Mechanisms underlying the development of eating disorders and disordered eating in adolescent females with type 1 diabetes.

OBJECTIVE: People with Type 1 diabetes (T1D) face an increased risk of eating disorders/disordered eating (ED/DE), with adolescents being particularly vulnerable. Empirical knowledge on the mechanisms underlying development of ED/DE in T1D is crucial for evolving prevention strategies. RESEARCH DESIGN AND METHODS: Fourteen semi-structured interviews with adolescent females with T1D and ED/DE between 14 and 18 years were conducted and analyzed using reflexive thematic analysis. RESULTS: Analyses identified four main themes; 'Interconnected afflictions', 'Judgment', 'Feeling Different', and 'Chaos & Control', These themes explore the interconnectedness of T1D and ED/DE, with shame and guilt emerging as common underlying mechanism. The development of a biopsychosocial model was based on the integration of these data with existing models. CONCLUSIONS: The study extends previous developmental pathways of ED/DE in adolescents with T1D. We propose a biopsychosocial model that incorporates various factors: predisposing factors such as parental management of T1D and weight gain during adolescence; precipitating factors including comments on weight, frequency of weighing, perceptions of surveillance; the perpetuating bilateral influence of ED/DE and T1D and finally highlighting the protective mechanisms of disease acceptance encompassing parental handling of diagnosis and the contribution of healthcare professionals (HCP's) role in psychoeducation. The present study highlight the vulnerability of adolescence in the presence of T1D, particularly concerning issues related to eating, weight, and body. It offers clinically relevant insights, with the aim to improve communication and management strategies for this very specific group.

Elevated lipid class concentrations in females with anorexia nervosa before and after intensive weight restoration treatment-A lipidomics study.

OBJECTIVE: To study the plasma lipidome of patients with anorexia nervosa (AN) before and after weight restoration treatment and report associations with AN subtypes and oral contraceptive pill (OCP) usage. METHODS: Quantitative shotgun lipidomics analysis was used to study plasma lipids of 50 female patients with AN before and after weight restoration treatment and 50 healthy female controls (HC). The AN group was assessed with blood samples and questionnaires before and after weight restoration. RESULTS: In total we quantified 260 lipid species representing 26 lipid classes of which 13 lipid class concentrations were elevated in patients with AN at admission compared with HC. Lipid classes remained elevated after weight restoration treatment of 84 days (median; interquartile range 28), and only the concentration of the ceramide lipid class increased between pre- and post-treatment (p = .03), whereas lysophosphatidylcholine (LPC, p = .02), ether-linked Phosphatidylcholine (LPCO, p = .02), and lysophosphatidylethanolamine (LPE, p = .009) decreased. CONCLUSION: In AN, 13 out of 26 lipid class concentrations were elevated at admission and remained elevated post-treatment. Ceramides increased further between pre- and post-weight restoration treatment, which could be related to the rapid weight gain during re-nutrition. Further research is needed to elucidate the effects of weight restoration treatment on short- and long-term lipid profiles in individuals with AN. PUBLIC SIGNIFICANCE STATEMENT: Lipidomics research can increase the understanding of AN, a complex and potentially life-threatening eating disorder. By analyzing lipids, or fats, in the body, we can identify biological markers that may inform diagnosis and develop more effective treatments. This research can also shed light on the underlying mechanisms of the disorder, leading to a better understanding of the processes involved in eating behavior.

Cognitive performance in hospitalized patients with severe or extreme anorexia nervosa.

PURPOSE: Severe malnourishment may reduce cognitive performance in anorexia nervosa (AN). We studied cognitive functioning during intensive nutritional and medical stabilization in patients with severe or extreme AN and investigated associations between weight gain and cognitive improvement. METHODS: A few days after admission to a specialized hospital unit, 33 patients with severe or extreme AN, aged 16-42 years, completed assessments of memory, cognitive flexibility, processing speed, and attention. Mean hospitalization was 6 weeks. Patients completed the same assessments at discharge (n = 22) following somatic stabilization and follow-up up to 6 months after discharge (n = 18). RESULTS: The patients displayed normal cognitive performance at admission compared to normative data. During nutritional stabilization, body weight increased (mean: 11.3%; range 2.6-22.2%) and memory, attention, and processing speed improved (p values: ≤ 0.0002). No relationship between weight gain and cognitive improvement was observed at discharge or follow-up. CONCLUSIONS: Cognitive performance at hospital admission was normal in patients with severe or extreme AN and improved during treatment although without association to weight gain. Based on these results, which are in line with previous studies, patients with severe or extreme AN need not be excluded from cognitively demanding tasks, possibly including psychotherapy. As patients may have other symptoms that interfere with psychotherapy, future research could investigate cognitive functioning in everyday life in patients with severe AN. TRIAL REGISTRATION NUMBER: The study is registered at clinicaltrials.gov (NCT02502617). LEVEL OF EVIDENCE: Level III, cohort study.

