Merel Kozlosky

The FTO gene rs9939609 obesity-risk allele and loss of control over eating

BACKGROUND Children with rs9939609 FTO variant alleles (homozygous = AA and heterozygous = AT) are predisposed to greater adiposity than are those with 2 wild-type alleles (TT). OBJECTIVE Because FTO is highly expressed in hypothalamic regions that are important for appetite, FTO genotype may affect energy balance by influencing eating behavior. Loss of control (LOC) eating, a behavior commonly reported by overweight youth, predicts excessive weight gain in children. However, the relation between FTO genotype and LOC eating has not been previously examined. DESIGN Two-hundred eighty-nine youth aged 6-19 y were genotyped for rs9939609, underwent body-composition measurements, and were interviewed to determine the presence or absence of LOC eating. A subset (n = 190) participated in a lunch buffet test meal designed to model an LOC eating episode. Subjects with AA and AT genotypes were grouped together for comparison with wild-type TT subjects. RESULTS Subjects with at least one A allele (67.7%) had significantly greater body mass indexes, body mass index z scores (P < 0.01), and fat mass (P < 0.05). Of the AA/AT subjects, 34.7% reported LOC compared with 18.2% of the TT subjects (P = 0.002). Although total energy intake at the test meal did not differ significantly by genotype (P = 0.61), AA/AT subjects consumed a greater percentage of energy from fat than did the TT subjects (P < 0.01). CONCLUSIONS Children and adolescents with 1 or 2 FTO rs9939609 obesity-risk alleles report more frequent LOC eating episodes and select foods higher in fat at a buffet meal. Both LOC eating and more frequent selection of energy-dense, palatable foods may be mechanisms through which variant FTO alleles lead to excess body weight.

Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children A Randomized Clinical Trial

OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant. RESEARCH DESIGN AND METHODS This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m2) insulin-resistant children aged 6–12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program. RESULTS Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference −1.09 kg/m2, CI −1.87 to −0.31, P = 0.006), body weight (difference −3.38 kg, CI −5.2 to −1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups −0.07, CI −0.12 to −0.01, P = 0.02), and fat mass (difference −1.40 kg, CI −2.74 to −0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further. CONCLUSIONS Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program.

Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind, Crossover Trial of Liothyronine Versus Levothyroxine

CONTEXT Levothyroxine (L-T(4)) therapy is based on the assumption that the conversion of T(4) into T(3) provides adequate amounts of active hormone at target tissues. However, in rodents, L-T(4) alone does not restore a euthyroid state in all tissues. Previous combination L-T(4)/liothyronine (L-T(3)) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. OBJECTIVE Our objective was to evaluate the efficacy of thyroid hormone replacement with L-T(4) or L-T(3) at doses producing equivalent normalization of TSH. PARTICIPANTS, DESIGN, AND SETTING Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. INTERVENTIONS L-T(3) or L-T(4) were administered thrice daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. MAIN OUTCOME MEASURES Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. RESULTS No difference was observed in TSH between L-T(3) and L-T(4) treatments. L-T(3) resulted in significant weight loss [L-T(4), 70.6 ± 12.5, vs. L-T(3), 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. CONCLUSIONS The substitution of L-T(3) for L-T(4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.

Targeted prevention of excess weight gain and eating disorders in high-risk adolescent girls: a randomized controlled trial

