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1.  Treatment of Adolescent Obesity Comparing Self-Guided and Group Lifestyle Modification Programs: A Potential Model for Primary Care 
Journal of Pediatric Psychology  2013;38(9):978-986.
Lifestyle modification programs (LMP) for weight loss in adolescents with obesity are effective but not available. Primary care may be a setting for reaching more adolescents. Two models of LMP for use in primary care were examined. Adolescents and caregivers enrolled in a 1-year randomized trial comparing Group LMP with Self-Guided LMP. All participants (N = 169) received the same treatment recommendations and met with a health coach six times in clinic. Group LMP participants had an additional 17 group sessions; those in Self-Guided LMP followed the remainder of the program at home with parental support. The primary outcome was percentage change in initial body mass index. The mean (SE) 1.31% (0.95%) reduction in Group LMP did not differ significantly from the 1.17% (0.99%) decrease in the Self-Guided LMP (p = 0.92). Both treatments were significantly effective in reducing body mass index. Given its brevity, the Self-Guided LMP offers an innovative approach for primary care.
PMCID: PMC3785220  PMID: 23750019
adolescents; obesity; primary care; weight management
2.  Threshold for Improvement in Insulin Sensitivity with Adolescent Weight Loss 
The Journal of pediatrics  2013;163(3):10.1016/j.jpeds.2013.04.003.
To assess the association of weight loss and insulin sensitivity, glucose tolerance, and metabolic syndrome (MS) in obese adolescents following weight loss treatment, and to determine the threshold amount of weight loss required to observe improvements in these measures.
Study design
A randomized, controlled behavioral weight loss trial was conducted with 113 obese adolescents. Changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI), body-mass index (BMI), and MS criteria were assessed at baseline and at month 4.
There was significant improvement in all measures of insulin sensitivity at month 4. Mean fasting insulin dropped to 16.6 from 22.3 μU/mL (p<0.0001). HOMA-IR decreased significantly from 4.9 to 3.7 (p=0.001) and WBISI increased significantly from 2.87 to 3.98 (p<0.0001). An 8% reduction in BMI led to a significant improvement in WBISI (p=0.03) and was the optimal threshold. Fewer individuals met criteria for MS after weight loss (p=0.0038), although there were no significant changes in the individual features of the syndrome.
In this trial, weight loss at month 4 was associated with improved insulin sensitivity in obese adolescents. An approximate decrease in BMI of 8% was the threshold level at which insulin sensitivity improved. As more weight loss programs are designed for obese adolescents, it will be important to have reasonable weight loss goals that will yield improvements in metabolic and cardiovascular disease risk factors.
PMCID: PMC3817268  PMID: 23706362
insulin sensitivity; impaired glucose tolerance; metabolic syndrome; weight loss trial
3.  The Association Between Weight Loss in Caregivers and Adolescents in a Treatment Trial of Adolescents With Obesity 
Journal of Pediatric Psychology  2013;38(7):766-774.
Objective The relationship between weight change in caregivers and their adolescents was evaluated following a randomized trial of lifestyle modification for adolescents, which included either a conventional diet or meal replacements. Methods Adolescents (N = 113) had an M ± SD age of 15.0 ± 1.3 years (62% African American; 26% Caucasian, 12% other; 81% female) and body mass index of 37.1 ± 5.1 kg/m2. Results Mixed effects models yielded a significant association between percentage change in body mass index of caregivers and adolescents from baseline to months 4 and 12 (p = .01). When caregivers lost above the median (−1.67%) at month 4, their adolescents achieved a significantly greater loss at month 12 (−9.1 ± 1.3%) compared with adolescents whose caregivers lost less than the median (−4.3 ± 1.3%) (p = .003). Conclusion Engaging caregivers in their own weight loss efforts during adolescent weight loss treatment may improve adolescent weight loss.
PMCID: PMC3721188  PMID: 23629145
adolescent; behavioral intervention; caregiver; weight loss
4.  Meal Replacements in the Treatment of Adolescent Obesity: A Randomized Controlled Trial 
Obesity (Silver Spring, Md.)  2010;19(6):1193-1199.
