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1.  Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa 
Background
Fibroblast growth factor (FGF)23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN) patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23) in restricting-type AN (AN-R) patients, binge-eating/purging-type AN (AN-BP) patients, and healthy controls.
Methods
The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH)2D), and 25-hydroxyvitamin D (25-OHD) levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p < 0.017 was considered statistically significant.
Results
There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH)2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml) was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001), and the 1,25-(OH)2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml) than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015). No differences in plasma 25-OHD levels were observed among the groups.
Conclusion
This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH)2D levels.
doi:10.1186/1751-0759-2-10
PMCID: PMC2346464  PMID: 18412981
2.  Fibroblast growth factor 23 and parathyroid hormone after treatment with active vitamin D and sevelamer carbonate in patients with chronic kidney disease stage 3b, a randomized crossover trial 
BMC Nephrology  2012;13:49.
Background
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is secreted from bone and serum level increases as renal function declines. Higher levels of FGF23 are associated with increased mortality in hemodialysis-patients and in patients with chronic kidney disease (CKD) stage 2-4. The use of active vitamin D and phosphate binders as recommended in international guidelines, may affect the level of FGF23 and thereby clinical outcome. We investigated the effects of a phosphate binder and active vitamin D on the serum levels of intact FGF23 (iFGF23) and intact parathyroid hormone (iPTH) in patients with CKD stage 3b (glomerular filtration rate (GFR) 30–44 ml/min/1.73 m2).
Methods
Seven women and 14 men were included, mean age 65.6 ± 12.2 years. They were randomized in a 1:1 ratio to receive one of two treatment sequences. Group-1 (the alphacalcidol-sevelamer carbonate group): alphacalcidol 0.25 μg once daily for two weeks followed by sevelamer carbonate 800 mg TID with meals for two weeks after a two-week washout period. Group-2 (the sevelamer carbonate-alphacalcidol group): vice versa. Nineteen patients completed the study. The 25-hydroxyvitamin D level at baseline was 97.6 ± 25.0 nmol/l.
Results
There were no treatment effects on the iFGF23 and iPTH levels overall. In group-1 the iFGF23 level was higher after treatment with alphacalcidol compared with sevelamer carbonate (mean 105.8 ± 41.6 vs. 79.1 ± 36.5 pg/ml, p = 0.047 (CI: 0.4-52.9), and the iPTH level was lower (median: 26.5, range: 14.6-55.2 vs. median 36.1, range 13.4-106.9 pg/ml, p = 0.011). In group-2 the iFGF23 level increased non-significantly after treatment with sevelamer carbonate and throughout the washout period.
Conclusions
In this crossover trial with alphacalcidol and sevelamer carbonate in patients with CKD stage 3b, the levels of iFGF23 were not significantly different after the two treatments. However, in the group of patients initiating therapy with sevelamer carbonate the iFGF23 levels seemed to increase while this response was mitigated in the group of patients given alphacalcidol followed by sevelamer carbonate. This may have therapeutic implications on choice of first line therapy. The number of patients is small and this conclusion is in part based on subgroup analysis. It is therefore important that these results are confirmed in larger studies.
Trial registration
Trial Registration Number: European Clinical Trial Database (EudraCT) 2010-020415-36 and Clinical Trials.gov NCT01231438
doi:10.1186/1471-2369-13-49
PMCID: PMC3462711  PMID: 22742720
Active vitamin D; Chronic kidney disease; Fibroblast growth factor 23; FGF23; Phosphate-binder; Parathyroid hormone; PTH; Sevelamer carbonate
3.  FGF14 N-Terminal Splice Variants Differentially Modulate Nav1.2 and Nav1.6-Encoded Sodium Channels 
The Intracellular Fibroblast Growth Factor (iFGF) subfamily includes four members (FGFs 11–14) of the structurally related FGF superfamily. Previous studies showed that the iFGFs interact directly with the pore-forming (α) subunits of voltage-gated sodium (Nav) channels and regulate the functional properties of sodium channel currents. Sequence heterogeneity among the iFGFs is thought to confer specificity to this regulation. Here, we demonstrate that the two N-terminal alternatively spliced FGF14 variants, FGF14-1a and FGF14-1b, differentially regulate currents produced by Nav1.2-and Nav1.6 channels. FGF14-1b, but not FGF14-1a, attenuates both Nav1.2 and Nav1.6 current densities. In contrast, co-expression of an FGF14 mutant, lacking the N-terminus, increased Nav1.6 current densities. In neurons, both FGF14-1a and FGF14-1b localized at the axonal initial segment, and deletion of the N-terminus abolished this localization. Thus, the FGF14 N-terminus is required for targeting and functional regulation of Nav channels, suggesting an important function for FGF14 alternative splicing in regulating neuronal excitability.