Patients' perspectives on screening for disordered eating among adolescents with type 1 diabetes.

PURPOSE: People with type 1 diabetes have an increased risk of disordered eating (DE) and eating disorders (ED). Screening is recommended however little is known about patients' perspectives on screening questionnaires. This paper reports qualitative analyses of patients' perspectives on the questionnaire Diabetes Eating Problem Survey Revised (DEPS-R), including acceptability, attitudes, and cognitive understanding. RESEARCH DESIGN AND METHODS: 15 adolescents with type 1 diabetes between 11 and 18 years, were interviewed. A semi-structured format and a qualitative Interpretive Descriptive (ID) methodology was chosen. RESULTS: The analyses identified four themes: (1) The Questionnaire, (2) Reframing Diabetes Visits, (3) This is (not) for me, and (4) Out in the Open. The DEPS-R was completed with-in 5-10 min. with no technical difficulties. The questionnaire altered the diabetes visit for some, creating a new dialog, and time for self-reflection. Adolescents appreciated the direct approach in the questionnaire, and showed willingness to complete the questionnaire, when presented to them by a health care professional (HCP). One item in the DEPS-R proved difficult to understand for some participants. CONCLUSION: The study highlights DEPS-R as a clinically relevant screening questionnaire. Completing DEPS-R prior to a consultation opens the door to a consultation that invites the adolescent to address matters of eating behavior. Our findings suggest that systematic screening of DE/ED using the DEPS-R is both accepted and welcomed by adolescents with type 1 diabetes. Future research should focus on a potential update of selected items in DEPS-R. LEVEL OF EVIDENCE: V - qualitative study.

Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study.

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls.

Eating disorders and subsequent risk of substance use disorders involving illicit drugs: a Danish nationwide register-based cohort study.

PURPOSE: No study has investigated the ongoing risk of substance use disorders involving illicit drugs (ISUD) after first eating disorder (ED) and whether the pattern of risk differs according to types of ED and ISUD. Therefore, we aimed to longitudinally assess the risk of a subsequent diagnosis of any ISUD (pooled category) and specific ISUD after a first-time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED). METHODS: A retrospective cohort study using data from Danish nationwide registers identified 20,759 ED patients and 83,038 matched controls (1:4 ratio). Risk of any ISUD diagnosis after first ED diagnosis was estimated by generating hazard ratios (HR). Logistic regression was applied to assess associations between each ED and specific ISUD. RESULTS: Patients with AN, BN, and USED (without a prior ISUD diagnosis) exhibited an increased relative risk of a subsequent diagnosis of any ISUD compared with respective controls, and the elevated risk persisted over 10 years (AN, adjusted HRs ranging from 1.60 [99% CI 1.15-2.24] to 5.16 [3.14-8.47]; BN, 2.35 [1.46-3.79] to 14.24 [6.88-29.47]; USED, 2.86 [1.35-3.79] to 8.56 [3.31-29.47]). The highest estimates were observed during the first year of follow-up. Each ED type was associated with an increased likelihood of all types of ISUD. AN and USED were most strongly associated with sedatives/hypnotics, BN with other illegal substances (e.g., ecstasy and hallucinogens). CONCLUSIONS: ED patients have a considerable risk for subsequent ISUD. Prevention efforts and treatment targeting ISUD are likely required to improve ED treatment prognosis.

Validating the Danish version of the Eating Disorder Quality of Life Scale (EDQLS) in anorexia nervosa.

PURPOSE: The aim of this study was to explore the factor structure of the Danish translation of the eating disorder quality of life scale and evaluate the internal reliability and convergent validity of the scale in a Danish cohort of women with AN. METHODS: The total sample comprised 211 patients diagnosed with anorexia nervosa age 13-40 years. Patients completed questionnaires assessing eating disorder psychopathology, physical and social functioning, and well-being. RESULTS: Factor analyses were not able to support the current division of the scale into 12 factors. We found excellent internal consistency of the eating disorder quality-of-life scale total score. We found relevant associations between quality of life and pre-determined variables. CONCLUSION: This study supports the use of the total score of the eating disorder quality of life scale in assessing quality of life in patients with anorexia nervosa. However, future studies should explore the factor structure of the scale further. LEVEL OF EVIDENCE: III: Evidence obtained from cohort or case-control analytic studies.

