Refeeding Process Research Articles

Atypical antipsychotic use does not impact weight gain for individuals with extreme anorexia nervosa: a retrospective case–control study

BackgroundThere are no U.S. Food and Drug Administration (FDA)-approved medications for the treatment of anorexia nervosa (AN). Various medication classes have been evaluated for benefits in this population, including antipsychotics. Studies focused on use of antipsychotics for assistance with weight restoration in AN produced conflicting results. While current evidence does not suggest that antipsychotic medications can be generally recommended for persons with AN, some individuals might benefit from an antipsychotic medication for anxiety, mood, and the cognitive distortions that accompany the illness. It is well-established that atypical antipsychotics can cause weight gain when taken by other psychiatric populations. This published data can understandably limit the willingness of persons with AN to trial these medications. Given the conflicting results of studies examining antipsychotic-related weight gain in AN, it is currently hypothesized that individuals with extreme anorexia nervosa, restricting type, do not experience the weight gain seen in other psychiatric populations utilizing atypical antipsychotics.MethodsTwo hundred seventy-six individuals with extreme AN were enrolled in this retrospective, case–control study between April 1, 2016 and June 30, 2022 utilizing study-specific inclusion and exclusion criteria. Clinical and demographic data, including use of atypical antipsychotics and weights, were retrospectively obtained from chart review. Variables were assessed for normality using univariate statistics. Continuous variables were described using means (M) and standard deviations (SD) or medians and interquartile ranges (IQR) based on normality. Differences in weight gain between cohorts was ascertained via independent samples t-test. P values of < 0.05 were considered statistically significant, and all analyses were completed using SAS Enterprise Guide software version 7.1 (SAS Institute, Cary, NC) and R version 4.3.1 (R Core Team, 2023).ResultsUse of antipsychotics in this population of individuals with extreme AN did not impact the rate of weight gain (M: 1.7 kg/week, SD: 0.9 and 0.8, for cases and controls respectively).ConclusionsWeight gain is often cited by individuals with AN as a feared side effect of antipsychotic medications. In this study, there was no difference in weight trends for individuals taking atypical antipsychotic medications during the refeeding process compared with individuals who were not.

Change and Regulation of Nutritional Metabolism in Silver Pomfret During Compensatory Growth.

Compensatory growth (CG) in fish is heavily influenced by nutrient metabolism. However, there are limited studies examining how nutrient metabolism is regulated during this process. For silver pomfret, an important commercial marine fish, it's crucial to establish effective starvation and re-feeding strategies to ensure good water quality and fast growth. To identify the complete compensatory growth model of silver pomfret, we conducted an experiment with a control group (normal feeding) and three starvation/re-feeding groups. We observed that the recovery of weight and condition factor in the 14-day starvation and 14-day re-feeding groups was significantly faster than other groups, indicating full compensatory growth. Thus, we selected this group for the next experiment. We performed untargeted metabolomics and transcriptome analysis of muscle tissue on Day 14, 21 and 28 (CG process), and examined the key regulatory genes of nutrient metabolism on Day 0, 7, 14, 21 and 28 (starvation and re-feeding process). Our data revealed that during starvation, silver pomfret first utilized carbohydrates and short-chain lipids, followed by proteins and long-chain lipids. After re-feeding, lipids accumulated first, resulting in rapid growth, followed by the recovery of protein content in muscle. During starvation, the expression of anabolic-related genes such as TER and CALR decreased, and catabolic-related genes such as TSC2 and MLYCD increased, promoting the AMPK pathway. During re-feeding, anabolic-related gene expression increased without AMPK inhibition. Our findings provide insights into the energy utilization strategies of fish and molecular regulation during compensatory growth in fish.

L’approccio nutrizionale nell’anoressia nervosa: dalla teoria alla pratica clinica

Anorexia nervosa is a common eating disorder characterized by a physical and psychosocial deterioration due to an altered pattern of food intake and weight control. The severity of malnutrition often requires hospitalization to start enteral artificial refeeding. The objective of this article is to review the scientific evidence about the refeeding process of malnourished inpatients with anorexia and to summarize up-to-date evidences, certainties, doubts and new proposals. Moreover, it gives advice and suggests strategies to manage malnutrition in the clinical practice.