doi:10.1016/j.mcn.2009.05.007
PMCID: PMC2832592  PMID: 19465131
4.  Iron and Obesity Status-Associated Insulin Resistance Influence Circulating Fibroblast-Growth Factor-23 Concentrations 
PLoS ONE  2013;8(3):e58961.
Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
doi:10.1371/journal.pone.0058961
PMCID: PMC3605441  PMID: 23555610
5.  Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial 
BMC Nephrology  2014;15:98.
Background
HS219 (40 mg chitosan-loaded chewing gum) is designed to bind salivary phosphorus as an add-on to available phosphorus binders. We performed a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of HS219 in hemodialysis (HD) patients with hyperphosphatemia as an add-on to phosphorus binders.
Methods
Sixty-eight HD patients who were maintained on calcium carbonate (n = 33) or sevelamer hydrochloride (n = 35) were enrolled. The primary end point was a change in serum phosphorus levels. Secondary end points included changes in levels of salivary phosphorus, serum calcium, parathyroid hormone (PTH), and intact fibroblast growth factor (iFGF) 23.
Results
Sixty-three patients chewed either HS219 (n = 35) or placebo (n = 28) for 30 min, three times a day, for 3 weeks. HS219 was well tolerated and safe. However, HS219 was not superior to placebo with additional reduction of serum phosphorus with respect to phosphorus binders at the end of the chewing period. There were no significant effects of HS219 on reduction of salivary phosphorus, serum calcium, iPTH, or iFGF23 levels.
Conclusions
The chitosan-loaded chewing gum HS219 does not affect serum and salivary phosphorus levels in Japanese HD patients with hyperphosphatemia. Our findings do not support previous findings that 20 mg of chitosan-loaded chewing gum reduces serum and salivary phosphorus levels.
Trail registration
ClinicalTrials.gov NCT01039428, 24 December, 2009.
doi:10.1186/1471-2369-15-98
PMCID: PMC4080692  PMID: 24968790
Chewing gum; Chitosan; Clinical trial; Hemodialysis; Hyperphosphatemia; Phosphorus binders
6.  The Serum Level of Fibroblast Growth Factor-23 and Calcium-Phosphate Homeostasis in Obese Perimenopausal Women 
Plasma FGF-23 concentrations and its relationship with calcium-phosphate homeostasis were evaluated in 48 perimenopausal obese women and in 29 nonobese controls. Serum parathyroid hormone, 25-hydroxyvitamin D3, CTX1, osteocalcin, total calcium, phosphorus, creatinine, and plasma intact FGF-23 concentrations were assessed. DXA of lumbar spine and femoral neck was performed to determine bone mineral density (BMD). Plasma iFGF-23 concentration was significantly higher in obese patients (by 42%) and correlated with age and BMD of proximal femur (R = −0.346; R = 0.285, resp.) but not with markers of bone turnover. However, serum phosphorus level in obese subjects was significantly lower. iFGF-23 concentration correlated significantly with body mass index (R = 0.292) and fat content (R = 0.259) in all study subjects. Moreover, a significant correlation between iFGF-23 and iPTH (R = 0.254) was found. No correlation between serum phosphorus or eGFR and plasma iFGF-23 and between eGFR and serum phosphorus was found. Elevated serum iFGF-23 concentration may partially explain lower phosphorus levels in the obese and seems not to reflect bone turnover.
doi:10.1155/2011/707126
PMCID: PMC3227462  PMID: 22164160
7.  Effects of milnacipran on binge eating – a pilot study 
Selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors are effective in the treatment of bulimia nervosa. There have been relatively few studies of the efficacy of specific serotonin and norepinephrine reuptake inhibitors in the treatment of eating disorders. Twenty-five outpatients with binge eating episodes, diagnosed as anorexia nervosa, binge-eating/purging type, bulimia nervosa/purging type, or bulimia nervosa/non-purging type, were treated with milnacipran and 20 patients completed the 8-week study. Symptom severity was evaluated using the Bulimic Investigatory Test, Edinburgh (BITE) self-rating scale before administration of milnacipran and after 1, 4, and 8 weeks treatment. The scores improved after 8 weeks, especially drive to, and regret for, binge eating. Milnacipran was more effective in patients without purging and in younger patients, while there was no difference in the efficacy of milnacipran among subtypes of eating disorders.
