The Relationship between Patient Self-Reported, Pre-Morbid Physical Activity and Clinical Outcomes of Inpatient Treatment in Youth with Anorexia Nervosa: A Pilot Study.

Links between premorbid physical activity (PA) and disease onset/course in patients with anorexia nervosa (AN) remain unclear. The aim was to assess self-reported PA as a predictor of change in percent median BMI (%mBMI) and length of hospital stay (LOS). Five PA domains were assessed via semi-structured interview in adolescents with AN at hospitalization: premorbid PA in school grades 1-6 (PA1-6); PA before AN onset (PA-pre) and after AN onset (PA-post); new, pathological motivation for PA (PA-new); and high intensity PA (PA-high). Eating disorder psychopathology was measured via the Eating Disorder Examination Questionnaire (EDE-Q), and current PA (steps/day) with accelerometry. PA1-6 was also assessed in healthy controls (HCs). Using stepwise backward regression models, predictors of %mBMI change and LOS were examined. Compared with 22 HCs (age = 14.7 ± 1.3 years, %mBMI = 102.4 ± 12.1), 25 patients with AN (age = 15.1 ± 1.7 years, %mBMI = 74.8 ± 6.0) reported significantly higher PA1-6 (median, AN = 115 [interquartile range IQR = 75;200] min vs. HC = 68 [IQR = 29;105] min; p = 0.017). PA-post was 244 ± 323% higher than PA-pre. PA1-6 was directly associated with PA-pre (p = 0.001) but not with PA-post (p = 0.179) or change in PA-pre to PA-post (p = 0.735). Lower %mBMI gain was predicted by lower baseline %mBMI (p = 0.001) and more PA-high (p = 0.004; r2 = 0.604). Longer LOS was predicted by higher PA-pre (p = 0.003, r2 = 0.368). Self-reported PA may identify a subgroup of youth with AN at risk of less weight gain and prolonged LOS during inpatient treatment for AN.

The Diagnosis and Treatment of Anorexia Nervosa in Childhood and Adolescence.

BACKGROUND: Anorexia nervosa (AN) is a serious disease with a lifetime prevalence of up to 3.6% in women and 0.3% in men. Abnormally low weight and the associated starvation partly account for its somatic and mental manifestations. METHODS: This review is based on publications retrieved by a selective search concerning AN in childhood and adolescence. RESULTS: The peak age of onset of AN is 15.5 years. The frequency of inpatient treatment for AN rose by 40% during the COVID pandemic, indicating the importance of environmental factors; the heritability of AN is estimated at 0.5. The ICD-11 sets the threshold for AN-associated underweight at the fifth percentile for age of the body mass index, as long as the remaining diagnostic criteria are met. The main goal of the multiprofessional treatment of AN is the return to normal body weight, which is a central prerequisite for regaining somatic and mental health. The mean duration of AN is 3.4 years, and approximately twothirds of patients recover from the disease over the long term. CONCLUSION: Marked weight loss in childhood and adolescence can trigger AN in the presence of a predisposition to this disease. Patients and their families should receive psychoeducation regarding the symptoms of starvation and their overlap with those of AN. Important objectives are to shorten the duration of the illness, minimize mortality and the risk of chronic illness, and to identify pharmacological approaches to treatment.

Comparing family-based treatment with inpatient treatment in youth with anorexia nervosa eligible for hospitalization: A 12-month feasibility study.

