Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience.

BACKGROUND: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy. OBJECTIVES: We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms. METHODS: The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11-17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time. RESULTS: Lifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months. CONCLUSIONS: Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.

Hypoxia Induces a Prothrombotic State Independently of the Physical Activity.

Hypoxia (oxygen deprivation) is known to be associated with deep vein thrombosis and venous thromboembolism. We attempted to get a better comprehension of its mechanism by going to high altitude, thereby including the potential contributing role of physical activity. Two groups of 15 healthy individuals were exposed to hypoxia by going to an altitude of 3900 meters, either by climbing actively (active group) or transported passively by cable car (passive group). Both groups were tested for plasma fibrinogen, von Willebrand factor and factor VIII levels, fibrinolysis, thrombin generating capacity, heart rate, oxygen saturation levels and blood pressure. As a control for the passive group, 7 healthy volunteers stayed immobile in bed for 7 days at normoxic conditions. The heart rate increased and oxygen saturation levels decreased with increasing altitude. Fibrinolysis and fibrinogen levels were not affected. Factor VIII and von Willebrand factor levels levels increased significantly in the active group, but not in the passive group. Plasma thrombin generation remained unchanged in both the active and passive group with increasing altitude and during 7 days of immobility in healthy subjects. However, by applying whole blood thrombin generation, we found an increased peak height and endogenous thrombin potential, and a decreased lagtime and time-to-peak with increasing levels of hypoxia in both groups. In conclusion, by applying whole blood thrombin generation we demonstrated that hypoxia causes a prothrombotic state. As thrombin generation in plasma did not increase, our results suggest that the cellular part of the blood is involved in the prothrombotic phenotype induced by hypoxia.

Cardio-metabolic risk screening among adolescents: understanding the utility of body mass index, waist circumference and waist to height ratio.

BACKGROUND: Few studies have assessed how well body mass index (BMI), waist circumference (WC), or waist to height ratio (WtHR) perform in identifying cardio-metabolic risk among youth. OBJECTIVE: The objective of this study was to evaluate the utility of BMI and WC percentiles and WtHR to distinguish adolescents with and without cardio-metabolic risk. METHODS: A cross-sectional analysis of data from 6097 adolescents aged 10-13 years who participated in the HEALTHY study was conducted. Receiver operating characteristic curves determined the discriminatory ability of BMI and WC percentiles and WtHR. RESULTS: The discriminatory ability of BMI percentile was good (area under the curve [AUC] ≥ 0.80) for elevated insulin and clustering of ≥3 risk factors, with optimal cut-points of 96 and 95, respectively. BMI percentile performed poor to fair (AUC = 0.57-0.75) in identifying youth with the majority of individual risk factors examined (elevated glucose, total cholesterol, low-density lipoprotein, blood pressure, triglycerides and high-density lipoprotein). WC percentile and WtHR performed similarly to BMI percentile. CONCLUSIONS: The current definition of obesity among US children performs well at identifying adolescents with elevated insulin and a clustering of ≥3 cardio-metabolic risk factors. Evidence does not support WC percentile or WtHR as superior screening tools compared with BMI percentile for identifying cardio-metabolic risk.

Preoperative lifestyle intervention in bariatric surgery: initial results from a randomized, controlled trial.