The use of meal replacements (MR) in lifestyle modification programs (LMP) for obese adults significantly increases weight loss, compared with the prescription of an isocaloric conventional diet (CD). The present 12-month randomized trial examined 113 obese adolescents (mean [SD] age of 15.0 [1.3] yr and body mass index [BMI] of 37.1 [5.1] kg/m2) who were assigned to a LMP, combined with CD or MR (randomized in 1:2 ratio). For months 1–4, all participants were prescribed 1,300–1500 kcal/d, consumed as a CD or as 3 Slim-Fast® shakes/d and one pre-packaged meal/d (with 5 fruit/vegetable servings/d). After month 4, participants were unmasked to their random assignment of continued use of MR (i.e., MR+MR) or transitioned to CD (i.e., MR+CD). Those initially treated by CD continued with it (i.e., CD). Regression models were used to evaluate percentage change in BMI from baseline to month 4, months 5 to 12, and baseline to month 12. At month 4, participants assigned to MR (N=65) achieved a mean (+SE) 6.3±0.6% reduction in BMI, compared to a significantly (P=0.01) smaller 3.8±0.8% for CD participants (N = 37). From months 5–12, BMI increased significantly (P<0.001) in all three treatment conditions (i.e., MR+MR, MR+CD, and CD), resulting in no significant (P=0.39) differences between groups in percentage change in BMI at month 12. Across groups, mean reduction in BMI from baseline to month 12 was 3.4±0.7% (p<0.01). Use of MR significantly improved short-term weight loss, compared with CD, but its continued use did not improve the maintenance of lost weight.
PMCID: PMC3102147  PMID: 21151016
5.  Maintenance of Weight Loss in Adolescents: Current Status and Future Directions 
Journal of Obesity  2011;2010:789280.
There is a dearth of research on the long-term efficacy and safety of treatments for adolescent obesity. This narrative review examined several approaches to treatment, focusing on long-term effectiveness data in adolescents, as well as relevant findings from studies of adults. The available research suggests that lifestyle modification has promise in obese adolescents, although it is not clear that any particular dietary or physical activity approach is more effective than another. Meal replacements are quite effective in adults and deserve further research in adolescents. Extending the length of treatment to teach weight loss maintenance skills is likely to improve long-term outcomes in adolescents, and delivering treatment via the Internet or telephone is a novel way of doing so. Treatment that combines lifestyle modification with the medication orlistat generally appears to be safe but only marginally superior to lifestyle modification alone. More research is needed on the management of adolescent obesity, which has been overlooked when compared with research on the treatment of obesity in children and adults.
PMCID: PMC3022201  PMID: 21274275
6.  Managing Obesity in Primary Care Practice: An Overview and Perspective from the POWER-UP Study 
Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung, and Blood Institute (NHLBI) in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the Practice-based Opportunities for Weight Reduction (POWER) trials. The present article reviews selected randomized controlled trials, published prior to the initiation of POWER, and then provides a detailed overview of the rationale, methods, and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP’s findings are briefly compared with those from the two other POWER Trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially-available call center, coordinated with an interactive web-site. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services.
PMCID: PMC3786742  PMID: 23921779
weight loss; behavioral weight loss counseling; lifestyle modification; primary care practice; cost-effectiveness
7.  Cost-effectiveness of a Primary Care Intervention to Treat Obesity 
Data on the cost-effectiveness of the behavioral treatment of obesity are not conclusive. The cost-effectiveness of treatment in primary care settings is particularly relevant.
We conducted a within-trial cost-effectiveness analysis of a primary care-based obesity intervention. Study participants were randomized to: Usual Care (quarterly visits with their primary care provider); Brief Lifestyle Counseling (Brief LC; quarterly provider visits plus monthly weight loss counseling visits; or Enhanced Brief Lifestyle Counseling (Enhanced Brief LC; all above interventions, plus choice of meal replacements or weight loss medication). A health care payer perspective was used. Intervention costs were estimated from tracking data obtained prospectively. Quality adjusted life years (QALYs) were estimated with the EuroQol-5D. We estimated cost per kilogram-year of weight loss and cost per QALY.