OBJECTIVE: Family-based treatment (FBT) for youth with anorexia nervosa (AN), has not been compared to inpatient, multimodal treatment (IMT). METHOD: Prospective, non-randomized pilot feasibility study of adolescents with AN receiving FBT (n = 31), and as a reference point for exploratory outcome comparisons IMT (n = 31), matched for baseline age and percent median BMI (%mBMI). Feasibility of FBT in youth fulfilling criteria for IMT was assessed via study recruitment and retention rates; acceptability via drop-out and caregiver strain; safety via adverse events; preliminary treatment effectiveness between groups was assessed via a change in %mBMI, AN psychopathology (Eating Disorder Examination-Questionnaire, EDE-Q), and hospital days, over 12 months with intent-to-treat, mixed models repeated measures analyses covering post-intervention usual care until 12 months. RESULTS: Taking into account that 8 FBT patients (25.8%) crossed over to IMT due to lack of weight gain or psychiatric concerns, FBT and IMT were similarly feasible, acceptable, and safe, apart from more physical antagonism toward others in FBT (p = .010). FBT lasted longer (median [interquartile range, IQR]; 33.6 [17.4, 49.9] vs. 17.3 [14.4, 24] weeks, p < .001), but required fewer hospital days than IMT (median, [IQR], FBT = 1 [0, 16] vs. IMT = 123 [101, 180], p < .001). Baseline comorbidity-adjusted changes over 12 months did not differ between groups in %mBMI (FBT = 12.6 ± 11.9 vs. IMT = 13.7 ± 9.1; p = .702) and EDE-Q global score (median, [IQR]; FBT = -1.2 [-2.3, 0.2] vs. IMT = -1.3 [-2.8, -0.4]; p = .733). DISCUSSION: Implementing FBT in this pilot study was feasible, acceptable, and safe for youth eligible for IMT according to German S3 guidelines. Non-inferiority of FBT versus IMT requires confirmation in a sufficiently large multicenter RCT. PUBLIC SIGNIFICANCE: This pilot study with 62 adolescent patients with anorexia nervosa demonstrated that for 2/3rd of patients eligible for a long hospitalization in the German health care system, outpatient, Family-based treatment (FBT) was a safe and feasible treatment alternative. Over 12 months, FBT lead to similar weight gain and reduction in eating disorder cognitions as inpatient treatment with fewer hospital days. This pilot study needs to be followed up by a larger, multicenter trial.

Prediction of activity-related energy expenditure under free-living conditions using accelerometer-derived physical activity.

The purpose of the study was to develop prediction models to estimate physical activity (PA)-related energy expenditure (AEE) based on accelerometry and additional variables in free-living adults. In 50 volunteers (20-69 years) PA was determined over 2 weeks using the hip-worn Actigraph GT3X + as vector magnitude (VM) counts/minute. AEE was calculated based on total daily EE (measured by doubly-labeled water), resting EE (indirect calorimetry), and diet-induced thermogenesis. Anthropometry, body composition, blood pressure, heart rate, fitness, sociodemographic and lifestyle factors, PA habits and food intake were assessed. Prediction models were developed by context-grouping of 75 variables, and within-group stepwise selection (stage I). All significant variables were jointly offered for second stepwise regression (stage II). Explained AEE variance was estimated based on variables remaining significant. Alternative scenarios with different availability of groups from stage I were simulated. When all 11 significant variables (selected in stage I) were jointly offered for stage II stepwise selection, the final model explained 70.7% of AEE variance and included VM-counts (33.8%), fat-free mass (26.7%), time in moderate PA + walking (6.4%) and carbohydrate intake (3.9%). Alternative scenarios explained 53.8-72.4% of AEE. In conclusion, accelerometer counts and fat-free mass explained most of variance in AEE. Prediction was further improved by PA information from questionnaires. These results may be used for AEE prediction in studies using accelerometry.

Outcomes of a Standardized, High-Caloric, Inpatient Re-Alimentation Treatment Protocol in 120 Severely Malnourished Adolescents with Anorexia Nervosa.

Evidence accumulates that, with close medical monitoring and phosphate supplementation, higher-caloric re-alimentation protocols beginning at 2000 kcal/day (HCR) are not associated with an increased incidence of electrolyte abnormalities in patients with anorexia nervosa (AN) but rather result in faster weight gain. These studies are still scant and have largely been performed in adults or moderately malnourished adolescents. Methods: A retrospective chart review of patients with AN aged 12−20 years and with a body mass index (BMI) < 15 kg/m2 alimented according to a standardized treatment protocol in a German clinic specialized in AN was conducted. All patients received 2000 kcal/day from day one. The effect of HCR was examined with respect to laboratory changes and weight development over 4 weeks. Results: In 120 youth (119 (99.2%) females and 1 (0.8%) male, the mean BMI was 13.1 ± 1.1 (range = 10.2−15.0), %mBMI was 62.1 ± 6.0% and weight gain was 0.76 ± 0.22 kg per week, with the highest rate of weight gain during week 1 (1.25 ± 1.28 kg/week). Over 4 weeks, the total weight gain was 3.00 ± 1.92 kg. Nine patients (7.5%) developed mild hypophosphatemia, and none developed refeeding syndrome. Conclusions: Starting re-alimentation with 2000 kcal/d under close medical surveillance, severely malnourished youth with AN met the recommended weight gain targets between 0.5 and 1 kg/week according to current treatment guidelines, without anyone developing refeeding syndrome.