Comorbid mental disorders during long-term course in a nationwide cohort of patients with anorexia nervosa.

OBJECTIVE: Comorbid mental disorders in anorexia nervosa during long-term course require detailed studies. METHOD: This matched cohort study was based on nationwide Danish register data of all patients born 1961-2008 with a first-time ICD-10 diagnosis of anorexia nervosa (AN) between 1994 and 2018 at age 8-32 and matched controls taken from all individuals without an eating disorder (ED). For nine categories of non-eating mental disorders, time from date of first AN-diagnosis (inclusion date) to time of first diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9,985 patients with AN (93.5% females) and 49,351 matched controls were followed for a median (IQR) of 9.0 (4.4-15.7) years. For patients, there was about 25% and 55% risk of receiving any non-ED disorder during the first 2 years and two decades after inclusion, respectively. A hazard ratio (HR) of seven for any non-ED was found for the first 12 months after inclusion, a ratio that reduced to two at five or more years after inclusion. During the first years, large HRs ranging in 6-9 were found for affective, autism spectrum, personality, and obsessive-compulsive disorders with the latter displaying the highest continuous increased risk. The HR at 12 months after inclusion was highest for any non-ED disorder and affective disorders in patients aged 8-13 at diagnosis. DISCUSSION: Comorbid mental disorders in AN are most frequently diagnosed in the first years after diagnosis of AN and on longer terms imply a double immediate risk.

Cognitive improvement following weight gain in patients with anorexia nervosa: A systematic review.

OBJECTIVE: Anorexia nervosa (AN) has been associated with cognitive impairment. While re-nutrition is one of the main treatment targets, the effect on cognitive impairments is unclear. The aim of this review was to examine whether cognitive functions improve after weight gain in patients with AN. METHOD: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines (PROSPERO CRD42019081993). Literature searches were conducted May 20th , 2019 in PubMed, EMBASE, PsychINFO and Cochrane Library. Pairs of reviewers screened reports independently based on titles/abstracts (N = 6539) and full texts (N = 378). Furthermore, they assessed the quality of reports, including whether practice effects were accounted for. RESULTS: Twenty-four longitudinal reports were included featuring 757 patients and 419 healthy controls. Six studies examined children and adolescents. Four out of four studies found processing speed to improve above and beyond what could be assigned to practice effects and three out of four studies found that cognitive flexibility was unaffected after weight gain in children and adolescents. Results from studies of adults were inconclusive. DISCUSSION: The literature on cognitive change in patients with AN following weight gain is sparse. Preliminary conclusions can be made only for children and adolescents, where weight gain appeared to be associated with improved processing speed.

Time trends in treatment modes of anorexia nervosa in a nationwide cohort with free and equal access to treatment.

BACKGROUND: Treating patients with anorexia nervosa (AN) remains a major challenge. The choice between an inpatient or an outpatient care setting is an essential issue for the patients and for their relatives with major health economic implications. However, health services-related studies are lacking. The present study was a descriptive exploration of time-trends in treatment modes of patients with free and equal access to health services. METHODS: The study was based on a nationwide cohort of patients diagnosed for the first time with AN, each followed for 5 years in the registers covering the years 1994-2018. The per patient number of hospital admissions, cumulated number of days of hospitalization and number of outpatient visits during the first 5 years after initial diagnosis were considered. RESULTS: The cohort of patients with AN with at least 5 years of follow-up amounted to N = 7,505. A clear trend was observed in the per patient five-year cumulated number of inpatient days, decreasing by 6% per year after adjustment for age at diagnosis, parental mental diagnosis, and family income. The five-year number of hospital admissions after initial diagnosis decreased by 2% per year, while no trend was observed for outpatient visits. CONCLUSIONS: The per patient number of hospitalizations and cumulated days of hospitalization during 5 years after diagnosis were reduced for patients initially diagnosed with AN while there was no change in the number of outpatient visits. The factors contributing to these changes of treatment modes over time are in need of further study.

Case report: cognitive performance in an extreme case of anorexia nervosa with a body mass index of 7.7.