63 Influence of diet and body condition on blood chemistry and body composition during the refeeding process

Starved horses with low body condition scores (BCS, < 3 out of 9) continues to be a prominent welfare concern, yet limited nutritional studies on the reconditioning process exist. The aim of this study was to determine how alternative diets affected blood chemistry panels and body composition in mature, starved (initial BCS 1 or 2) light breed horses during the refeeding process (final BCS 4, UTK IACUC 2811–1220). Horses (n = 10, 18.8 ± 2.5 y (mean ± SD), BCS 1.4 ± 0.5, 3 geldings and 6 mares, light breeds) were placed on a control diet (C; 100% digestible energy, DE, from grass hay and Purina Free Balance) or a concentrate diet (S; 50 % DE from grass hay and 50% DE from Purina Equine Senior). Diets were formulated to increase caloric intake in accordance with previously established refeeding recommendations and the NRC (2007), where horses were increased from 50% DE to 100% DE over 10 d to prevent refeeding syndrome, and then were increased up to 145% DE as needed based on weekly body weight (BW) until a BCS of 4 was reached. Weekly BW and BCS were assessed by 3 independent reviewers and plasma samples collected at each BCS increase based on reviewer average and an increase in of 16–20 kg in BW. Diet and BCS effects on blood chemistry and body composition were analyzed using generalized linear mixed models in SAS, with breed and individual animals as random effects, and mean separation using Tukey's adjustment.Significance was detected at P < 0.05 (SAS 9.4, Cary, NC). Non-normally distributed data were rank transformed as determined by Shapiro-Wilk. Of the 10 horses in the study, 3 were euthanized within 10d of enrollment due to infectious disease or colic unassociated with dietary treatment, 1 was disenrolled due to pneumonia, and the remaining 6 horses were fully reconditioned (C: n = 3, S: n = 3). Horses were recovered similarly between diet groups (change in BW: C = 46.15 ± 9.9 kg, S = 41.8 ± 14.9 kg, mean ± SD, P > 0.05). Plasma creatine kinase differed by BCS (P = 0.0007), whereas creatinine differed by both diet (P = 0.006) and BCS (P < 0.0001); however, all values were within normal limits. Lactose was lower in BCS 4 horses compared with all other scores, yet all values were also within normal ranges (P = 0.0007). Rib fat thickness was greater in BCS 4 horses (C = 0.35(0.08)mm, S = 0.38(0.20)mm, median(IQR)) than all other BCS (P = 0.001). Rump fat thickness was highest in BCS 4 horses (S = 0.36 (0.13), C = 0.30 (0.05)). Based on our findings, grass hay and complete feed concentrates can be used to successfully recover emaciated horses. Further studies would be helpful in determining optimal refeeding protocols.

Metabolomic Profiles in Starved Light Breed Horses during the Refeeding Process.

Simple SummaryUnwanted horses and other equids continue to be a global issue throughout which the prevalence of malnourished equids persists as a welfare concern. Nutritional studies evaluating the refeeding or rehabilitation process are limited, and little data exists to explain how metabolic function changes during refeeding. Therefore, the objective of this study was to assess changes in metabolite profile (metabolome) of emaciated horses throughout rehabilitation via refeeding. Horses were fed specific diets over the rehabilitation period, and blood samples were collected and analyzed throughout. Comparison of equine within a malnourished state and equine during the refeeding process showed decreases in potentially toxic chemical compounds related to liver, kidney, and muscle function as well as shifts related to changing energy demands. This study concludes that the refeeding and rehabilitation process results in an overall change in the equine metabolome.The large population of emaciated horses continues to be an issue troubling the equine industry. However, little is known regarding the collection of equine metabolites (metabolome) during a malnourished state and the changes that occur throughout nutritional rehabilitation. In this study, ten emaciated horses underwent a refeeding process, during which blood samples were collected for a blood chemistry panel and metabolomics analysis via ultrahigh performance liquid chromatography–high resolution mass spectrometry (UHPLC-HRMS). Significant differences among blood chemistry analytes and metabolite abundance during the critical care period (CCP; Days 1–10 of rehabilitation) and the recovery period (RP; the remainder of the rehabilitation process) were observed. Potentially toxic compounds, analytes related to liver, kidney, and muscle function, as well as energy-related metabolites were altered during the refeeding process. The combination of blood chemistry and metabolomics analyses on starved equine during rehabilitation provide vital biological insight and evidence that the refeeding process has a significant impact on the equine metabolome.