Comparing randomized controlled trials of outpatient family-based or inpatient multimodal treatment followed by outpatient care in youth with anorexia nervosa: Differences in populations, metrics, and outcomes.

OBJECTIVE: Various approaches exist to treat youth with anorexia nervosa (AN). Family-based treatment (FBT) has never been compared to long inpatient, multimodal treatment (IMT) in a randomized controlled trial (RCT). The aim of this study was to compare data on body weight trajectories, change in eating disorder psychopathology, hospital days and treatment costs in RCTs delivering FBT or IMT. METHOD: Review of RCTs published between 2010 and 2020 in youth with AN, delivering FBT or IMT. RESULTS: Four RCTs delivering FBT (United States, n = 2; Australia, n = 2), one RCT delivering Family Therapy for AN (United Kingdom) and two RCTs delivering IMT (France, n = 1; Germany, n = 1) were identified from previous meta-analyses. The comparison of studies was limited by (1) significant differences in patient baseline characteristics including pretreated versus non-pretreated patients, (2) use of different psychometric and weight measures and (3) different initial velocity of weight recovery. Minimal baseline and outcome reporting standards for body weight metrics and nature/dose of interventions allowing international comparison are needed and suggestions to developing these standards are presented. DISCUSSION: An RCT should investigate, whether FBT is a viable alternative to IMT, leading to comparable weight and psychopathology improvement with less inpatient time and costs.

The Impact of Inpatient Multimodal Treatment or Family-Based Treatment on Six-Month Weight Outcomes in Youth with Anorexia Nervosa: A Naturalistic, Cross-Continental Comparison.

In the USA, family-based treatment (FBT) with inpatient medical stabilization as needed is the leading evidence-based treatment for youth with anorexia nervosa (AN). In continental Europe, typically inpatient multimodal treatment targeting weight recovery followed by outpatient care (IMT) is standard care, if prior outpatient treatment was not sufficient. Our aim was to compare weekly weight gain and hospital days over six months for adolescents receiving FBT (USA) versus IMT (Germany) using naturalistic treatment data. To yield similar subgroups of youth aged 12−18 years, inclusion criteria were a percent median BMI (%mBMI) between 70−85 and the restrictive AN subtype. Weight gain and hospital days were compared, adjusted further in a multiple linear regression analysis (MLRA) for baseline group differences. Samples differed on baseline %mBMI (FBT [n = 71], 90.5 ± 12.8; IMT [n = 29], 78.3 ± 9.1, p < 0.05). In subgroups with comparable baseline %mBMI, the weekly weight gain over 6 months was similar (FBT [n = 21]: 0.35 ± 0.18 kg/week; IMT [n = 20]: 0.30 ± 0.18, p = 0.390, p = 0.166 after MLRA), but achieved fewer hospital days in FBT (FBT [n = 7]: 4 ± 6 days, IMT [n = 20]: 121 ± 42 days, p < 0.0001 before and after MLRA). FBT may be effective for a subgroup of adolescents with AN currently receiving IMT, but head-to-head studies in the same healthcare system are needed.

Early childhood neurodevelopmental outcome after open prenatal spina bifida aperta repair.