OBJECTIVE: To document preoperative outcomes of a behavioral lifestyle intervention delivered to patients prior to bariatric surgery in comparison to treatment as usual (insurance-mandated physician supervised diet). DESIGN AND METHODS: After completing a baseline assessment, candidates for surgery were randomized to a 6-month, evidence-informed, manualized lifestyle intervention (LIFESTYLE, n = 121) or to preoperative care as usual (USUAL CARE, n = 119). At 6 months, 187 participants remained candidates for bariatric surgery and were included in the analyses. RESULTS: LIFESTYLE participants lost significantly more weight than those receiving USUAL CARE [8.3 ± 7.8 kg vs. 3.3 ± 5.5 kg, F(1,183) = 23.6, P < 0.0001], with an effect size of 0.72. Additionally, logistic regression modeling indicated that LIFESTYLE patients were significantly more likely to lose at least 5% of initial body weight than those in USUAL CARE [OR (95% CI) = 2.94 (1.253, 6.903)], as were participants who were heavier [OR (95% CI) = 1.07 (1.001-1.14) for each unit increase in BMI] or with larger improvements in eating behaviors [OR (95% CI) = 1.1 (1.049, 1.145) for each unit increase on the Eating Behavior Inventory). CONCLUSIONS: A behavioral lifestyle intervention for severely overweight individuals leads to clinically significant weight loss prior to bariatric surgery. Post-surgery follow-up will allow us to examine the impact of the preoperative intervention on postoperative outcomes.

Classification of eating disturbance in children and adolescents: proposed changes for the DSM-V.

Childhood and adolescence are critical periods of neural development and physical growth. The malnutrition and related medical complications resulting from eating disorders such as anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified may have more severe and potentially more protracted consequences during youth than during other age periods. The consensus opinion of an international workgroup of experts on the diagnosis and treatment of child and adolescent eating disorders is that (a) lower and more developmentally sensitive thresholds of symptom severity (e.g. lower frequency of purging behaviours, significant deviations from growth curves as indicators of clinical severity) be used as diagnostic boundaries for children and adolescents, (b) behavioural indicators of psychological features of eating disorders be considered even in the absence of direct self-report of such symptoms and (c) multiple informants (e.g. parents) be used to ascertain symptom profiles. Collectively, these recommendations will permit earlier identification and intervention to prevent the exacerbation of eating disorder symptoms.

Self-reported binge eating in severe pediatric obesity: impact on weight change in a randomized controlled trial of family-based treatment.

OBJECTIVE: This study sought to document self-reported binge eating in a large sample of severely obese children and to examine the impact of binge eating on changes in percent overweight among children randomized to family-based behavioral treatment (intervention) versus control (usual care). PARTICIPANTS AND METHODS: As part of a larger randomized controlled trial, 192 children aged 8-12 years (M=10.2, s.d.=1.2) with a mean body mass index (BMI) percentile of 99.2 (s.d.=0.7) completed assessments at baseline and 6-, 12-, and 18 months post-randomization. A parent or guardian also participated. Child psychological symptoms, including binge eating, were measured before randomization using self-report questionnaires. Child height and weight were measured at baseline, 6-, 12-, and 18 months. The primary study outcome was percent overweight (that is, percent over median BMI for age and sex). RESULTS: Twenty-two children (11.5%) endorsed binge eating at baseline (Binge Eating Group). Children in the Binge Eating Group were younger and had more depressive, anxiety, and eating disorder symptoms, and lower self-esteem than children in the rest of the sample (No Binge Eating Group). There also were differences between the Binge Eating and No Binge Eating groups with respect to the short-term effects of treatment group assignment on change in percent overweight during the study. Specifically, improvements in percent overweight in the intervention condition relative to usual care were documented in the No Binge Eating Group only. Among children in the Binge Eating Group, those assigned to intervention showed a 2.6% increase in percent overweight, on average, at the completion of acute treatment as compared to an 8.5% decrease among children without binge eating. However, these effects were not maintained during follow-up. CONCLUSION: Results of this study suggest the importance of considering binge eating in the development of weight management programs for severely obese youth.

Rationale, design and methods of the HEALTHY study behavior intervention component.