BACKGROUND: Studies show that adult patients with anorexia nervosa display cognitive impairments. These impairments may be caused by illness-related circumstances such as low weight. However, the question is whether there is a cognitive adaptation to enduring undernutrition in anorexia nervosa. To our knowledge, cognitive performance has not been assessed previously in a patient with anorexia nervosa with a body mass index as low as 7.7 kg/m2. CASE PRESENTATION: We present the cognitive profile of a 35-year-old woman with severe and enduring anorexia nervosa who was diagnosed at the age of 10 years. She was assessed with a broad neuropsychological test battery three times during a year. Her body mass index was 8.4, 9.3, and 7.7 kg/m2, respectively. Her general memory performance was above the normal range and she performed well on verbal and design fluency tasks. Her working memory and processing speed were within the normal range. However, her results on cognitive flexibility tasks (set-shifting) were below the normal range. CONCLUSIONS: The case study suggests that it is possible to perform normally cognitively despite extreme and chronic malnutrition though set-shifting ability may be affected. This opens for discussion whether patients with anorexia nervosa can maintain neuropsychological performance in spite of extreme underweight and starvation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02502617. Registered 20 July 2015.

Hunger and satiety perception in patients with severe anorexia nervosa.

OBJECTIVES: Appetite is a subjective essential sense. In patients with severe anorexia nervosa (AN), controversy remains whether this sensation is altered. The objectives were to clarify, in patients with severe AN: (1) Whether the appetite changes during partial weight restoration, (2) Whether potential changes in appetite are related to (i) diagnostic subtype of AN, (ii) psychopharmacological treatment, (iii) disease duration, (iv) duration of hospitalization, and (v) baseline body mass index (BMI). METHODS: The study consisted of 39 patients, with a mean age of 23.7 ± 8 and an admission mean BMI of 13.1 ± 2.0 kg/m2. The patients were consecutively admitted to a specialized somatic nutrition unit between 2015 and 2016. They were asked to rate their hunger and satiety on a numeric visual analog scale (VAS), before and after a lunch meal at admission and at discharge in the same standardized environment. The patients could participate more than once if readmitted, resulting in a total of 119 observed meals. Data were analyzed in a regression model for repeated measures. RESULTS: At admission, changes in hunger and satiety perception were weak. After weight gain of 10.4% ± 8.5% within a median of 26 (IQR: 25) days, there was a slight increase in hunger perception, p = 0.049. However, there was no detectable change in satiety perception. There was no noticeable correlation between appetite change and psychopharmacological treatment, diagnostic subtype, BMI, duration of hospitalization, and disease duration. CONCLUSION: Hospitalized patients with severe AN exhibit strikingly weak changes in hunger and satiety perception during standardized and supervised meals. LEVEL OF EVIDENCE: Level IV, evidence obtained from multiple time series analysis.

Venous thromboembolism in anorexia nervosa: four cases from a specialized unit. Indication for thromboprophylaxis?

BACKGROUND: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of mortality and morbidity. VTE may occur asymptomatic or subclinical. Fluid retention during intensive re-nutrition or rapid weight changes are well-known phenomena in anorexia nervosa (AN) and may represent a significant risk factor for VTE. OBJECTIVE: The incidence of VTE in patients with AN is unknown, and the conditions may be overlooked in a complex clinical picture. METHOD: This study report four cases of VTE in women with severe AN (age range 19-41 years, BMI range 10.6-13.1) admitted to a specialized unit for medical stabilization. RESULTS: DVT or PE was diagnosed in all four patients. The patients were admitted for intensive re-nutrition according to conventional conservative guidelines with slow increase in energy supply (start low and advance slow). Due to suspected VTE, thromboprophylaxis was given during hospitalization, three of whom were undergoing re-nutrition. CONCLUSION: The four presented cases suggest that VTE during re-nutrition in AN may be an overlooked risk which may not be sufficiently addressed in the literature. General recommendations should not be issued on the basis of case reports; however, we want to raise awareness and call for studies to identify the VTE risk and appropriate thromboprophylaxis in AN patients.

The BODY-Q Stretch Marks Scale: A Development and Validation Study.