PMCID: PMC2515919  PMID: 18728825
milnacipran; specific serotonin and norepinephrine reuptake inhibitors; binge eating; vomiting; eating disorder; pharmacotherapy
8.  Evaluation of a Method for Fibroblast Growth Factor-23: A Novel Biomarker of Adverse Outcomes in Patients with Renal Disease 
Abstract
Background
Fibroblast growth factor 23 (FGF-23), a phosphaturic peptide hormone secreted by the osteoblasts, is an important regulator of phosphorus and vitamin D metabolism. In chronic kidney disease, FGF-23 levels rise with declining kidney function. Increasing FGF-23 levels are associated with increasing risk of mortality in dialysis patients. Two assays for FGF-23 have been reported. One assay detects only full-length/intact FGF-23. In contrast, the carboxy-terminal assay recognizes both intact and carboxy-terminal FGF-23.
Aim/Methods
The aim of this study was to evaluate both assays for FGF-23. Test samples were analyzed with both the intact and carboxy-terminal FGF-23 enzyme-linked immunosorbent assay (ELISA) kits according to manufacturers' instructions.
Results
Carboxy-terminal FGF-23 showed very good precision with coefficients of variation (CV) ranging from 4% to 10.5%, whereas the CVs for intact FGF-23 were not very good (6–37.5%). The carboxy-terminal assay was linear, stable in plasma samples, and was not affected by common interferents. Also, the carboxy-terminal FGF-23 assay appeared to correlate better with worsening of kidney function as assessed by plasma creatinine and calculated estimated glomerular filtration rate (eGFR).
Conclusion
Thus, the carboxy-terminal FGF-23 assay is robust and can be used in prospective trials to validate its utility as a biomarker of adverse outcomes in patients with renal disease.
doi:10.1089/met.2010.0030
PMCID: PMC3125567  PMID: 20707671
9.  Inhibitory Control in Bulimic-Type Eating Disorders: A Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(12):e83412.
The aim of this meta-analysis was to summarise data from neuropsychological studies on inhibitory control to general and disease-salient (i.e., food/eating, body/shape) stimuli in bulimic-type eating disorders (EDs). A systematic literature search was conducted to identify eligible experimental studies. The outcome measures studied included the performance on established inhibitory control tasks in bulimic-type EDs. Effect sizes (Hedges' g) were pooled using random-effects models. For inhibitory control to general stimuli, 24 studies were included with a total of 563 bulimic-type ED patients: 439 had bulimia nervosa (BN), 42 had anorexia nervosa of the binge/purge subtype (AN-b), and 82 had binge eating disorder (BED). With respect to inhibitory control to disease-salient stimuli, 12 studies were included, representing a total of 218 BN patients. A meta-analysis of these studies showed decreased inhibitory control to general stimuli in bulimic-type EDs (g = −0.32). Subgroup analysis revealed impairments with a large effect in the AN-b group (g = −0.91), impairments with a small effect in the BN group (g = −0.26), and a non-significant effect in the BED group (g = −0.16). Greater impairments in inhibitory control were observed in BN patients when confronted with disease-salient stimuli (food/eating: g = −0.67; body/shape: g = −0.61). In conclusion, bulimic-type EDs showed impairments in inhibitory control to general stimuli with a small effect size. There was a significantly larger impairment in inhibitory control to disease salient stimuli observed in BN patients, constituting a medium effect size.
doi:10.1371/journal.pone.0083412
PMCID: PMC3877018  PMID: 24391763
10.  Dysregulation of Brain Reward Systems in Eating Disorders: Neurochemical Information from Animal Models of Binge Eating, Bulimia Nervosa, and Anorexia Nervosa 
Neuropharmacology  2011;63(1):87-96.