HEALTHY was a multi-center primary prevention trial designed to reduce risk factors for type 2 diabetes in adolescents. Seven centers each recruited six middle schools that were randomized to either intervention or control. The HEALTHY intervention integrated multiple components in nutrition, physical education, behavior change and communications and promotion. The conceptual rationale as well as the design and development of the behavior intervention component are described. Pilot study data informed the development of the behavior intervention component. Principles of social learning and health-related behavior change were incorporated. One element of the behavior intervention component was a sequence of peer-led, teacher-facilitated learning activities known as FLASH (Fun Learning Activities for Student Health). Five FLASH modules were implemented over five semesters of the HEALTHY study, with the first module delivered in the second semester of the sixth grade and the last module in the second semester of the eighth grade. Each module contained sessions that were designed to be delivered on a weekly basis to foster self-awareness, knowledge, decision-making skills and peer involvement for health behavior change. FLASH behavioral practice incorporated individual and group self-monitoring challenges for eating and activity. Another element of the behavior intervention component was the family outreach strategy for extending changes in physical activity and healthy eating beyond the school day and for supporting the student's lifestyle change choices. Family outreach strategies included the delivery of newsletters and supplemental packages with materials to promote healthy behavior in the home environment during school summer and winter holiday breaks. In conclusion, the HEALTHY behavior intervention component, when integrated with total school food and physical education environmental changes enhanced by communications and promotional campaigns, is a feasible and acceptable mechanism for delivering age-appropriate social learning for healthy eating and physical activity among an ethnically diverse group of middle school students across the United States.

Do changes in mood and concerns about weight relate to smoking relapse in the postpartum period?

The majority of women who quit smoking during pregnancy will resume smoking during the postpartum period. Little is known, however, about the predictors of postpartum relapses to smoking. Changes in mood and increases in concerns about weight are common during the postpartum period, and these factors may affect women's postpartum smoking behavior. In this paper, we present a model of the relationship among mood, weight concerns and postpartum smoking. Data from previous postpartum relapse prevention trials are reviewed and evidence of a connection between changes in mood and weight concerns to postpartum relapse is presented. Directions for future research on the prevention of smoking relapses during the postpartum period, and the roles of mood and weight concerns in smoking relapse are presented.

Is family-based behavioral weight control appropriate for severe pediatric obesity?

OBJECTIVE: Although the efficacy of family-based behavioral treatment for moderate pediatric obesity has been well established, few studies have focused on the treatment of severe obesity. We sought to evaluate the acceptability and feasibility of a family-based intervention for severely obese children. METHOD: Twenty-four families with children aged 8-12 years who were > or =160% of their ideal body weight participated in a 10-12-session behavioral intervention. Participants were weighed and their heights measured at the start of each treatment session and during a follow-up visit 4-13 (M = 7.8) months posttreatment. Children also completed measures of depressive symptoms and anxiety at pretreatment, posttreatment, and follow-up, and eating attitudes were assessed at pretreatment and follow-up. RESULTS: One third of the families did not complete treatment. However, children who completed the program lost a significant amount of weight and reported significant improvements in depression, anxiety, and eating attitudes that were maintained over time. DISCUSSION: A short-term, family-based behavioral intervention was successful in moderating weight gain for most children and had positive effects on children's mood and eating disorder symptoms. Future randomized, controlled trials of longer interventions are necessary to determine the success of this approach.

The characteristics of women smokers concerned about postcessation weight gain.

Concern about weight gain after quitting smoking is common among women, however, little is known about the characteristics of women concerned about this weight gain. We characterized concerns about smoking and weight, smoking behaviors and eating attitudes among weight-concerned women smokers. Women (N= 219) were participants in a larger trial comparing different approaches to treating postcessation weight gain concerns, and endorsed considerable concern about postcessation weight gain. Women completed assessments of smoking behavior, nicotine dependence and eating attitudes prior to beginning treatment. Although weight-concerned women smokers expected to gain 16.5 lb after quitting, most were willing to tolerate a weight gain of only 5 lb. A substantial number expressed unwillingness to gain any weight at all. However, weight-concerned women did not have elevated nicotine dependency or aberrant eating attitudes. Thus, although weight-concerned women smokers expected to gain large amounts of weight after quitting, they expressed a willingness to tolerate only minimal weight gain. The discrepancy between expected and tolerable weight gain may undermine efforts to quit smoking in this group of women.

Cognitive-behavioral therapy to reduce weight concerns improves smoking cessation outcome in weight-concerned women.