AIM: To investigate neurodevelopmental outcome of children with open prenatal spina bifida aperta (SBA) repair. METHOD: Prenatal SBA repair was performed in 130 fetuses at the Zurich Center between 2010 and 2019. Seventy-seven children underwent 1 year assessment with the Griffiths Mental Developmental Scales (Griffiths) and 65 with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years. Anatomical and functional level and ambulation status were assessed. Descriptive statistics and multiple linear regression analyses for risk factors were performed. RESULTS: The Bayley-III cognition composite score in children with prenatal SBA repair was within normal limits but lower compared to population norms (mean=95.15, SD=14.683 vs norm=100, SD=15, p=0.01). Fine motor development (mean=9.58, SD=2.744, p=0.227) was typical while gross motor development was lower than the norm (mean=3.02, SD=2.758 vs norm=10, SD=3, p<0.001). Griffiths developmental quotient subscales correlated significantly with corresponding Bayley-III scores (all p<0.001, r=0.519-0.594). At 2 years, 50.8% could walk. INTERPRETATION: Children with non-trial open prenatal SBA repair show favourable cognitive outcome in the low-average range at 1 and 2 years of age. While gross motor function remained delayed, fine motor function was age appropriate. The correlation between Griffiths and Bayley-III allows a prediction about neurodevelopmental outcome at the age of 1 year. What this paper adds Children with non-trial open prenatal spina bifida repair show favourable cognitive outcome. Gross motor function remains impaired, while fine motor function is age appropriate. At 2 years of age, 50.8% of children were walking. Neurodevelopmental testing correlated between 1 (Griffiths Mental Developmental Scales) and 2 (Bayley Scales of Infant and Toddler Development, Third Edition) years.

Practice-Based Evidence and Clinical Guidance to Support Accelerated Re-Nutrition of Patients With Anorexia Nervosa.

Anorexia nervosa (AN) is characterized by underweight, and the primary goal of treatment is weight restoration. Treatment approaches (ie, hospitalization for weight recovery vs for medical stabilization) and settings (ie, medical/pediatric or psychiatric units) for patients with AN vary between and also within countries. Several specialized eating disorder units worldwide have established high-caloric refeeding (HCR) protocols for patients with AN. In observational studies, HCR shortens hospital stays and increases initial weight gain, the latter being associated with a favorable long-term prognosis. However, clinicians may still remain reluctant to accept this approach for fear of medical complications of HCR, including the risk of refeeding syndrome (RS).1 Research is building toward the development of evidence-based recommendations for safe and effective re-nutrition of underweight patients with AN. This focused review was based on clinical experience and describes 3 different protocols for nutritional management devised by experts from 3 different parts of the world (Australia, Germany, and the United States), in medical refeeding of patients with AN who have established HCR in their clinical units. In addition, and in order to understand energy requirements, empirical data on energy turnover of patients with AN from former metabolic studies are presented. To the best of our knowledge, there is no study reporting on HCR in a cohort of severely malnourished adolescents with AN (ie, with a mean body mass index [BMI] of <15 kg/m2). Therefore, to provide information about the treatment of extremely malnourished patients with AN, we included a recently published HCR protocol for adults with a BMI of <13 kg/m2.2.

Medical management of eating disorders: an update.

PURPOSE OF REVIEW: Eating disorders are associated with numerous medical complications. The aim of this study was to review recent progress in improving the medical management of patients with eating disorders. RECENT FINDINGS: With close medical monitoring and electrolyte supplementation, accelerated refeeding protocols improve weight restoration without increasing the risk of refeeding syndrome. Olanzapine improves weight restoration better than placebo, without leading to adverse metabolic effects seen in individuals not in starvation. Alterations of the gut microbiome in anorexia nervosa have been demonstrated, but their clinical relevance remains unclear. SUMMARY: Medical complications of eating disorders may facilitate the first contact with health professionals and treatment initiation. Medical complications of anorexia nervosa generally occur due to starvation, malnutrition and their associated physiological effects, whereas medical complications of bulimia nervosa are generally due to purging behaviors. Most medical complications in patients with binge eating disorder are secondary to obesity. Most medical complications of eating disorders can be effectively treated with nutritional management, weight normalization and the termination of purging behaviors. In summary, eating disorders are associated with many medical complications that have to be carefully assessed and managed as early as possible to improve long-term outcomes.

Psychological and nutritional correlates of objectively assessed physical activity in patients with anorexia nervosa.