Weight losses after 2 years were 1.7, 2.9, and 4.6 kg for Usual Care, Brief LC, and Enhanced Brief LC, respectively (p = 0.003 for comparison of Enhanced Brief LC vs. Usual Care). The incremental cost per kilogram-year lost was $292 for Enhanced Brief LC compared to Usual Care (95% CI $38 to $394). The incremental cost per QALY was $115,397, but the 95% CI were undefined. Comparison of short term cost per kg with published estimates of longer term cost per QALYs suggested that the intervention could be cost-effective over the long term (≥ 10 years).
A primary care intervention that included monthly counseling visits and a choice of meal replacements or weight loss medication could be a cost-effective treatment for obesity over the long term. However, additional studies are needed on the cost-effectiveness of behavioral treatment of obesity.
PMCID: PMC3786743  PMID: 23921780
Obesity; Reducing Diet; Primary Care; Costs; Cost-Effectiveness
8.  The Impact of a Primary Care-Based Weight Loss Intervention on Quality of Life 
This study investigated changes in quality of life in men and women who participated in a primary care-based weight loss intervention.
Participants were enrolled in a two-year randomized clinical trial (POWER-UP) conducted at the University of Pennsylvania and six affiliated primary care practices. Inclusion criteria included the presence of obesity (body mass index of 30–50 kg/m2) and at least two components of the metabolic syndrome.
Main Outcome Measures
Quality of life was assessed by three measures: Short Form (12) Health Survey (SF-12); Impact of Weight on Quality of Life-Lite (IWQOL-Lite); and the EuroQol-5D.
Six months after the onset of treatment, and with a mean weight loss of 3.9 ± .30 kg, participants reported significant improvements on all of the measures of interest with the exception of the Mental Component Score of the SF-12. These changes remained significantly improved from baseline at month 24, with the exception of the EuroQol-5D. Many of these improvements were correlated with the magnitude of weight loss and, for the most part, were consistent across gender and race.
Individuals with obesity and components of the metabolic syndrome reported significant improvements in most domains of quality of life with a modest weight loss of 3.7% of initial weight, achieved within the first 6 months of treatment. The majority of these improvements were maintained at month 24, when participants had lost 3.0% of their weight.
PMCID: PMC3786773  PMID: 23921778
quality of life; obesity; lifestyle modification; weight loss
9.  Changes in Eating, Physical Activity, and Related Behaviors in a Primary-Care-Based Weight Loss Intervention 
To examine changes in eating behaviors and physical activity, as well as predictors of weight loss success, in obese adults who participated in a 2-year behavioral weight loss intervention conducted in a primary care setting.
A longitudinal, randomized-controlled, multi-site trial.
390 obese (body mass index, 30 to 50 kg/m2) adults, ≥21 yr, in the Philadelphia region.
Participants were assigned to one of three interventions 1) Usual Care [Quarterly primary care provider (PCP) visits that included education on diet and exercise]; 2) Brief Lifestyle Counseling [quarterly PCP visits plus monthly Lifestyle Counseling (LC) sessions about behavioral weight control]; or 3) Enhanced Brief LC (the previous intervention with a choice of meal replacements or weight loss medication).
At month 24, participants in both Brief LC and Enhanced Brief LC reported significantly greater improvements in mean (±SE) dietary restraint than those in Usual Care (4.4±0.5, 4.8±0.5, and 2.8±0.5, respectively; both ps≤0.016). The percentage of calories from fat, along with fruit and vegetable consumption, did not differ significantly among the three groups. The Brief LC and Enhanced Brief LC groups both reported significantly greater energy expenditure (kcal/week) at month 24 than Usual Care (+593.4±175.9, +415.4±179.6, and −70.4±185.5, respectively; both ps≤0.037). The strongest predictor of weight loss at month 6 (partial R2=33.4%, p<0.0001) and at month 24 (partial R2=19.3%, p<0.001) was food records completed during the first 6 months. Participants who achieved a 5% weight loss at month 6 had 4.7 times greater odds of maintaining a 5% weight loss at month 24.
A behavioral weight loss intervention delivered in a primary care setting can result in significant weight loss, with corresponding improvements in eating restraint and energy expenditure. Moreover, completion of food records, along with weight loss at month 6, is a strong predictor of long-term weight loss.