Food intake is mediated, in part, through brain pathways for motivation and reinforcement. Dysregulation of these pathways may underlay some of the behaviors exhibited by patients with eating disorders. Research using animal models of eating disorders has greatly contributed to the detailed study of potential brain mechanisms that many underlie the causes or consequences of aberrant eating behaviors. This review focuses on neurochemical evidence of reward-related brain dysfunctions obtained through animal models of binge eating, bulimia nervosa, or anorexia nervosa. The findings suggest that alterations in dopamine (DA), acetylcholine (ACh) and opioid systems in reward-related brain areas occur in response to binge eating of palatable foods. Moreover, animal models of bulimia nervosa suggest that while bingeing on palatable food releases DA, purging attenuates the release of ACh that might otherwise signal satiety. Animal models of anorexia nervosa suggest that restricted access to food enhances the reinforcing effects of DA when the animal does eat. The activity-based anorexia model suggests alterations in mesolimbic DA and serotonin occur as a result of starvation coupled with excessive wheel running. These findings with animal models complement data obtained through neuroimaging and pharmacotherapy studies of clinical populations. Finally, information on the neurochemical consequences of the behaviors associated with these eating disorders will be useful in understanding these complex disorders and may inform future therapeutic approaches, as discussed here.
doi:10.1016/j.neuropharm.2011.11.010
PMCID: PMC3366171  PMID: 22138162
acetylcholine; binge eating; clinical studies; dopamine; eating disorders; opioids; rat; serotonin
11.  Increased FGF21 plasma levels in humans with sepsis and SIRS 
Endocrine Connections  2013;2(3):146-153.
Fibroblast growth factor 21 (FGF21) is a key regulator in glucose and lipid metabolism and its plasma levels have been shown to be increased not only in humans in different situations such as type 2 diabetes, obesity, and nonalcoholic fatty liver disease but also in animal models of sepsis and pancreatitis. FGF21 is considered as a pharmacological candidate in conditions associated with insulin resistance. The aim of this study was to compare FGF21 plasma levels in patients with sepsis, in patients with systemic inflammatory response syndrome (SIRS), and in healthy controls. We measured FGF21 plasma concentrations in 22 patients with established sepsis, in 11 with SIRS, and in 12 healthy volunteers. Here, we show that FGF21 levels were significantly higher in plasma obtained from patients with sepsis and SIRS in comparison with healthy controls. Also, FGF21 levels were significantly higher in patients with sepsis than in those with noninfectious SIRS. FGF21 plasma levels measured at study entry correlated positively with the APACHE II score, but not with procalcitonin levels, nor with C-reactive protein, classical markers of sepsis. Plasma concentrations of FGF21 peaked near the onset of shock and rapidly decreased with clinical improvement. Taken together, these results indicate that circulating levels of FGF21 are increased in patients presenting with sepsis and SIRS, and suggest a role for FGF21 in inflammation. Further studies are needed to explore the potential role of FGF21 in sepsis as a potential therapeutic target.
doi:10.1530/EC-13-0040
PMCID: PMC3845842  PMID: 23999826
growth factors; metabolism; inflammation
12.  Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa 
Background
Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.
Method
All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.
Results
In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.
Conclusion
The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.
doi:10.1186/1751-0759-2-5
PMCID: PMC2275291  PMID: 18267038
13.  Aberrant Brain Activation During a Response Inhibition Task in Adolescent Eating Disorder Subtypes 
Objective
Behavioral and personality characteristics associated with excessive inhibition and disinhibition are observed in patients with eating disorders, but neural correlates of inhibitory control have not been examined in adolescents with these disorders.
Methods
Thirteen adolescents with binge eating and purging, i.e., bulimia nervosa or anorexia nervosa, binge-purge subtype ,14 with anorexia nervosa, restricting subtype, and 13 healthy controls performed a rapid jittered event related Go-NoGo task. FMRI images were collected using a 3T GE scanner and a spiral pulse sequence. A whole-brain 3-group ANOVA in SPM5 was used to identify significant activation associated with the Main Effect of Group, for the comparison of correct NoGo versus Go trials. The mean activation in these clusters was extracted for further comparisons in SPSS.