Impact of calorie intake and refeeding syndrome on the length of hospital stay of patients with malnutrition: a systematic review and meta-analysis

The decrease of nutritional status has affected one-third hospitalized patients, while there is no widely used definition of malnutrition. Refeeding syndrome is a severe complication of refeeding in people with malnutrition, it includes a series of electrolyte disorders and clinical symptoms. Further research is warranted to determine whether refeeding syndrome prolongs the length of stay, and to verify the effect of different energy intakes during refeeding on the length of stay in people with malnutrition. Our review aimed to explore the effects of refeeding syndrome and initial calorie intake on the length of stay in patients with malnutrition. This study aids the understanding of clinical nutrition strategies to prevent and treat refeeding syndrome. PubMed, Embase, Cochrane Library, Web of Knowledge, and two Chinese databases were systematically searched until October 2021. Controlled studies of patients' refeeding process with the outcome of length of stay were included. Effect sizes were expressed as 95% confidence intervals (CIs) and calculated using random-effects models. Eighteen studies involving 3868 participants were included in our review. The pooled length of stay of 2965 patients with refeeding syndrome in 11 studies was 25.55 (95% CI, 20.20-30.90) days. The pooled impact of refeeding syndrome on length of stay of 2634 patients in 10 studies was weighted mean difference (WMD)=2.91 (95% CI,-0.18 - 6.00; P=0.065) days. The pooled effect of higher calorie intake of 1234 patients in 8 studies was WMD=-3.04 (95% CI,-5.10 to-0.99, P=0.003) days. The average length of stay in patients with refeeding syndrome was 25.55 days with a very high heterogeneity between studies. Refeeding syndrome affects the length of stay in part of, but not all, patients. In the present review, we concluded that higher initial calorie intake may help shorten the length of stay in patients with malnutrition. More well-designed randomized controlled trials are needed to explore the effect of calorie intake during refeeding.

Five-Year Inpatient Management of Teenagers With Anorexia Nervosa: Focus on Nutritional Issues.

In patients with Anorexia Nervosa (AN) malnutrition can lead to life-long nutritional treatments. The refeeding process can combine natural feeding (NF) with specific nutritional strategies, including oral nutritional supplements (ONS) and nasogastric feeding (NGF). Aims of the present study were to assess the efficacy of hospital protocol and identify the most effective inpatient nutritional strategies for weight restoration. All patients hospitalized from April 2015 to April 2020 were enrolled. According to hospital protocol, NF was proposed to all patients; ONS were combined with NF if caloric intake was <70% of the requirements and NGF was added if caloric intake did not reach 30% in the first week from admission. Overall, 186 patients [M = 20; median age 14 (interquartile range 1316)] were included. Nutritional issues were the main indication to admission (56.6%). A significant effect of combination treatment, with a shorter duration of hospitalization when using ONS with NGF in addition to NF was found (ß: -20.28 [95% confidence interval -34.92:-5.65], P < 0.001). Only one patient showed a significant but limited increase of liver enzymes. We provide a safe and effective standardized protocol to treat the malnutrition of teenagers with AN in an inpatient setting. Malnutrition was the most important cause of admission, and more than half of the patients admitted were severely malnourished. The combination of NF, ONS, and NGF was the most effective strategy to achieve the weight restoration; however, this result should be validated on larger series of patients treated with NGF and NF.

Anorexia nervosa and pancreatitis.

Acute pancreatitis is a condition whereby erroneous activation of trypsin and zymogen results in pancreatic autodigestion. There are many aetiologies, with alcohol intake and gallstones being the most common. Anorexia nervosa is an eating disorder in which patients' reduced food intake and psychological aversion of weight gain can result in low body weight and malnourishment. The link between pancreatitis and anorexia nervosa is not well understood; this article explores the theorised pathophysiology connecting the two conditions, as well as the optimal management of patients when the conditions co-exist based on current literature. A literature search was performed using MEDLINE, EMBASE and CINAHL databases for all journal articles on the topic of presentations of acute or chronic pancreatitis in adults with anorexia nervosa. The literature proposes various links between anorexia nervosa and pancreatitis. It is theorised that pancreatitis may arise as a result of malnourishment itself or secondary to the refeeding process. Some explanations focus on the histopathological changes to the pancreas that malnourishment induces, while others focus on the enzymatic changes and oxidative damage that arise in the malnourished state. More mechanical mechanisms such as gastric dilatation, gastrointestinal ileus and compartmental fluid shift during refeeding have also been proposed as explanations for the link between the conditions. Some medications used in the management of anorexia nervosa have also been linked to pancreatitis.