BACKGROUND: Stretch marks are common permanent dermal lesions that can cause psychosocial distress. A number of treatment modalities are available, with the majority targeted towards collagen production. OBJECTIVES: To develop and field test a new BODY-Q scale to measure appearance of stretch marks in order to provide a means to incorporate the patient perspective into future treatment studies. METHODS: We previously described the development of the BODY-Q conceptual framework, which involved a literature review, 63 patient interviews, 22 cognitive interviews and input from 9 experts, and the international field-test study that involved 403 weight loss and 331 body contouring patients. To develop the Stretch Marks scale, we reexamined appearance codes from the original interviews. The scale was field tested in an international study. Rasch measurement theory (RMT) analysis was used to refine the scale and examine measurement properties. RESULTS: The Stretch Marks scale was completed by 630 participants, who provided 774 assessments. After dropping 3 items, the data fit the Rasch model (P = 0.56). Items (eg, length, width, amount, location, up close) mapped out a well-targeted clinical hierarchy. All items had ordered thresholds and good item fit. There was no evidence of differential item functioning (bias) by gender, age group or language (English vs Danish). The scale evidenced high reliability (ie, person separation index = 0.94, Cronbach's alpha = 0.97). For construct validity, the mean score correlated with the total number of body areas with stretch marks, higher BMI before bariatric surgery, and other BODY-Q scales. CONCLUSIONS: This scale could be used to measure the impact of innovative treatments for stretch marks.

Body composition and menstrual status in adults with a history of anorexia nervosa-at what fat percentage is the menstrual cycle restored?

OBJECTIVE: To study the association between body composition measures and menstrual status in a large sample of adult patients with a history of anorexia nervosa and to calculate the predicted probability of resumption of menstrual function. Furthermore, to establish whether fat percentage is superior to body mass index in predicting the resumption of menses. METHOD: One hundred and thirteen adult women with a history of anorexia nervosa underwent a dual energy X-ray absorptiometry (DXA) scan and completed questionnaires regarding medication prescription and menstrual function. RESULTS: Fifty percent of patients were expected to resume their menstrual function at a body mass index of 19 kg m-2 or a fat percentage of 23%. Twenty-five percent of patients were expected to resume their menstrual function at body mass index 14 kg m-2 or fat percentage 11%. Fat percentage and body mass index were equally capable of predicting the resumption of menses. DISCUSSION: Fat percentage and body mass index were positive predictors of the resumption of menses, however, body composition measured by dual energy X-ray absorptiometry was not superior to body mass index in predicting menstrual recovery, which is of great clinical relevance as body mass index is easier and cheaper to obtain. Body composition measures only account for one of numerous factors involved in the resumption of menses. Regression models based on our data had a R2 value of 0.14, indicating that only 14% of the variation in menstrual recovery could be explained by the variables included. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:370-377).

Identification of eating disorder symptoms in Danish adolescents with the SCOFF questionnaire.

BACKGROUND: Eating disorders often develop in adolescence and, therefore, instruments are needed that are useful to detect risk behaviour in young people. The SCOFF is a 5-item screening instrument, named SCOFF as an acronym of keywords from the questions. It has been used widely in adult samples, but studies that evaluate the scale in adolescents are missing. AIMS: The aim of this study was to test the psychometric properties of the SCOFF in adolescents aged 11-20 years and for the first time validate the questionnaire in Danish. METHODS: A total of 184 adolescents completed the Danish version of the SCOFF and sub-scales from the Eating Disorder Inventory (EDI-3). The sample consisted of 87 patients (mean age = 16) from a specialized eating disorder department in the Region of Southern Denmark and 97 healthy adolescents (mean age = 17) from Danish primary and high schools. RESULTS: It was found that the reliability of the SCOFF was acceptable, and that cut-off 2 is useful to detect those with potential eating disorder pathology. Item 3 (weight loss) correlated poorly with EDI-3 sub-scales and might be reformulated by addressing the intentionality behind weight loss (due to unhappiness with body) rather than a specific amount of weight loss (1 stone), because this could have somatic reasons. CONCLUSIONS: The SCOFF is a very easily applicable questionnaire, which may fulfil the necessary psychometric properties for detection of ED symptoms in Danish adolescents. Before general screening can be recommended, conditions regarding benefits and potential adverse effects still remain to be addressed.

Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese patients (10 males, 15 females). Patients were examined with DXA of the hip and spine, HR-pQCT of radius and tibia, and blood sampling before and 6 and 12 months after RYGB. Patients lost in average 33.5 ± 12.1 kg (25.8 ± 8.5 %) in 12 months. In tibia, we found significant loss of total, cortical and trabecular volumetric BMD after 12 months (all p < 0.001). Microarchitectural changes involved lower trabecular number, increased trabecular separation, and network inhomogeneity along with thinning of the cortex. Estimated bone failure load was decreased after 12 months (p = 0.005). We found only minor changes in radius. Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which resulted in a loss of estimated bone strength in tibia. Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.