Results
The binge-purge group showed significantly greater activation than the healthy control group in the bilateral precentral gyri, anterior cingulate cortex, and middle and superior temporal gyri, and greater activation compared to both controls and anorexia nervosa restricting type group in the hypothalamus and right dorsolateral prefrontal cortex. Within-group analysis found that only the anorexia nervosa, restricting group showed a positive correlation between percent correct on NoGo trials and activation in posterior visual and inferior parietal cortex regions.
Conclusions
The current study provides preliminary evidence that during adolescence, eating disorder subtypes may be distinguishable in terms of neural correlates of inhibitory control. This distinction is consistent with differences in behavioral impulsivity in these patient groups.
doi:10.1176/appi.ajp.2010.10010056
PMCID: PMC3016457  PMID: 21123315
Eating Disorders - AJP0011; Biological Markers - AJP0082; Child Psychiatry - AJP0102; Adolescents - AJP0100; Cognitive Neuroscience - AJP0069
14.  Perception of transgenerational family relationships: Comparison of eating-disordered patients and their parents 
Background
Disturbances in various elements of transgenerational family functioning patterns are not uncommon in studies of eating disorders.
We examined the relationship between patients’ perception of autonomy and intimacy in their families of origin and that of their parents in their own families of origin.
Material/Methods
The sample consisted of 112 girls who had a diagnosis of an eating disoder and their parents; 54 of the girls were diagnosed with anorexia nervosa restrictive subtype, 22 as anorexia nervosa binge/purge subtype, and 36 were diagnosed with bulimia nervosa. We had 2 control groups: 1 group consisted of 36 girls diagnosed with a depressive episode, dysthymia, or adjustment disorder with depressed mood and the other group was 85 female students from schools in Cracow, Poland and their parents. We used the the Family of Origin Scale to assess perception of family relationships. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS 20.0.PL; Chicago, IL, USA).
Results
There was a significant association between daughters’ and fathers’ perceptions of autonomy in their families of origin in all groups. There was no significant association between daughters’ and mothers’ perceptions in all groups. The strongest correlation was between the non-clinical sample of girls and their fathers and for the bulimic group.
Conclusions
We did not detect any link indicating the specificity of transgenerational transmission of autonomy and intimacy in eating disorders. The results point to the importance of the father figure in studies of family systems, including the context of family transmission.
doi:10.12659/MSM.889432
PMCID: PMC3867474  PMID: 24309425
anorexia nervosa; bulimia nervosa; family; autonomy; intimacy
15.  Disordered eating among mothers of Polish patients with eating disorders 
Summary
Background
The aim of this study was to assess attitudes towards eating as measured by the Eating Attitude Test (EAT26) among mothers of girls diagnosed with various types of eating disorders, in comparison with mothers of depressive girls and their relationship with daughters’ results 14 years after the beginning of the Polish political and cultural transformation of 1989.
Material/Methods
The data of 68 mothers and their daughters were used in statistical analysis (anorexia nervosa restrictive type: 18, anorexia nervosa binge/purge type: 12, bulimia: 14, depression: 24). The mean age in the group of mothers was 43.5 (SD 5.3), daughters: 16.7 (SD 1.4).
Results
In the group of mothers, the results of EAT26 test were lower than results of the general population of Polish females or patients’ mothers obtained in a different cultural context. Results from girls with an eating disorder diagnosis considerably exceed the mean result of Polish population studies of teenagers. There were no statistically significant differences between the EAT26 results of mothers of girls with various types of eating disorders and mothers of depressive girls. Sociocultural variables such as education and place of residence of mothers also did not differentiate the studied groups and did not have a significant influence on attitudes towards weight and body shape presented by the studied mothers.
Conclusions
The obtained results may suggest that in the studied population, the social background of mothers and disturbances of their own mothers’ attitudes towards weight and body shape were not an important and specific risk factor in the development of their daughters’ eating disorders.
doi:10.12659/MSM.883605
PMCID: PMC3560793  PMID: 23197240
anorexia nervosa; bulimia nervosa; culture; Westernization; eating disorders
16.  Substance Use Disorders in Women with Anorexia Nervosa 
Objective
We examined prevalence of substance use disorders (SUD) in women with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating.
Method
Participants (N = 731) were drawn from the International Price Foundation Genetic Studies.