Impact of Refeeding Syndrome on Short- and Medium-Term All-Cause Mortality: A Systematic Review and Meta-Analysis

BackgroundThe refeeding syndrome has been described as a potentially life-threatening complication of renutrition. However, moving from single reports to larger population studies, the real impact of refeeding syndrome on all-cause mortality is still unknown. MethodsPubMed/Medline, EMBASE, Cochrane library, and CINAHL databases were systematically searched until September 2020 for studies reporting mortality rates in patients who developed the syndrome at renutrition compared with those who did not develop it. Effect sizes were pooled through a random-effect model. ResultsThirteen studies were finally considered in the meta-analysis, for a total of 3846 patients (mean age 64.5 years; 58% males). Pooled data showed a nonsignificant trend toward an increased short-term (≤1 month) mortality in patients developing the refeeding syndrome (odds ratio = 1.27, 95% confidence interval 0.93-1.72), mostly driven by studies in which renutrition was not prescribed and supervised by a nutritional support team (P = .01 at subgroup analysis) and by studies published in previous years (P = .04 at meta-regression). When examining medium-term (≤6 month) mortality, an overall statistical significance toward higher risk was observed (odds ratio = 1.54, 95% confidence interval 1.04-2.28). ConclusionThis was the first meta-analysis that specifically assessed the impact of refeeding syndrome on mortality. Our results suggested a nonsignificant trend toward increased mortality in the short term but a significantly increased mortality in the medium term. The supervision/management of the refeeding process by a nutrition specialist might be a key factor for the limitation of this mortality excess.

Intensive Treatments in Adolescent Anorexia Nervosa.

Approximately one-fifth to one-third of patients with adolescent anorexia nervosa (AN) need intensive care in the course of their illness. This article provides an update and discussion on different levels of intensive care (inpatient treatment (IP), day patient treatment (DP) and home treatment (HoT)) in different health care systems based on recently published literature. Important issues discussed in this article are new recommendations for the refeeding process and the definition of target weight as well as principles of medical stabilization and psychotherapeutic approaches. The pros and cons of longer or shorter hospitalization times are discussed, and the advantages of stepped care and day patient treatment are described. A new promising intensive treatment method involving the patient, their caregivers and the direct home environment is introduced. Parents and caregivers should be included in treatment research to foster collaborative work with the attending clinicians. There is an urgent need to evaluate the mid- to long-term outcomes of various intensive treatment programs to compare their effectiveness and costs across different health care systems. This could help policy makers and other stakeholders, such as public and private insurances, to enhance the quality of eating disorder care.

The relationship between weight change and C3 complement levels in patients with anorexia nervosa

Objective: Anorexia Nervosa (AN) affects the entire body with serious medical conditions and has the highest mortality rates in any psychiatric disorder. These medical abnormalities are reversible after weight gain and resolution of the underlying anorectic state. The role of the immune system in the development and maintenance of AN is apparently underestimated. Changes in the complement system, particularly C3 in AN, are not well understood. This study was designed to evaluate changes in body weight and complement C3 levels. Method: This study was designed as a prospective study on 12 female AN patients. Serum samples were taken biweekly for 4 times. The serum levels of complement C3 levels were quantified and correlated with the body mass index (BMI). Repeated measures of ANOVA were used to determine changes in BMI and C3 complement levels. A generalized estimating equation (GEE) analysis was used to determine the relationship between BMI and complement C3 levels over time. Results: An increase in C3 levels was observed in the analysis of the data according to the increase in body weight of the patients as a result of eating of AN patients. There was a significant increase in C3 levels (p=0.042) and BMI levels of the patients (p=0.01). The increase in BMI was followed by the increase in C3 level. BMI increases over time were statistically correlated with changes in C3 levels. Conclusion: Increasing C3 levels with increasing BMI during the treatment process are parallel. Complement ‘C3’ serum levels potentially serving as a guide for monitoring the refeeding process also could be a useful marker for determining and monitoring the treatment success in AN.