BACKGROUND: Physical activity (PA) plays a role in the course of anorexia nervosa (AN). OBJECTIVE: To assess the association between PA, nutritional status and psychological parameters in patients with AN. METHOD: Using a wearable activity monitor, PA was assessed in 60 female AN inpatients, by step count and time spent in 4 metabolic equivalent (MET)-intensity levels: sedentary behaviour, light, moderate and vigorous PA. In addition, BMI, psychological (patient-reported outcome questionnaires) and nutritional parameters (body fat, energy and macronutrient intake) were assessed. RESULTS: The study population spent little time in vigorous PA. BMI on admission and discharge was higher when more time was spent in sedentary behaviour, and lower with more time spent in light PA. Relationships between PA and patient-reported outcomes were weak and limited to an association between vigorous PA and compulsiveness. Low fat mass was associated with more time spent in light PA, while subjects with higher step counts showed less intake of energy, carbohydrates and fat. CONCLUSION: The relationship between inadequate food intake and increased PA in patients with AN requires further investigation.

Outcomes of an Accelerated Inpatient Refeeding Protocol in 103 Extremely Underweight Adults with Anorexia Nervosa at a Specialized Clinic in Prien, Germany.

BACKGROUND: In mildly to moderately malnourished adolescent patients with anorexia nervosa (AN), accelerated refeeding protocols using higher initial calory supply coupled with phosphate supplements were not associated with a higher incidence of refeeding syndrome (RS). It is unclear whether this is also a feasible approach for extremely malnourished, adult AN patients. METHODS: Outcomes of a clinical refeeding protocol involving a targeted initial intake of ≥2000 kcal/day, routine supplementation of phosphate and thiamine as well as close medical monitoring, were evaluated. A retrospective chart review including AN patients with a body mass index (BMI) <13 kg/m² was conducted, to describe changes in weight, BMI, and laboratory parameters (phosphate, creatine kinase, hematocrit, sodium, liver enzymes, and blood count) over four weeks. RESULTS: In 103 female patients (age, mean ± standard deviation (SD) = 23.8 ± 5.3 years), BMI between admission and follow-up increased from 11.5 ± 0.9 to 13.1 ± 1.1 kg/m² and total weight gain within the first four weeks was 4.2 ± 2.0 kg (mean, SD). Laboratory parameter monitoring indicated no case of RS, but continuous normalization of blood parameters. CONCLUSIONS: Combined with close medical monitoring and electrolyte supplementation, accelerated refeeding may also be applied to achieve medical stabilization in extremely underweight adults with AN without increasing the risk of RS.

Assessment of Physical Activity Patterns in Adolescent Patients with Anorexia Nervosa and Their Effect on Weight Gain.

(1) Background: Altered physical activity (PA) affects weight recovery in anorexia nervosa (AN) patients. The study aimed to objectively characterize PA patterns and their effect on weight trajectory in adolescent AN patients. (2) Methods: PA was assessed in 47 patients on admission to inpatient treatment, in n = 25 of these patients again 4 weeks after discharge (follow-up, FU), as well as in 20 adolescent healthy controls using the Sense Wear™ armband. The following PA categories were defined by metabolic equivalent (MET) ranges: sedentary behavior (SB), light (LPA), moderate (MPA), vigorous (VPA), and high-level PA (HLPA= MPA + VPA). (3) Results: LPA on admission was significantly higher in AN patients than in controls (103 vs. 55 min/d, p < 0.001), and LPA in AN decreased over time to 90 min/d (p = 0.006). Patients with higher admission LPA (n = 12) still had elevated LPA at FU (p = 0.003). High admission LPA was associated with a higher inpatient BMI percentage gain (ΔBMI%; 18.2% ± 10.0% vs. 12.0% ± 9.7%, p = 0.037) but with a loss of ΔBMI% at FU (-2.3% ± 3.6% vs. 0.8% ± 3.6%, p = 0.045). HLPA at baseline was associated with a lower inpatient ΔBMI% (p = 0.045). (4) Conclusion: Elevated LPA in AN patients decreased after inpatient treatment, and PA patterns had an impact on weight trajectory.

The Role of Objectively Measured, Altered Physical Activity Patterns for Body Mass Index Change during Inpatient Treatment in Female Patients with Anorexia Nervosa.