Results
The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. Individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status.
Conclusion
SUD are common in AN and are associated with bulimic symptomatology. Results underscore the heterogeneity in AN, highlighting the importance of screening for SUD across AN subtypes.
doi:10.1002/eat.20670
PMCID: PMC2807480  PMID: 19260043
eating disorders; anorexia nervosa; bulimia nervosa; drug use; alcohol related disorders; cannabis
17.  Validity and Utility of Subtyping Anorexia Nervosa 
Objective
The purpose of this paper is to review the available literature that addresses the predictive validity and utility of subtyping anorexia nervosa patients into binge/purge and restrictor subtypes.
Method
Literature was reviewed including studies that compared individuals with subtype diagnoses on clinical and outcome variables as well as more recent research examining the frequency of diagnostic crossover.
Results
Several studies found that in general the binge/purge subtype patients have more psychopathology, tend to be older and tend to have a worse outcome. More recent studies which have examined diagnostic crossover suggest that the rate of crossover from the restrictor subtype to the binge/purge subtype is substantial. Crossover from the binge/purge to the restrictor subtype appears to occur less commonly. There is also literature documenting crossover from anorexia nervosa to bulimia nervosa and a small literature looking at crossover from bulimia nervosa to anorexia nervosa.
Discussion
The results of this review suggest that although there is generally progression from restrictor anorexia nervosa to binge/purge anorexia nervosa to bulimia nervosa in a sizeable number of patients, other crossover patterns can be seen as well, and the amount of crossover is quite large. This suggests a lack of predictive validity for subtypes. Validity and Utility of Subtyping Anorexia Nervosa
doi:10.1002/eat.20717
PMCID: PMC2844095  PMID: 19598270
18.  Eating disorder subtypes differ in their rates of psychosocial improvement over treatment 
Background
Individuals with Anorexia Nervosa (AN) are renowned for their poor short- and long-term treatment outcomes. To gain more insight into the reasons for these poor outcomes, the present study compared patients with AN-R (restrictive subtype), AN-BP (binge-purge subtype), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) over 12 weeks of specialized eating disorders treatment.
Eighty-nine patients completed the Eating Disorder Examination- Questionnaire (EDE-Q) and various measures of psychosocial functioning at baseline, and again after weeks 3, 6, 9, and 12 of treatment.
Results
Multilevel modeling revealed that, over the 12 weeks, patients with AN-BP and AN-R had slower improvements in global eating disorder pathology, shape concerns, and self-compassion than those with EDNOS and BN. Patients with AN-BP had slower improvements in shame, social safeness (i.e., feelings of warmth in one’s relationships), and received social support compared to those with AN-R, BN, and EDNOS.
Conclusions
These findings support the need for more effective and comprehensive clinical interventions for patients with AN and especially AN-BP. Results also highlight not-yet studied processes that might contribute to the poor outcomes AN patients often face during and after treatment.
doi:10.1186/2050-2974-2-2
PMCID: PMC4081788  PMID: 24999425
Anorexia nervosa; Transdiagnostic; Treatment process; Treatment outcome; Change trajectories; Self-compassion; Received social support; Shame; Social safeness
19.  Is decision making really impaired in eating disorders? 
Neuropsychology  2010;24(6):808-812.
Objective
Decision-making has been reported to be reduced in eating disorders. However, studies are sparse and have been carried out in various selected populations. The current study was arranged to confirm previous observations and to assess the relationship between decision-making and dimensions relevant to eating disorders.
Method
Patients suffering from anorexia nervosa (n=49), bulimia nervosa (n=38), and healthy controls (n=83) were assessed using the Iowa Gambling Task (IGT). All patients were euthymic and free of psychotropic medication. Self-questionnaires (EDI-2 and EAT) were used to assess clinical dimensions relevant to eating disorders.
Results
No significant differences in IGT performance were observed between patients and healthy controls, or between restrictive and purging types of anorexia nervosa. No correlations were found between IGT performance and eating disorder questionnaires.