Identification, characterization, and expression profiles of insulin-like peptides suggest their critical roles in growth regulation of the Pacific oyster, Crassostrea gigas.

The insulin/insulin-like growth factor signaling (IIS) pathway is well-known in regulation of cell growth and proliferation in vertebrates, while its role in invertebrates such as mollusks remains largely unknown. In this study, we performed an extensive multi-omics data mining and identified four insulin-like peptide genes, including ILP, MIRP3, MIRP3-like and ILP7, in the Pacific oyster, Crassostrea gigas. Their potential roles in growth regulation were further investigated using the selectively bred fast-growing C. gigas variety "Haida No.1". Expression profiling and in situ hybridization of these insulin-like peptides suggested their distinct tissue-specific expression pattern, with dominant expression in the neural enrichment tissues such as labial palp, visceral ganglia, adductor muscle, and digestive gland. The expressions of insulin-like peptides were significantly altered by food abundance in a gene-specific fashion. The expression of ILP was reduced during fasting and increased after re-feeding, the expressions of MIRP3 and ILP7 were generally induced during fasting and down-regulated after re-feeding, while the expression of MIRP3-like was firstly up-regulated and then down-regulated during the fasting and re-feeding process. Furthermore, the expressions of all four insulin-like peptide genes were significantly suppressed at low temperature, in accordance with the growth inhibition. These results indicated that all four insulin-like peptides would play critical but different roles in regulation of growth in the oysters. This work provides valuable information for further investigation on growth regulation mechanism in mollusks and molecular assisted breeding of growth with other production traits in the Pacific oyster.

Severe Calorie Restriction Induces Gut Microbiota-Dependent Intestinal Stem Cell Dysfunction

Abstract Objectives Anorexia nervosa (AN) is a life-threatening illness, primarily characterized by extreme calorie restriction (CR). Given the substantial undernourishment in patients with AN, it is essential to understand the effects of severe CR on the small intestinal epithelium which is the primary tissue responsible for nutrient absorption and is therefore critical for the refeeding process. While we have previously reported that patients with AN harbor an altered intestinal microbiota, it remains unknown whether an AN-associated gut microbial community, induced by a nutrient-deprived environment, impacts intestinal epithelial physiology. Methods Conventionally-raised (CONVR) and germ-free (GF) mice were individually housed and placed on a 60% CR (60CR) diet for 9 days. CONVR mice were housed in standard specific-pathogen free conditions while GF mice were bred and housed in sterile isolators to occlude exposure to microorganisms. Mice were injected intraperitoneally with 4 mg/kg 5-ethynyl-2’deoxyuridine (EdU) 90 minutes before necropsy to mark proliferating cells. Intestinal tissue was collected for histology and intestinal crypts were isolated for ex vivo organoid culture. Results CONVR and GF mice on a 60CR diet lost significant body weight (28%±1 and 24%±1, respectively). 60CR CONVR and GF mice both displayed a significant increase in ISCs (+1.27 ± 0.02-fold and + 1.15 ± 0.05-fold, respectively) yet a significant decrease in proliferating cells (1.7 ± 0.2-fold and 1.7 ± 0.1-fold, respectively) compared to ad libitum controls. Interestingly, ex vivo organoids derived from crypts of CONVR 60CR mice were significantly smaller compared to organoids yielded from control crypts, but, strikingly, no differences in organoid size were observed between GF crypts from either diet group. Conclusions While ISC from 60CR CONVR and GF mice exhibited similar features, 60CR GF ISC function was maintained as indicated by the similar organoid growth relative to GF ad libitum controls. These data suggest that severe CR induces ISC dysfunction resulting in impaired de novo generation of digestive epithelial mass, and that these changes are microbiota-dependent. Funding Sources National Institutes of Health, North Carolina Translational and Clinical Sciences Institute, NCSU College of Veterinary Medicine, UNC Center for Gastrointestinal Biology and Disease.

Safety and efficacy of mucous fistula refeeding in low-birth-weight infants with enterostomies.

