plus brief therapy lost 7.5+/-8.0 kg (P<0.001). Those in the combined-therapy group who frequently recorded their food intake lost more weight than those who did so infrequently (18.1+/-9.8 kg vs. 7.7+/-7.5 kg, P=0.04). CONCLUSIONS: The combination of medication and group lifestyle modification resulted in more weight loss than either medication or lifestyle modification alone. The results underscore the importance of prescribing weight-loss medications in combination with, rather than in lieu of, lifestyle modification.