PMCID: PMC3786775  PMID: 23921776
lifestyle intervention; weight loss; Eating Inventory; food intake; physical activity
10.  Identification of an Obese Eating Style in 4-year-old Children Born at High and Low Risk for Obesity 
Obesity (Silver Spring, Md.)  2009;18(3):505-512.
This study tested whether children’s eating behavior and parental feeding prompts during a laboratory test meal differ among children born at high risk (HR) or low risk (LR) for obesity and are associated with excess child weight gain. At 4 years of age, 32 HR children (mean maternal prepregnancy BMI = 30.4 kg/m2) and 29 LR children (maternal BMI = 19.6 kg/m2) consumed a test meal in which their eating behavior was assessed, including rate of caloric consumption, mouthfuls/min, and requests for food. Parental prompts for the child to eat also were measured at year 4, and child body composition was measured at ages 4 and 6 years. T-tests, and logistic and multiple regression analyses tested study aims. Results indicated that HR and LR children did not differ in eating rate or parental feeding prompts. Greater maternal BMI, child mouthfuls of food/min, and total caloric intake/min during the test meal predicted an increased risk of being overweight or obese at age 6, whereas greater active mealtime was associated with a reduced risk of being overweight or obese. Regression analyses indicated that only mouthfuls of food/min predicted changes in BMI from 4 to 6 years, and mouthfuls of food/min and gender predicted 2-year changes in sum of skinfolds and total body fat. Thus, a rapid eating style, characterized by increased mouthfuls of food/min, may be a behavioral marker for the development of childhood obesity.
PMCID: PMC2917041  PMID: 19779474
11.  The missense variation landscape of FTO, MC4R and TMEM18 in obese children of African ancestry 
Obesity (Silver Spring, Md.)  2013;21(1):159-163.
Common variation at the loci harboring FTO, MC4R and TMEM18 is consistently reported as being statistically the most strongly associated with obesity. We investigated if these loci also harbor rarer missense variants that confer substantially higher risk of common childhood obesity in African American (AA) children. We sequenced the exons of FTO, MC4R and TMEM18 in an initial subset of our cohort i.e. 200 obese (BMI≥95th percentile) and 200 lean AA children (BMI≤5th percentile). Any missense exonic variants that were uncovered went on to be further genotyped in a further 768 obese and 768 lean (BMI≤50th percentile) children of the same ethnicity. A number of exonic variants were observed from our sequencing effort: seven in FTO, of which four were non-synonymous (A163T, G182A, M400V and A405V), thirteen in MC4R, of which six were non-synonymous (V103I, N123S, S136A, F202L, N240S and I251L) and four in TMEM18, of which two were non-synonymous (P2S and V113L). Follow-up genotyping of these missense variants revealed only one significant difference in allele frequency between cases and controls, namely with N240S in MC4R(Fisher's Exact P = 0.0001). In summary, moderately rare missense variants within the FTO, MC4R and TMEM18 genes observed in our study did not confer risk of common childhood obesity in African Americans except for a degree of evidence for one known loss-of-function variant in MC4R.
PMCID: PMC3605748  PMID: 23505181
Obesity; Pediatrics; Genomics
12.  Sleep Architecture and Glucose and Insulin Homeostasis in Obese Adolescents 
Diabetes Care  2011;34(11):2442-2447.
Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis.
This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A1c (HbA1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables.
We found significant U-shaped (quadratic) associations between sleep duration and both HbA1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures.
Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents.