BACKGROUND The high prevalence and incidence of obesity and eating disorders in US adolescent girls are serious health problems. Because of the shared risk factors for obesity and eating disorders, a targeted prevention of both conditions is a priority. OBJECTIVE We determined whether an adapted interpersonal psychotherapy prevention program is more efficacious for reducing excess weight gain and worsening disordered eating than health education in adolescent girls at high risk of obesity and eating disorders. DESIGN A parallel-group, randomized controlled trial was conducted between September 2008 and January 2013 in a university-based laboratory and a federal research hospital. The study included 113 adolescent (12-17-y-old) girls deemed at high risk of adult obesity and eating disorders because of a body mass index (BMI) between the 75th and 97th percentiles and reports of episodes of a loss of control over their eating. Girls were randomly assigned to participate in an adapted interpersonal psychotherapy or a health-education group program for 12 weekly 90-min group sessions. Follow-up assessments occurred immediately after group programs and at 6 and 12 mo. RESULTS Participation in both conditions was associated with decreases in expected BMI gain, age-adjusted BMI metrics, the percentage of fat by using dual-energy X-ray absorptiometry, symptoms of depression and anxiety, and the frequency of loss-of-control eating over 12 mo of follow-up (Ps < 0.001) with no group difference. In follow-up analyses, interpersonal psychotherapy was more efficacious than health education at reducing objective binge eating at the 12-mo follow-up (P < 0.05). CONCLUSIONS The intervention with adolescent girls with loss-of-control eating is associated with lower age-adjusted BMI and percentage of adiposity as well as improved mood symptoms over 1 y. Interpersonal psychotherapy further reduced objective binge eating. Additional research is needed to elucidate the mechanisms by which physical and psychological improvements were observed. This trial was registered at clinicaltrials.gov as NCT00680979.

Latent Profile Analysis to Determine the Typology of Disinhibited Eating Behaviors in Children and Adolescents

OBJECTIVE We used latent profile analysis (LPA) to classify children and adolescents into subtypes based on the overlap of disinhibited eating behaviors-eating in the absence of hunger, emotional eating, and subjective and objective binge eating. METHOD Participants were 411 youths (8-18 years) from the community who reported on their disinhibited eating patterns. A subset (n = 223) ate ad libitum from two test meals. RESULTS LPA produced five subtypes that were most prominently distinguished by objective binge eating (OBE; n = 53), subjective binge eating (SBE; n = 59), emotional eating (EE; n = 62), a mix of emotional eating and eating in the absence of hunger (EE-EAH; n = 172), and no disinhibited eating (No-DE; n = 64). Accounting for age, sex, race, and body mass index z score (BMI-z), the four disinhibited eating groups had more problem behaviors than the no disinhibited eating group (p = .001). OBE and SBE subtypes had greater BMI-z, percent fat mass, disordered eating attitudes, and trait anxiety than EE, EE-EAH, and No-DE subtypes (ps < .01). However, the OBE subtype reported the highest eating concern (p < .001), and the OBE, SBE, and EE subtypes reported higher depressive symptoms than the EE-EAH and No-DE subtypes. Across both test meals, OBE and SBE subtypes consumed a lesser percentage of protein and a higher percentage of carbohydrate than the other subtypes (ps < .02), adjusting for age, sex, race, height, lean mass, percent fat mass, and total intake. EE subtypes also consumed a greater percentage of carbohydrate and a lower percentage of fat than the EE-EAH and No-DE subtypes (ps < .03). The SBE subtype consumed the least total calories (p = .01). DISCUSSION We conclude that behavioral subtypes of disinhibited eating may be distinguished by psychological characteristics and objective eating behavior. Prospective data are required to determine whether subtypes predict the onset of eating disorders and obesity.

Pre-meal affective state and laboratory test meal intake in adolescent girls with loss of control eating

Loss of control eating confers risk for excess weight gain and exacerbated disordered eating. Affect theory proposes that loss of control eating is used to cope with negative mood states. Self-report data suggest that negative affect may contribute to the etiology of loss of control eating, but this theory has not been well-tested using laboratory paradigms. We examined associations between pre-meal affective states and intake during a laboratory test meal. One-hundred and ten adolescent girls with reported loss of control eating whose body mass index fell between the 75th and 97th percentile for age and sex completed state mood ratings prior to a test-meal. Results indicated that pre-meal state negative affect was associated with greater carbohydrate and less protein consumption, as well as greater snack and dessert and less fruit and dairy intake. All girls experienced significant decreases in negative affect from pre- to post-meal, but intake during the meal was unassociated with post-meal affect. In support of affect theory, negative affective states reported among girls with loss of control may be a driving factor for increased energy-dense food intake, which may play a role in excess weight gain.