Increased physical activity (PA) affects outcomes in patients with anorexia nervosa (AN). To objectively assess PA patterns of hospitalized AN patients in comparison with healthy, outpatient controls (HC), and to analyze the effect of PA on Body Mass Index (BMI) change in patients with AN, we measured PA in 50 female patients with AN (median age = 25 years, range = 18⁻52 years; mean BMI = 14.4 ± 2.0 kg/m²) at the initiation of inpatient treatment and in 30 female healthy controls (median age = 26 years, range = 19⁻53 years; mean BMI = 21.3 ± 1.7 kg/m²) using the SenseWear™ armband. Duration of inpatient stay and weight at discharge were abstracted from medical records. Compared with controls, AN patients spent more time in very light-intensity physical activity (VLPA) (median VLPA = 647 vs. 566 min/day, p = 0.004) and light-intensity physical activity (LPA) (median LPA = 126 vs. 84 min/day, p < 0.001) and less time in moderate-intensity physical activity (MPA) (median MPA = 82 vs. 114 min/day, p = 0.022) and vigorous physical activity (VPA) (median VPA = 0 vs. 16 min/day, p < 0.001). PA and BMI increase were not associated in a linear model, and BMI increase was mostly explained by lower admission BMI and longer inpatient stay. In a non-linear model, an influence of PA on BMI increase seemed probable (jack knife validation, r² = 0.203; p < 0.001). No direct association was observed between physical inactivity and BMI increase in AN. An altered PA pattern exists in AN patients compared to controls, yet the origin and consequences thereof deserve further investigation.

Metabolic Barriers to Weight Gain in Patients With Anorexia Nervosa: A Young Adult Case Report.

Background: Over-proportionally high energy requirements in some patients with anorexia nervosa (AN) have been reported, but their exact origin remains unclear. Objective: To objectively measure metabolic alterations in an AN patient with high energy requirements as judged by clinical observation. Materials and Methods: We present the case of a young woman with AN (index patient, IP; 19 years, admission BMI 13.9 kg/m2). After 3 months of treatment at BMI 17.4 kg/m2, we assessed her resting energy expenditure (REE), respiratory exchange ratio (RER), diet-induced thermogenesis (DIT), seated non-exercise physical activity (NEPA in Volt by infrared sensors), and exercise activity thermogenesis (EAT) in a metabolic chamber; body composition (bioimpedance analysis), energy intake (15d-food protocol), physical activity (accelerometry) and endocrine parameters. The IP was compared for REE, RER, DIT and seated NEPA to six AN patients (AN-C) and four healthy women (HC-1), and for EAT to another six healthy women (HC-2). Results: Our IP showed high REE (110% of predicted REE according to Harris & Benedict) and high seated NEPA (47% increase over AN-C, 40% over HC-1), whereas DIT (IP: 78 vs. HC-1: 145 ± 51 kJ/180 min) and EAT (IP: 157 vs. HC-2: 235 ± 30 kJ/30 min) were low, when compared with HC. The other AN patients showed a lower REE (AN: 87 ± 2% vs. HC: 97 ± 2% predicted) at increased DIT (AN: 187 ± 91 vs. HC: 145 ± 51 kJ/180 min) when compared with HC. RER of the IP was low (IP: 0.72 vs. 0.77 in AN-C; 0.77 in HC-1 and 0.80 in HC-2). Conclusions: Complex and variable disturbances of energy metabolism might exist in a subgroup of patients with AN during refeeding, which could lead to unexpectedly high energy requirements. Future studies need to confirm the existence, and investigate the characteristics and prevalence of this subgroup. Clinical trial Registry number: NCT02087280, https://www.clinicaltrials.gov/.

Incomplete total body protein recovery in adolescent patients with anorexia nervosa.