PMCID: PMC3198280  PMID: 21933909
13.  A genome-wide association meta-analysis identifies new childhood obesity loci 
Bradfield, Jonathan P. | Taal, H. Rob | Timpson, Nicholas J. | Scherag, André | Lecoeur, Cecile | Warrington, Nicole M. | Hypponen, Elina | Holst, Claus | Valcarcel, Beatriz | Thiering, Elisabeth | Salem, Rany M. | Schumacher, Fredrick R. | Cousminer, Diana L. | Sleiman, Patrick M.A. | Zhao, Jianhua | Berkowitz, Robert I. | Vimaleswaran, Karani S. | Jarick, Ivonne | Pennell, Craig E. | Evans, David M. | St. Pourcain, Beate | Berry, Diane J. | Mook-Kanamori, Dennis O | Hofman, Albert | Rivadeinera, Fernando | Uitterlinden, André G. | van Duijn, Cornelia M. | van der Valk, Ralf J.P. | de Jongste, Johan C. | Postma, Dirkje S. | Boomsma, Dorret I. | Gauderman, William J. | Hassanein, Mohamed T. | Lindgren, Cecilia M. | Mägi, Reedik | Boreham, Colin A.G. | Neville, Charlotte E. | Moreno, Luis A. | Elliott, Paul | Pouta, Anneli | Hartikainen, Anna-Liisa | Li, Mingyao | Raitakari, Olli | Lehtimäki, Terho | Eriksson, Johan G. | Palotie, Aarno | Dallongeville, Jean | Das, Shikta | Deloukas, Panos | McMahon, George | Ring, Susan M. | Kemp, John P. | Buxton, Jessica L. | Blakemore, Alexandra I.F. | Bustamante, Mariona | Guxens, Mònica | Hirschhorn, Joel N. | Gillman, Matthew W. | Kreiner-Møller, Eskil | Bisgaard, Hans | Gilliland, Frank D. | Heinrich, Joachim | Wheeler, Eleanor | Barroso, Inês | O'Rahilly, Stephen | Meirhaeghe, Aline | Sørensen, Thorkild I.A. | Power, Chris | Palmer, Lyle J. | Hinney, Anke | Widen, Elisabeth | Farooqi, I. Sadaf | McCarthy, Mark I. | Froguel, Philippe | Meyre, David | Hebebrand, Johannes | Jarvelin, Marjo-Riitta | Jaddoe, Vincent W.V. | Smith, George Davey | Hakonarson, Hakon | Grant, Struan F.A.
Nature Genetics  2012;44(5):526-531.
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10−6 in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10−9; OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10−9; OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1.
PMCID: PMC3370100  PMID: 22484627
14.  A Two-Year Randomized Trial of Obesity Treatment in Primary Care Practice 
The New England Journal of Medicine  2011;365(21):1969-1979.
Calls for primary care providers (PCPs) to offer obese patients behavioral weight-loss counseling have not been accompanied by adequate guidance on how such care could be delivered. This randomized trial compared weight loss during a 2-year period in response to three lifestyle interventions, all delivered by PCPs in collaboration with auxiliary health professionals (lifestyle coaches) in their practices.
We randomly assigned 390 obese adults in six primary care practices to one of three types of intervention: usual care, consisting of quarterly PCP visits that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control; or enhanced brief lifestyle counseling, which provided the same care as described for the previous intervention but included meal replacements or weight-loss medication (orlistat or sibutramine), chosen by the participants in consultation with the PCPs, to potentially increase weight loss.
Of the 390 participants, 86% completed the 2-year trial, at which time, the mean (±SE) weight loss with usual care, brief lifestyle counseling, and enhanced brief lifestyle counseling was 1.7±0.7, 2.9±0.7, and 4.6±0.7 kg, respectively. Initial weight decreased at least 5% in 21.5%, 26.0%, and 34.9% of the participants in the three groups, respectively. Enhanced lifestyle counseling was superior to usual care on both these measures of success (P = 0.003 and P = 0.02, respectively), with no other significant differences among the groups. The benefits of enhanced lifestyle counseling remained even after participants given sibutramine were excluded from the analyses. There were no significant differences between the intervention groups in the occurrence of serious adverse events.
Enhanced weight-loss counseling helps about one third of obese patients achieve long-term, clinically meaningful weight loss. (Funded by the National Heart, Lung, and Blood Institute; POWER-UP number, NCT00826774.)
PMCID: PMC3282598  PMID: 22082239
15.  Adolescent eating in the absence of hunger and relation to discretionary calorie allowance 
Eating in the absence of hunger (EAH) is a risk factor for overeating during childhood. The objective of this study was to examine EAH in adolescents based on their familial predisposition to obesity and current weight status. Thirty-one subjects (16 males, 15 females), who were 13 years of age and born at low-risk (LR) or high-risk (HR) for obesity, consumed lunch to fullness. After lunch, subjects had access to different snacks for 15 minutes. EAH referred to energy intake from the snacks. LR females consumed two and a half times more calories from snacks than HR females, and twice as many calories as LR and HR males when expressed as an individualized percentage of daily allowance for discretionary calories. Normal-weight females consumed two and a half times more calories from snacks than obese females and normal-weight males. The association between EAH and weight and obesity risk status depended on adolescents’ sex and could reflect emerging developmental differences, such as dieting or social desirability.