To investigate the safety and efficacy of mucous fistula refeeding (MFR) in low-birth-weight infants. Between December 2006 and December 2018, medical records of low-birth-weight infants who underwent small bowel enterostomy formation in the neonatal period and subsequent stoma closure at our institution were retrospectively reviewed. Patients were assigned to "refeeding" (RF) and "non-refeeding" (NRF) groups, which were compared for patient characteristics and clinical outcomes. We also cultured the proximal stoma output over time in the RF group and reviewed changes in the flora to evaluate the safety of refeeding. In the RF group, compared with that before refeeding, there was significantly more rapid weight gain after refeeding (17.7 vs 10.6g/day; P = 0.002). Median total time of parenteral nutrition (PN) was 25 and 87days in the RF and NRF groups, respectively (P = 0.001). The number of patients who developed PN-associated liver disease (PNALD) was smaller in the RF group (P = 0.12). No complications of MFR were noted and no pathogenic bacteria were cultured. MFR was able to diminish the need for PN, which potentially decreased the incidence of PNALD, and was safe as there were no complications of the refeeding process.

Nutritional Management and Outcomes in Malnourished Medical Inpatients: Anorexia Nervosa.

Background: Anorexia Nervosa (AN) is a psychiatric disorder characterised by a physical and psychosocial deterioration due to an altered pattern on the intake and weight control. The severity of the disease is based on the degree of malnutrition. The objective of this article is to review the scientific evidence of the refeeding process of malnourished inpatients with AN; focusing on the clinical outcome. Methods: We conducted an extensive search in Medline and Cochrane; on April 22; 2019; using different search terms. After screening all abstracts; we identified 19 papers that corresponded to our inclusion criteria. Results: The article focuses on evidence on the characteristics of malnutrition and changes in body composition; energy and protein requirements; nutritional treatment; physical activity programmes; models of organisation of the nutritional treatment and nutritional support related outcomes in AN patients. Conclusion: Evidence-based standards for clinical practice with clear outcomes are needed to improve the management of these patients and standardise the healthcare process.

Understanding and addressing eating disorders

Eating disorders include conditions such as excessive and unhealthy reductions in food intake or overeating, distress, and overuse of body shape and weight. Some of the most recognizable among society are anorexia nervosa, bulimia nervosa, binge eating and orthorexia. Eating disorders are very often diagnosed at a late stage of the disease and curability is quite difficult. A multidisciplinary approach and lifelong efforts are needed in order to address such conditions. The psychology of eating disorders has been widely studied over the years. However, very few guidelines address the re-feeding process of the people involved. This review focuses on the nutritional point of view of eating disorders and can be a valuable addition to treatment of these serious conditions.

SU44 - CORRELATION BETWEEN GENE EXPRESSION CHANGE AND HORMONE CHANGE DURING REFEEDING IN ANOREXIA NERVOSA

Background Anorexia Nervosa (AN) is an eating disorder characterized by extreme food restriction, resulting in a body weight that is less then minimally expected. Genetic factors contribute to its etiology with heritability estimates ranging between 48%-74%. The first genome-wide significant locus for AN has been identified, and AN shows moderate and significant genetic correlations with additional psychiatric and somatic phenotypes. Transcriptome expression profiling has also been applied to AN to assess whether gene expression levels change with AN treatment. One study completed whole transcriptome expression profiling and compared expression levels at hospital admission and discharge. Sixty-seven genes were significantly differentially expressed. Similarly, other biological factors change during the treatment process for AN. Norepinephrine and ghrelin levels decrease with weight gain whereas adiponectin, estradiol, and glucose increase. It is unclear how changes in gene expression are associated with changes in other biological factors during weight gain—which we examine here. Methods Change in gene expression from inpatient admission (T1) to discharge (T2) has been previously identified. We explore associations between the top 10 differentially expressed genes and change in appetite (leptin, ghrelin) and reproductive hormones (estradiol), an inflammatory marker (TNF-α), and glucose. Subjects were 6 females receiving treatment for AN. Blood samples were taken at T1 and T2; a PAXgene tube used to collect blood for RNA. 12 samples were sequenced using 1 μg of total RNA as input. Samples were randomized and sequencing libraries prepared using Illumina TruSeq RNA Sample Preparation Kit v2. Libraries were quantitated using fluorometry and samples were pooled at equimolar concentrations prior to sequencing. Two lanes of Illumina HiSeq. 2000 generated a total of 381million 100 bp paired-end reads. Following quality control, we used a standard RNAseq alignment and analysis pipeline. A difference score (T2- T1) was created for the variables to explore the association between gene expression change and change in other biological factors. Results The top 10 previously identified differentially expressed genes included in this study: C16orf11, CYP11A1, DEFA10P, LINC00235, DSP, OLR1, CPA3, FMO3, AKAp12, and GATA2. Two significant correlations (p Discussion Change in CPA3 and GATA2 expression were positively associated with change in leptin. Little is known about the function of these genes. However, CPA3 is expressed in mast cells, which are immune cells contributing to the pathogenesis of obesity, diabetes, and other inflammatory diseases. GATA2 may be involved in dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency. In turn, leptin represents a link between nutritional status and immune response. Thus, factors that represent indirect makers of the body's immune and inflammation response appear to move in tandem during the refeeding process in AN. This aligns with work suggesting genetic overlap between AN, autoimmune disease, and markers of metabolic health. The genetic architecture of AN suggests it may be best conceptualized as both a metabolic disease and a psychiatric illness.