Conclusion
These results do not support reduced decision-making in patients with eating disorders, and suggest that previously reported alterations could be related to other clinical characteristics. This should stimulate new topic-related studies designed to reach a firm conclusion.
doi:10.1037/a0019806
PMCID: PMC3074243  PMID: 20853958
Anorexia Nervosa; complications; psychology; Bulimia Nervosa; complications; psychology; Cognition Disorders; diagnosis; etiology; Decision Making; physiology; Female; Humans; Neuropsychological Tests; Questionnaires; anorexia nervosa; bulimia nervosa; Iowa Gambling Task; neuropsychology
20.  Patterns of remission, continuation, and incidence of broadly defined eating disorders during early pregnancy in the Norwegian Mother and Child Cohort Study (MoBa) 
Psychological medicine  2007;37(8):1109-1118.
Background:
We explored the course of broadly defined eating disorders during pregnancy in the Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of Public Health.
Method:
41,157 pregnant women, enrolled at approximately 18 weeks gestation, had valid data from the Norwegian Medical Birth Registry. We collected questionnaire based diagnostic information on broadly defined anorexia nervosa, and bulimia nervosa (BN), and eating disorders not otherwise specified (EDNOS). EDNOS subtypes included binge eating disorder (BED) and recurrent self-induced purging in the absence of binge eating (EDNOS-P). We explored rates of remission, continuation, and incidence of BN, BED and EDNOS-P during pregnancy.
Results:
Pre-pregnancy prevalence estimates were 0.1% for anorexia nervosa, 0.7% for BN, 3.5% for BED, and 0.1% for EDNOS-P. During early pregnancy, estimates were 0.2% (BN), 4.8% (BED), and 0.1% (EDNOS-P). Proportions of individuals remitting during pregnancy were 78% (EDNOS-P), 40% (BN purging), 39% (BED), 34% (BN any type), 29% (BN non-purging type). Additional individuals with BN achieved partial remission. Incident BN and EDNOS-P during pregnancy were rare. For BED, the incidence rate was 1.1 per 1000 person-weeks equating to 711 new cases of BED during pregnancy. Incident BED was associated with indices of lower socioeconomic status.
Conclusions:
Pregnancy appears to be a catalyst for remission of some eating disorders, but also a vulnerability window for the new onset of broadly defined BED especially in economically disadvantaged individuals. Vigilance by health care professionals for continuation and emergence of eating disorders in pregnancy is warranted.
doi:10.1017/S0033291707000724
PMCID: PMC2657803  PMID: 17493296
21.  Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa 
Background
The present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC) and high-protein (HP) breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls.
Methods
We examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7), BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9) and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8). Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits.
Results
Fasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups.
Conclusions
Significant increase of obestatin and NPY in AN and BN patients may indicate their important role as the markers of eating disorders. Different reactions of ghrelin and PYY to breakfast consumption among groups suggest that role of these hormones in regulation of energy homeostasis can be adjusted in dependence to acute status of eating disorder.
doi:10.1186/1743-7075-9-52
PMCID: PMC3533897  PMID: 22681985
Ghrelin; Obestatin; NPY; PYY; Anorexia nervosa; Bulimia nervosa; High-carbohydrate breakfast; High-protein breakfast
22.  FGF-23 and PTH levels in patients with acute kidney injury: A cross-sectional case series study 
Background
Fibroblast growth factor-23 (FGF-23), a novel regulator of mineral metabolism, is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. However, whether FGF-23 has an analogous role in acute kidney injury is unknown. The goal of this study was to measure FGF-23 levels in critically ill patients with acute kidney injury to determine whether FGF-23 levels were elevated, as in chronic kidney disease.
Methods
Plasma FGF-23 and intact parathyroid hormone (PTH) levels were measured in 12 patients with acute kidney injury and 8 control subjects.
Results
FGF-23 levels were significantly higher in acute kidney injury cases than in critically ill subjects without acute kidney injury, with a median FGF-23 level of 1948 RU/mL (interquartile range (IQR), 437-4369) in cases compared with 252 RU/mL (IQR, 65-533) in controls (p = 0.01). No correlations were observed between FGF-23 and severity of acute kidney injury (defined by the Acute Kidney Injury Network criteria); among patients with acute kidney injury, FGF-23 levels were higher in nonsurvivors than survivors (median levels of 4446 RU/mL (IQR, 3455-5443) versus 544 RU/mL (IQR, 390-1948; p = 0.02). Severe hyperparathyroidism (defined as intact PTH >250 mg/dL) was present in 3 of 12 (25%) of the acute kidney injury subjects versus none of the subjects without acute kidney injury, although this result did not meet statistical significance.