PMCID: PMC3005329  PMID: 21111097
Eating in the absence of hunger; energy intake; discretionary calories; obesity; adolescents
16.  Weight Reduction in Obese Adolescents with and without Binge Eating 
Obesity (Silver Spring, Md.)  2010;19(5):982-987.
Little is known about binge eating (BE) in adolescents. The primary aim of the present study was to examine the relationship between BE and weight loss in adolescents (BMI ≥ 95th percentile) enrolled in a randomized controlled trial of behavioral and pharmacologic treatment of obesity. Participants were 82 treatment-seeking adolescents (BMI = 37.9 ± 3.8 kg/m2; age = 14.1 ± 1.2 years; 67% females; 42% African American, 55% Caucasian). Participants completed the Children’s Depression Inventory, the Piers Harris Self-Esteem Questionnaire, and the Eating Inventory (including cognitive restraint, disinhibition, and hunger scales). BE was assessed by a questionnaire and a confirmatory interview. At baseline, 24% of participants met criteria for BE (N=13 met full BED criteria; N = 7 met sub-threshold BE). There were no significant differences in percentage reduction in initial BMI between participants with or without BE at Month 6 (−7.0 ± 1.6% vs. −6.9 ± 0.9%) or Month 12 (−8.8 ± 2.4% vs. −8.3 ± 1.3%) (omnibus main effect BE p = 0.89, interaction BE*Time p = 0.84, interaction BE*Drug p = 0.61). The rate of BE declined significantly over time from 24% (n=20) at baseline to 8% (n=6) at month 6 and 3% (n=2) at month 12 (p=0.003). There were significant decreases in hunger and disinhibition as well as an increase in cognitive restraint over time (all p ≤ 0.0001). Findings suggest a combination of behavioral and pharmacologic therapy may produce both weight loss and improvement in binge eating.
PMCID: PMC3082597  PMID: 20948512
binge eating; adolescents
17.  Treatment of Comorbid Obesity and Major Depressive Disorder: A Prospective Pilot Study for their Combined Treatment 
Journal of Obesity  2011;2011:870385.
Background. Obese individuals who suffer from major depressive disorder are routinely screened out of weight loss trials. Treatments targeting obesity and depression concurrently have not been tested. Purpose. To test the short-term efficacy of a treatment that combined behavioral weight management and cognitive behavioral therapy (CBT) for obese adults with depression. Methods. Twelve obese females diagnosed with major depressive disorder received weekly group behavioral weight management, combined with CBT for depression, for 16 weeks. Weight, symptoms of depression, and cardiovascular disease (CVD) risk factors were measured at baseline and week 16. Results. Participants lost 11.4% of initial weight and achieved significant improvements in symptoms of depression and CVD risk factors. Conclusions. Obese individuals suffering from major depressive disorder can lose weight and achieve improvements in symptoms of depression and CVD risk factors with 16 weeks of combined treatment. A larger randomized controlled trial is needed to establish the efficacy of this treatment.
PMCID: PMC3136248  PMID: 21773011
18.  Examination of All Type 2 Diabetes GWAS Loci Reveals HHEX-IDE as a Locus Influencing Pediatric BMI 
Diabetes  2009;59(3):751-755.
A number of studies have found that BMI in early life influences the risk of developing type 2 diabetes later in life. Our goal was to investigate if any type 2 diabetes variants uncovered through genome-wide association studies (GWAS) impact BMI in childhood.
Using data from an ongoing GWAS of pediatric BMI in our cohort, we investigated the association of pediatric BMI with 20 single nucleotide polymorphisms at 18 type 2 diabetes loci uncovered through GWAS, consisting of ADAMTS9, CDC123-CAMK1D, CDKAL1, CDKN2A/B, EXT2, FTO, HHEX-IDE, IGF2BP2, the intragenic region on 11p12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and TSPAN8-LGR5. We randomly partitioned our cohort exactly in half in order to have a discovery cohort (n = 3,592) and a replication cohort (n = 3,592).