Background: Bone health and growth during adolescence require adequate total body protein (TBPr). Renutrition for patients with anorexia nervosa (AN) should aim to normalize body composition and to recover both fat mass and TBPr. Objective: We intended to analyze predictors of protein status, including exercise status, in adolescents with AN and to investigate whether weight gain would replenish body protein deficits. Methods: We assessed TBPr in a longitudinal, observational study as height-adjusted nitrogen index (NI) using in vivo neutron activation analysis in 103 adolescents with AN [mean ± SD age, 15.6 ± 1.4 y; body mass index (BMI, in kg/m2), 16.5 ± 1.6] at the commencement of inpatient refeeding (T0), in 56 of these patients 7 mo thereafter as outpatients (T1), and in age-matched controls (C; n = 51, 15.5 ± 2.1 y, BMI 20.7 ± 1.9). Lean tissue and fat mass were assessed by dual-energy X-ray absorptiometry. BMI, BMI standard deviation score, and lean tissue mass were tested as predictors of protein status using receiver operating characteristic analysis. Results: At T0, NI was decreased in AN (AN, 0.88 ± 0.10 compared with C, 1.00 ± 0.08, P < 0.001). In 34%, the patients showed protein depletion. Patients classified as ``exercisers'' had a higher NI than did ``nonexercisers'' (0.89 ± 0.11 compared with 0.85 ± 0.08, P = 0.045). BMI, BMI standard deviation score, and lean tissue mass did not show potential as predictors of protein status. Despite increases in weight (+6.9 ± 4.5 kg), and BMI (+2.5 ± 1.7), protein status did not improve (TBPr T0, 8.0 ± 1.1 kg; T1, 8.1 ± 1.0 kg, P = 0.495). In an AN subgroup at 7 mo matched with controls in age (AN, 16.5 ± 1.1 y; C, 16.2 ± 1.8 y) and BMI (AN, 20.5 ± 1.4; C, 20.7 ± 1.3), protein status was still not normalized in AN (NI: AN, 0.89 ± 0.09 compared with C, 1.00 ± 0.07, P < 0.001). Conclusions: Adolescents recovering from AN remained protein depleted at 7 mo after baseline assessment, even though they were weight restored.

Is hypercortisolism in anorexia nervosa detectable using hair samples?

Anorexia nervosa (AN) is a severe mental disorder accompanied by extensive metabolic and endocrine abnormalities. It has been associated with hypercortisolism using short-term measurement methods such as 24 h-urine, saliva, and blood. The aim of this study was to examine whether the proposed hypercortisolism in acutely underweight AN (acAN) is also reflected in a long-term measure: hair cortisol (HCC). To gain further insight, we compared hair cortisol to a well-established classical cortisol measure (24 h-urine; UCC) longitudinally in acAN. Hair samples were collected and analyzed using a LC-MS/MS-based method to provide a monthly cortisol value. We compared HCC in samples of 40 acAN with 40 pairwise age-matched healthy controls (HC) as well as 23 long-term recovered AN participants (recAN) with 23 pairwise age-matched HC (cross-sectional design). In the second part, UCC collected weekly during 14 weeks of weight-restoration therapy in 16 acAN was compared with the (time-corresponding) HCC using linear mixed models and bivariate correlations (longitudinal design). No group differences in HCC occurred comparing acAN and recAN to HC (cross-sectional study). The longitudinal analysis revealed a decrease of UCC but not HCC with weight gain. Furthermore, there was no overall significant association between UCC and HCC. Only in the last four weeks of weight-restoration therapy we found a significant moderate correlation between UCC and HCC. HCC did not reflect the expected hypercortisolism in acAN and did not decrease during short-term weight-restoration. Time-corresponding measurements of UCC and HCC were not consistently associated in our longitudinal analysis of acAN undergoing inpatient treatment. Given the drastic metabolic disturbances in acutely underweight AN our findings could be interpreted as disturbed cortisol incorporation or altered activity of 11-ß-HSD-enzymes in the hair follicle.

Leptin and Physical Activity in Adult Patients with Anorexia Nervosa: Failure to Demonstrate a Simple Linear Association.