Conclusions
We provide novel data that demonstrate that FGF-23 levels are elevated in acute kidney injury, suggesting that FGF-23 dysregulation occurs in acute kidney injury as well as chronic kidney disease. Further studies are needed to define the short- and long-term clinical effects of dysregulated mineral metabolism in acute kidney injury patients.
doi:10.1186/2110-5820-1-21
PMCID: PMC3224491  PMID: 21906363
23.  Serum Concentrations of Fibroblast Growth Factors 19 and 21 in Women with Gestational Diabetes Mellitus: Association with Insulin Resistance, Adiponectin, and Polycystic Ovary Syndrome History 
PLoS ONE  2013;8(11):e81190.
Background
Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters.
Method
Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters.
Results
Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history.
Conclusions
Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.
doi:10.1371/journal.pone.0081190
PMCID: PMC3834317  PMID: 24260557
24.  Serum Amylase in Bulimia Nervosa and Purging Disorder: Differentiating the Association with Binge Eating versus Purging Behavior 
Physiology & behavior  2011;104(5):684-686.
Objective
Elevated serum amylase levels in bulimia nervosa (BN), associated with increased salivary gland size and self-induced vomiting in some patients, provide a possible marker of symptom severity. The goal of this study was to assess whether serum hyperamylasemia in BN is more closely associated with binge eating episodes involving consumption of large amounts of food or with purging behavior.
Method
Participants included women with BN (n=26); women with “purging disorder” (PD), a subtype of EDNOS characterized by recurrent purging in the absence of objectively large binge eating episodes (n=14); and healthy non-eating disorder female controls (n=32). There were no significant differences in age or body mass index (BMI) across groups. The clinical groups reported similar frequency of self-induced vomiting behavior and were free of psychotropic medications. Serum samples were obtained after overnight fast and were assayed for alpha-amylase by enzymatic method.
Results
Serum amylase levels were significantly elevated in BN (60.7 ± 25.4 international units [IU]/liter, mean ± sd) in comparison to PD (44.7 ± 17.1 IU/L, p < 02) and to Controls (49.3 ± 15.8, p < .05).
Conclusion
These findings provide evidence to suggest that it is recurrent binge eating involving large amounts of food, rather than self-induced vomiting, which contributes to elevated serum amylase values in BN.
doi:10.1016/j.physbeh.2011.06.025
PMCID: PMC3204380  PMID: 21781981
bulimia nervosa; purging disorder; self-induced vomiting; binge eating; serum amylase; hyperamylasemia
25.  Patterns of Comorbidity of Eating Disorders and Substance Use in Swedish Females 
Psychological medicine  2009;40(1):105-115.
Background
Little is known about the association of eating disorder (ED) subtypes across multiple categories of substance use (SU) in population-based samples. We examined the association between EDs and SU in a large population-based sample.
Method
Female participants (N=13,297) were from the Swedish Twin Registry (Lichtenstein et al., 2006). SU was examined in four defined groups − (1) anorexia nervosa (AN); (2) bulimia nervosa (BN); (3) anorexia nervosa and bulimia nervosa (ANBN); and (4) binge eating disorder (BED) as well as a referent group without EDs (no ED). Secondary analyses examined differences between restricting AN (RAN) and binge and/or purge AN (ANBP).
Results
In general, EDs were associated with greater SU relative to the referent. The AN group had significantly increased odds for all illicit drugs. Significant differences emerged across the RAN and ANBP groups for alcohol abuse/dependence, diet pills, stimulants, and polysubstance use with greater use in the ANBP group. Across ED groups, (1) the BN and ANBN groups were more likely to report alcohol abuse/dependence relative to the AN group, (2) the ANBN group was more likely to report diet pill use relative to the AN, BN, and BED groups, and (3) the BN group was more likely to report diet pill use relative to the no ED, AN and BED groups.
Conclusions
EDs are associated with a range of SU behaviors. Improved understanding of how they mutually influence risk could enhance understanding of etiology and prevention.
doi:10.1017/S0033291709005662
PMCID: PMC2788663  PMID: 19379530

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