Our data show that the major type 2 diabetes risk–conferring G allele of rs7923837 at the HHEX-IDE locus was associated with higher pediatric BMI in both the discovery (P = 0.0013 and survived correction for 20 tests) and replication (P = 0.023) sets (combined P = 1.01 × 10−4). Association was not detected with any other known type 2 diabetes loci uncovered to date through GWAS except for the well-established FTO.
Our data show that the same genetic HHEX-IDE variant, which is associated with type 2 diabetes from previous studies, also influences pediatric BMI.
PMCID: PMC2828649  PMID: 19933996
19.  Energy density at a buffet-style lunch differs for adolescents born at high and low risk of obesity 
Eating behaviors  2009;10(4):209-214.
The energy density (ED; kcal/g) of foods, when manipulated in the laboratory, affects short-term energy intake. The aim of this study was to examine if, when given a choice, dietary ED (foods only) and energy intake (expressed as a percentage of subjects’ estimated daily energy requirement) at a self-selected, single meal differs for teens born with a different familial predisposition to obesity and as a function of their sex. Subjects (13 males, 17 females) were 12 years of age and born at high-risk (HR; n = 15) or low-risk (LR; n = 15) for obesity based on maternal pre-pregnancy body mass index (BMI; kg/m2). The buffet meal, served for lunch and consumed ad libitum, consisted of a variety of foods and beverages with a range in ED. HR subjects consumed a more energy-dense meal (foods only) than LR subjects (1.84 vs. 1.42 kcal/g; P = 0.02) and males consumed a more energy-dense meal than females (1.83 vs. 1.43 kcal/g; P = 0.03). Total energy intake, when expressed as a percentage of subjects’ daily EER, did not differ between HR and LR subjects (42% vs. 33%; P = 0.16). Males, compared to females, consumed ∼ 59% more energy from foods and beverages during the meal (46 vs. 29%; P = 0.008). During a single multi-item lunch meal, teens with a familial predisposition to obesity and males, independent of their obesity risk status, self-selected a more energy-dense meal. Familial risk for obesity, through either genetic or environmental pathways, may facilitate a more energy-dense diet.
PMCID: PMC2771780  PMID: 19778749
Energy density; energy intake; buffet lunch; teens
20.  Examination of Type 2 Diabetes Loci Implicates CDKAL1 as a Birth Weight Gene 
Diabetes  2009;58(10):2414-2418.
A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of type 2 diabetes. In order to investigate whether type 2 diabetes risk–conferring alleles associate with low birth weight in our Caucasian childhood cohort, we examined the effects of 20 such loci on this trait.
Using data from an ongoing genome-wide association study in our cohort of 5,465 Caucasian children with recorded birth weights, we investigated the association of the previously reported type 2 diabetes–associated variation at 20 loci including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B, and JAZF1 with birth weight.
Our data show that the minor allele of rs7756992 (P = 8 × 10−5) at the CDKAL1 locus is strongly associated with lower birth weight, whereas a perfect surrogate for variation previously implicated for the trait at the same locus only yielded nominally significant association (P = 0.01; r2 rs7756992 = 0.677). However, association was not detected with any of the other type 2 diabetes loci studied.
We observe association between lower birth weight and type 2 diabetes risk–conferring alleles at the CDKAL1 locus. Our data show that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight.
PMCID: PMC2750235  PMID: 19592620
21.  Beverage Consumption Patterns of Children Born at Different Risk of Obesity 
Obesity (Silver Spring, Md.)  2008;16(8):1802-1808.
Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children.
This study prospectively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity.
Methods and Procedures
Participants were children born at low risk (n = 27) or high risk (n = 22) for obesity based on maternal prepregnancy BMI (kg/m2). Daily beverage consumption was generated from 3-day food records from children aged 3–6 years and coded into seven beverage categories (milk, fruit juice, fruit drinks, caloric and noncaloric soda, soft drinks including and excluding fruit juice). Child anthropometric measures were assessed yearly.