High physical activity (PA) in patients with anorexia nervosa (AN) is hypothesized to be, at least in part, a consequence of hypoleptinemia. However, most studies on the association of leptin and PA in AN were performed in adolescents or young adults, and PA was generally measured with subjective tools. We aimed to explore the association of leptin and PA in adults with AN using an objective technique to quantify PA. Using a cross-sectional, observational design, we analyzed body fat (bioelectrical impedance), PA (accelerometry, SenseWear™ armband) and plasma leptin (ELISA) in 61 women with AN (median age: 25 years, range: 18-52 years; median BMI: 14.8 ± 2.0 kg/m²) at the start of hospitalization. Results indicated a mean step count per day of 12,841 ± 6408 (range: 3956-37,750). Leptin was closely associated with BMI and body fat (ρ = 0.508 and ρ = 0.669, p < 0.001), but not with steps (ρ = 0.015, p = 0.908). Moreover, no significant association was observed between BMI and steps (ρ = 0.189, p = 0.146). In conclusion, there was no simple, linear association of leptin and PA, highlighting the need for more complex and non-linear models to analyze the association of leptin and PA in adults with AN in future studies.

Plasma kisspeptin and ghrelin levels are independently correlated with physical activity in patients with anorexia nervosa.

While physical hyperactivity represents a frequent symptom of anorexia nervosa and may have a deleterious impact on the course of the disease, the underlying mechanisms are poorly understood. Since several food intake-regulatory hormones affect physical activity, the aim of the study was to investigate the association of physical activity with novel candidate hormones (kisspeptin, ghrelin, oxyntomodulin, orexin-A, FGF-21, R-spondin-1) possibly involved in patients with anorexia nervosa. Associations with psychometric parameters and body composition were also assessed. We included 38 female anorexia nervosa inpatients (body mass index, BMI, mean ± SD: 14.8 ± 1.7 kg/m2). Physical activity was evaluated using portable armband devices, body composition by bioelectrical impedance analysis. Blood withdrawal (hormones measured by ELISA) and psychometric assessment of depressiveness (PHQ-9), anxiety (GAD-7), perceived stress (PSQ-20) and disordered eating (EDI-2) were performed at the same time. Patients displayed a broad spectrum of physical activity (2479-26,047 steps/day) which showed a negative correlation with kisspeptin (r = -0.41, p = 0.01) and a positive association with ghrelin (r = 0.42, p = 0.01). The negative correlation with oxyntomodulin (r = -0.37, p = 0.03) was lost after consideration of potential confounders by regression analysis. No correlations were observed between physical activity and orexin-A, FGF-21 and R-spondin-1 (p > 0.05). Kisspeptin was positively correlated with BMI and body fat mass and negatively associated with the interpersonal distrust subscale of the EDI-2 (p < 0.01). Depressiveness, anxiety, and perceived stress did not correlate with kisspeptin or any other of the investigated hormones (p > 0.05). In conclusion, kisspeptin is inversely and ghrelin positively associated with physical activity as measured by daily step counts in anorexia nervosa patients suggesting an implication of these peptide hormones in the regulation of physical activity in anorexia nervosa.

Evaluation of a Portable Armband Device to Assess Resting Energy Expenditure in Patients With Anorexia Nervosa.

BACKGROUND: In women with anorexia nervosa (AN), resting energy expenditure (REE) is decreased due to reduced energy intake and severe underweight. The assessment of REE allows estimating individual metabolic downregulation and better understanding body weight regulatory mechanisms in severely underweight patients with AN. However, REE predictive equations are known to have considerable shortcomings in patients with AN. Our aim was to evaluate a portable armband device (SenseWear armband [SWA]; BodyMedia, Inc, Pittsburgh, PA) for the assessment of REE against the measurement with indirect calorimetry (IC) as the reference method. METHODS: We assessed REE simultaneously by IC and SWA in 50 women with AN at the start of inpatient therapy and calculated REE using 2 predictive equations. RESULTS: Reliable data for IC measurement were obtained for 34 patients (age: 27.0 ± 8.0 years; body mass index: 14.4 ± 2.0 kg/m²). REE assessed with SWA was overestimated by 23% ± 27% compared with REE measured by IC (1166 ± 174 vs 979 ± 198 kcal/d, P < .001). REE estimation with SWA gave an accurate prediction within 10% deviation of REE measured with IC in 35% of the patients. In contrast, REE calculated with 2 predictive equations underestimated REE measured with IC by -26% ± 17% and -5% ± 20%, respectively. CONCLUSIONS: A mean difference of 187 kcal/d between both techniques for the assessment of REE may be of methodological relevance. Therefore, SWA and IC are not interchangeable methods for the assessment of REE in underweight females with AN.