Women smokers concerned about weight gain (N = 219) were randomly assigned to 1 of 3 adjunct treatments accompanying group smoking cessation counseling: (a) behavioral weight control to prevent weight gain (weight control); (b) cognitive-behavioral therapy (CBT) to directly reduce weight concern, in which dieting was discouraged; and (c) standard counseling alone (standard), in which weight gain was not explicitly addressed. Ten sessions were conducted over 7 weeks, and no medication was provided. Continuous abstinence was significantly higher at posttreatment and at 6 and 12 months of follow-up for CBT (56%, 28%, and 21%, respectively), but not for weight control (44%, 18%, and 13%, respectively), relative to standard (31%, 12%, and 9%, respectively). However, weight control, and to a lesser extent CBT, was associated with attenuation of negative mood after quitting. Prequit body mass index, but not change in weight or in weight concerns postquit, predicted cessation outcome at 1 year. In sum, CBT to reduce weight concerns, but not behavioral weight control counseling to prevent weight gain, improves smoking cessation outcome in weight-concerned women.

Psychological correlates of functional hypothalamic amenorrhea.

OBJECTIVE: To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. DESIGN: Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. SETTING: Clinical research center in an academic medical institution. PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.

Sertraline in underweight binge eating/purging-type eating disorders: five case reports.

DISCUSSION: Control trials show that antidepressants are efficacious in eating disorders. Although selective serotonin reuptake inhibitors (SSRIs) are used in clinical practice, there are relatively few controlled or open trials demonstrating that SSRIs are effective. We report five cases of underweight women with binge eating/purging-type eating disorders who gained weight and had reduced core eating disorder behaviors in response to sertraline.

Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

OBJECTIVE: Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. STUDY DESIGN: Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. RESULTS: Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. CONCLUSIONS: In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

How many donuts is a "binge"? Women with BED eat more but do not have more restrictive standards than weight-matched non-BED women.

Theories of disordered eating suggest that binge eating may occur as a response to violations of unrealistically restrictive dietary standards, but there are few direct comparisons of the dietary standards of binge eaters and nonbinge eaters. In this study, we asked obese women with Binge Eating Disorder (BED) and weight- and age-matched women without BED to report the minimum amount of each of eight foods they considered a "binge" and "out of control" to determine whether binge eaters had stricter dietary standards than women without BED. Women with BED did not consider smaller amounts of food a "binge" or "out of control" than did women without BED; however, binge eaters did report that their "typical" and "largest-ever" servings of each of the eight foods were larger than those reported by nonbinge eaters. This suggests that for this group of eating- disordered women, eating behaviors may be a more important intervention target than overly restrictive dietary standards.

Postdoctoral clinical-research training in psychiatry: a model for teaching grant writing and other research survival skills and for increasing clarity of mentoring expectations.

The authors describe a model for teaching grant writing and other research survival skills to postdoctoral clinical-research fellows in psychiatry and for improving research mentoring. Over the past 4 years, the authors have developed a course on writing grant applications for postdoctoral clinical-research fellows, using peer-review processes modeled after a National Institutes of Health study section. At the same time, the authors have clarified expectations of mentors in ways designed to help fellows prepare "K" (Research Career Development) applications and to receive mentored practice in skills being taught in the course. Sixteen of 30 fellows have succeeded in receiving their first extramural support by the end of their two-year fellowship tenure or during the succeeding year. The authors conclude that by teaching grant-writing skills in a supportive peer environment, providing peer review of proposals, and sharpening expectations of mentors, it may be possible to reduce the time between the end of fellowship and the receipt of the first extramural grant.

Prevalence of binge eating disorder, obesity, and depression in a biracial cohort of young adults.