High-risk children consumed a greater percentage of daily calories from beverages at age 3, more fruit juice at ages 3 and 4, more soft drinks (including fruit juice) at ages 3–5, and more soda at age 6 compared to low-risk children. Longitudinal analyses showed that a greater 3-year increase in soda intake was associated with an increased change in waist circumference, whereas a greater increase in milk intake was associated with a reduced change in waist circumference. There was no significant association between change in intake from any of the beverage categories and change in BMI z-score across analyses.
Children’s familial predisposition to obesity may differentially affect their beverage consumption patterns. Future research should examine the extent to which dietary factors may play a role in pediatric body fat deposition over time.
PMCID: PMC2917048  PMID: 18535546
22.  The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature 
BMC Medical Genetics  2010;11:96.
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.
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.
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.
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.
PMCID: PMC2894790  PMID: 20546612
23.  The role of obesity-associated loci identified in genome wide association studies in the determination of pediatric BMI 
Obesity (Silver Spring, Md.)  2009;17(12):2254-2257.
The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. A number of genetic determinants of adult BMI have already been established through genome wide association studies. In this study, we examined 25 single nucleotide polymorphisms (SNPs) corresponding to thirteen previously reported genomic loci in 6,078 children with measures of BMI. Fifteen of these SNPs yielded at least nominally significant association to BMI, representing nine different loci including INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15 and 1q25. Other loci revealed no evidence for association, namely at MTCH2, SH2B1, 12q13 and 3q27. For the 15 associated variants, the genotype score explained 1.12% of the total variation for BMI z-score. We conclude that among thirteen loci that have been reported to associate with adult BMI, at least nine also contribute to the determination of BMI in childhood as demonstrated by their associations in our pediatric cohort.
PMCID: PMC2860782  PMID: 19478790
24.  Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry 
Obesity (Silver Spring, Md.)  2009;17(7):1461-1465.
Recently a modest, but consistently, replicated association was demonstrated between obesity and the single nucleotide polymorphism (SNP), rs17782313, 3’ of the MC4R locus as a consequence of a meta-analysis of genome wide association (GWA) studies of the disease in Caucasian populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European American (EA) obese children (BMI ≥ 95th percentile) and 3,960 EA controls (BMI < 95th percentile), as well as 1,008 African American (AA) obese children and 2,715 AA controls. rs571312, rs10871777 and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054) and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all thirty SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3’ to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in Caucasian children as to their adult Caucasian counterparts but this observation did not extend to African Americans.
PMCID: PMC2860794  PMID: 19265794
25.  Changes in Symptoms of Depression with Weight Loss 
Obesity (Silver Spring, Md.)  2009;17(5):1009-1016.
Recent studies of rimonabant have re-awakened interest in the possible adverse psychiatric effects of weight loss, as well as of weight-loss medications. The present study examined changes in symptoms of depression in 194 obese participants (age = 43.7 ± 10.2 yr; BMI = 37.6 ± 4.1 kg/m2) in a 1-yr randomized trial of lifestyle modification and medication. Participants were assigned to: 1) Sibutramine Alone; 2) Lifestyle Modification Alone; 3) Sibutramine Plus Lifestyle Modification (i.e., Combined Therapy) or; 4) Sibutramine Plus Brief Therapy. Participants completed the Beck Depression Inventory (BDI-II) at baseline and weeks 6, 10, 18, 26, 40 and 52. At 1 yr, participants in Combined Therapy lost the most weight and those in Sibutramine Alone the least (12.1 ± 8.8% vs. 5.5 ± 6.5%; p < 0.01). Mean BDI-II scores across all participants declined from 8.1 ± 6.9 to 6.2 ± 7.7 at 1 yr (p < 0.001), with no significant differences among groups. Despite this favorable change, 13.9% of participants (across the 4 groups) reported potentially discernible increases (5 or more points on the BDI-II) in symptoms of depression at week 52. They lost significantly less weight than participants in the rest of the sample (5.4 ± 7.8% vs. 9.0 ± 7.8%, respectively, p < 0.03). The baseline prevalence of suicidal ideation was 3.6%. Seven new cases of suicidal ideation were observed during the yr, with three in Lifestyle Modification Alone. Further research is needed to identify characteristics of obese patients at risk of negative mood changes (and suicidal ideation) in response to behavioral and pharmacologic therapies.
PMCID: PMC2674126  PMID: 19197266

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