Insulin Resistance, Hyperinsulinemia, and Energy Intake in Overweight Children

OBJECTIVE To examine the relationship between energy intake during a buffet meal and indexes of insulin dynamics in overweight children. STUDY DESIGN Ninety-five nondiabetic, overweight (body mass index > or = 95th percentile) children (age 10.3 +/- 1.4 years) selected lunch from a 9835-kcal buffet eaten ad libitum after an overnight fast. The associations between energy intake and measures of insulin dynamics, in the postabsorptive state and during a 2-hour hyperglycemic clamp, were determined. Covariates in the statistical model included race, sex, skeletal age, fat-free mass, fat mass, socioeconomic status, and number of foods in the buffet rated as acceptable. RESULTS Energy intake was positively associated with the fasting homeostasis model assessment for insulin resistance index (beta = 0.24, P = .042), fasting insulin/glucose ratio (beta = 0.24, P = .044), first-phase insulin (beta = 0.23, P = .032), and first-phase C-peptide (beta = 0.21, P = .046); energy intake was negatively associated with clamp-derived insulin sensitivity (beta = -0.29, P = .042). Each 10% decrease in clamp-derived insulin sensitivity predicted a 27-kcal greater energy intake. CONCLUSIONS Insulin resistance and hyperinsulinemia are associated with greater energy intake after an overnight fast in overweight children. These associations suggest mechanisms whereby insulin resistance may contribute to excessive weight gain in children.

Effects of metformin on energy intake and satiety in obese children

To investigate the effects of metformin on appetite and energy intake in obese children with hyperinsulinaemia.

Self‐efficacy beliefs and eating behavior in adolescent girls at‐risk for excess weight gain and binge eating disorder

OBJECTIVE To examine the relationship between self-related agency beliefs and observed eating behavior in adolescent girls with loss of control (LOC) eating. METHOD One-hundred eleven adolescent girls (14.5 ± 1.7 years; BMI: 27.1 ± 2.6 kg/m(2)) were administered the General Self-Efficacy Scale and the Weight Efficacy Lifestyle Questionnaire (WEL). Adolescents then participated in a laboratory test meal. RESULTS Greater general and eating self-efficacy were associated with fewer episodes of LOC eating. General self-efficacy was inversely related to total intake at the meal (p < .01). Only the WEL availability subscale score, but not the other WEL subscales, was inversely related to total energy, snack, and dessert intake (ps < 0.05). DISCUSSION General self-related agency beliefs may be important in relation to energy consumption. Among girls susceptible to disordered eating and obesity, the domain-specific belief in ones ability to refrain from eating when food is widely available may be especially salient in determining overeating in the current food environment. Further research is therefore needed to assess the predictive validity of these beliefs on eating and weight outcomes.

Construct validity of the Emotional Eating Scale Adapted for Children and Adolescents

Background:Emotional eating, defined as eating in response to a range of negative emotions, is common in youths. Yet, there are few easily administered and well-validated methods to assess emotional eating in pediatric populations.Objective:The current study tested the construct validity of the Emotional Eating Scale (EES) Adapted for Children and Adolescents (EES-C) by examining its relationship to observed emotional eating at laboratory test meals.Method:A total of 151 youths (8–18 years) participated in two multi-item lunch buffet meals on separate days. They ate ad libitum after being instructed to ‘eat as much as you would at a normal meal’ or to ‘let yourself go and eat as much as you want’. State negative affect was assessed immediately before each meal. The EES-C was completed 3 months, on average, before the first test meal.Results:Among youths with high EES-C total scores, but not low EES-C scores, higher pre-meal state negative affect was related to greater total energy intake at both meals, with and without the inclusion of age, race, sex and body mass index (BMI) standard deviation as covariates (ps<0.03).Discussion:The EES-C demonstrates good construct validity for children and adolescents’ observed energy intake across laboratory test meals designed to capture both normal and disinhibited eating. Future research is required to evaluate the construct validity of the EES-C in the natural environment and the predictive validity of the EES-C longitudinally.