This article examined the prevalence of binge eating disorder (BED), obesity, and depressive symptomatology in a biracial, population-based cohort of men and women participating in a longitudinal study of cardiovascular risk factor development. The Revised Questionnaire on Eating and Weight Patterns was used to establish BED status among the 3,948 (55% women, 48% Black) participants (age 28-40 years). Body mass index (BMI: kg/m2) was used to define overweight (BMI > or = 27.3 in women and > or = 27.8 in men). Depressive symptomatology was assessed with the Center for Epidemiologic Study Depression Scale. Prevalence of BED was 1.5% in the cohort overall, with similar rates among Black women, White women, and White men. Black men had substantially lower BED rates. Depressive symptomatology was markedly higher among individuals with BED. Among overweight participants, BED prevalence (2.9%) was almost double that of the overall cohort. There were no differences in BED rates between over-weight Black and White women. Thus, BED was common in the general population, with comparable rates among Black women, White women, and White men, but low rates among Black men. Obesity was associated with substantially higher prevalence of BED. Treatment studies that target obese men and minority women with BED are indicated.

Differences in salivary habituation to palatable foods in bulimia nervosa patients and controls.

OBJECTIVE: Bulimia nervosa (BN) patients have been shown to experience anomalous responses to food and food cues. We investigated the response to food over time by presenting repeated food cues and measuring changes in physiological (ie, salivation) and subjective responses. METHOD: Subjects were 18 BN women and 18 matched control women. Two palatable food stimuli, regular or frozen yogurt, that varied in macronutrient composition but had similar sensory characteristics, were presented to subjects repeatedly during a laboratory session. After two baseline salivation measures, subjects were presented with eight trials of one of the two yogurts. On Trial 9 a lemon juice dishabituator was presented, with the yogurt stimulus presented again at Trial 10. RESULTS: We found that control subjects had decreased salivation after repeated food presentations. In comparison, BN subjects failed to show a decrease in salivation. The desire to binge increased over trials for the BN subjects, but remained stable for normals. CONCLUSIONS: These data suggest that salivary habituation may be abnormal in BN patients.

Eating behavior following stress in women with and without bulimic symptoms.

OBJECTIVE: This study examined the effects of an interpersonal stressor on subsequent calorie intake in females with (N = 20) and without (N = 20) significant bulimic symptomatology. METHOD: Subjects participated in two laboratory sessions that differed according to experimental condition (stress versus no stress), completed self-report measures of mood and anxiety before and after the experimental task, and were provided with an array of snack foods after each session. RESULTS: Counter to the hypothesis, women with bulimic symptoms did not differentially increase their intake when exposed to stress. However, results for the intake of each macronutrient indicated that both bulimic and control women increased their consumption of carbohydrates following the stressor. Thus, stress was related to increased carbohydrate consumption by all subjects but did not differentially affect the consumption of women with bulimic symptoms. CONCLUSIONS: It may be that women with bulimic symptoms are not differentially vulnerable to eating in response to stress or that current laboratory paradigms are unable to detect differences in eating following a stressor.

Addressing women's concerns about weight gain due to smoking cessation.

Specific concerns about weight gain following smoking cessation inhibit attempts to quit smoking, especially in women. However, adjunct interventions to prevent weight gain after cessation have generally been successful only in attenuating, rather than preventing, weight gain. More aggressive weight control adjuncts may be necessary to prevent cessation-induced weight gain. On the other hand, weight control programs have not been found to improve long-term smoking abstinence and, in fact, may actually impede abstinence, necessitating a search for alternative approaches to addressing weight concerns. Since the typical amount of weight gain is essentially trivial from a health standpoint, particularly when compared with the health benefits of quitting smoking, the most appropriate clinical strategy may be to combat the weight concerns themselves rather than the weight gain. A second alternative approach is to focus all treatment efforts on smoking cessation alone, to avoid placing excessive burdens on participants resulting from attempting simultaneous changes in multiple health behaviors (i.e., smoking and those related to weight). The rationales for these three clinical approaches to addressing concerns about weight gain-more effective weight control, direct reduction in weight concerns by cognitive-behavioral treatment, and smoking cessation only-are presented, followed by descriptions of the adjunct treatments based on these approaches currently being evaluated in a clinical outcome study with women trying to quit smoking.