MECHANISMS IN ENDOCRINOLOGY: Anorexia nervosa and endocrinology: a clinical update.

Anorexia nervosa is a syndrome, that is collections of symptoms, which is not defined by its etiology. The severe cases are intractable. The syndrome is associated with multiple, profound endocrine alterations which may be adaptive, reactive or etiologic. Adaptive changes potentially may be inappropriate in clinical settings such as inpatient intensive re-nutrition or in a setting with somatic comorbidity. Electrolyte levels must be closely monitored during the refeeding process, and the need for weight gain must be balanced against potentially fatal refeeding complications. An important focus of clinical research should be to identify biomarkers associated with different stages of weight loss and re-nutrition combined with psychometric data. Besides well-established peripheral endocrine actions, several hormones also are released directly to different brain areas, where they may exert behavioral and psychogenic actions that could offer therapeutic targets. We need reliable biomarkers for predicting outcome and to ensure safe re-nutrition, however, first of all we need them to explore the metabolism in anorexia nervosa to open new avenues with therapeutic targets. A breakthrough in our understanding and treatment of this whimsical disease remains. Considering this, the aim of the present review is to provide an updated overview of the many endocrine changes in a clinical perspective.

Hepatic Complications of Anorexia Nervosa.

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.

Risk factors for elevated liver enzymes during refeeding of severely malnourished patients with eating disorders: a retrospective cohort study.

BackgroundThere are few previous reports regarding the cause and evolution of liver injury in patients with anorexia nervosa (AN) during the refeeding process, and its management remains controversial. This study aimed to determine the risk factors for elevated liver enzymes during refeeding and their effect on the therapeutic process in severely malnourished patients with eating disorders.MethodsIn a retrospective cohort study of 167 female inpatients in a single hospital from January 2004 to March 2015, 67 who had normal alanine aminotransferase (ALT) levels on admission were divided into two groups according to the presence or absence of elevated ALT levels during refeeding, and then compared.ResultsThe median age and body mass index (BMI) of the patients on admission were 22 [interquartile range (IQR), 16–33] years and 12.2 (IQR, 11.1–13.0) kg/m2, respectively. Compared with their cohorts, significantly more patients in the early onset age group (<15 years old) had elevated ALT levels during refeeding (67% vs. 33%, p = 0.033), as did patients with longer median time to nadir BMI (3.0 vs. 0 days, p = 0.03). In addition, onset age [odds ratio (OR): 0.274; 95% confidence interval (CI): 0.077–0.981; p = 0.047] and time to nadir BMI (OR: 1.271; 95% CI: 1.035–1.56; p = 0.022) were significantly associated with the odds of elevated ALT levels during refeeding.ConclusionsThe results of this study suggest that early age at onset may be a potential risk factor for elevated ALT levels during refeeding in severely malnourished patients with eating disorders. Furthermore, elevated ALT levels during refeeding were significantly associated with delay in the start of weight gain. No significant relationship was found between the amount of initial prescribed calories and elevated ALT levels during refeeding. The median time to maximum ALT was 27 (IQR, 21–38) days after the refeeding process started.Electronic supplementary materialThe online version of this article (doi:10.1186/s40337-016-0127-x) contains supplementary material, which is available to authorized users.