Effect of dronabinol therapy on physical activity in anorexia nervosa: a randomised, controlled trial.

PURPOSE: The level of physical activity is inappropriately high in up to 80% of the patients suffering of anorexia nervosa (AN), as a result of conscious efforts to lose weight, affect regulation and biological adaptive changes to starvation induced by hypothermia and neuroendocrine mechanisms. The purposes of this paper were to (1) assess the effect of dronabinol-a synthetic cannabinoid agonist-on physical activity in patients with chronic and stable AN, and to (2) unravel the role of leptin and cortisol in this process. METHODS: This prospective, randomised, double-blind, crossover study was conducted at a specialised care centre for eating disorders. Twenty-four adult women with AN of at least 5-year duration received either the dronabinol-placebo or placebo-dronabinol sequence. Physical activity was monitored during the fourth week of each intervention. Body weight, leptin and urinary free cortisol excretion were measured repeatedly during the trial. Changes in behavioural dimensions related to AN were assessed by Eating Disorder Inventory-2. RESULTS: The total duration of physical activity did not change, while its average intensity increased by 20% (P = 0.01) during dronabinol therapy, resulting in an increased energy expenditure with 68.2 kcal/day (P = 0.01) above placebo. CONCLUSIONS: This randomised, double-blind study revealed that cannabinoid agonist treatment was associated with a modest increase in physical activity in adult women with severe and longstanding AN. Additionally, we detected a strong relationship between the circulating levels of leptin and physical activity in these chronically undernourished patients.

Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography.

Obesity is associated with high bone mineral density (BMD), but whether obesity-related higher bone mass increases bone strength and thereby protect against fractures is uncertain. We estimated effects of obesity on bone microarchitecture and estimated strength in 36 patients (12 males and 24 females, age 25-56 years and BMI 33.2-57.6 kg/m(2)) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m(2)) in regard to gender, menopausal status, age (±6 years) and height (±6 cm) using high resolution peripheral quantitative computed tomography and dual energy X-ray absorptiometry. In radius, total bone area and trabecular area were significantly higher in obese patients (both p < 0.04). In tibia, cortical area was larger in obese patients (p < 0.001) compared with controls. Total BMD was higher in tibia (p = 0.03) but not in radius. Trabecular integrity was strengthened in obese patients compared with controls in radius and tibia with higher trabecular number (p = 0.002 and p < 0.001) and lower trabecular spacing (p = 0.01 and p < 0.001). Finite element analysis estimated failure load (FL) was higher in tibia (p < 0.001), but not in radius in obese patients. FL was significantly lower per kg body weight in radius and tibia in obese patients compared with controls (p = 0.007 and p < 0.001). Furthermore, the ratios of FLs between groups were comparable in both sites. These findings suggest that mechanical loading is not the primary mediator of the effects of obesity on estimated FL, and suggest that bone strength adaptations in morbid obesity may be inadequate with respect to the increased mechanical demands.

Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial.

OBJECTIVE: The evidence for pharmacological treatment of severe, longstanding anorexia nervosa (AN) is sparse and the few controlled pharmacologic studies have focused on a narrow range of drugs. The aim of the present study was to investigate the effects of treatment with a synthetic cannabinoid agonist on body weight and eating disorder-related psychopathological personality traits in women with severe, enduring AN. METHOD: This add-on, prospective, randomized, double blind, controlled crossover study was conducted between 2008 and 2011 at a specialized care center for eating disorders. Twenty-five women over 18 years with AN of at least 5 years duration were randomized to treatment with either dronabinol-placebo or placebo-dronabinol. In addition to the standardized baseline therapeutic regime, the participants received dronabinol, 2.5 mg twice daily for 4 weeks and matching placebo for 4 weeks, separated by a 4-week wash-out period. Primary outcome was the mean change in body weight. Secondary outcome was score changes on the Eating Disorder Inventory-2 (EDI-2). Data were analyzed for the 24 patients who completed the trial. RESULTS: During dronabinol treatment, participants gained 0.73 kg (t = 2.86, df = 22, p < 0.01) above placebo without significant psychotropic adverse events. Dronabinol significantly predicted weight gain in a multiple linear regression including EDI-2 body dissatisfaction score and leptin. EDI-2 subscale scores showed no significant changes over time. DISCUSSION: Dronabinol therapy was well tolerated. During four weeks of exposure it induced a small but significant weight gain in the absence of severe adverse events.