Nobuatsu Nagai

Fasting plasma ghrelin levels in subtypes of anorexia nervosa.

Ghrelin has a role in regulating eating behavior and energy metabolism in the central nervous system, and has been reported to play an important role in the pathophysiology of anorexia nervosa (AN). The aim of the present study was to compare fasting plasma ghrelin levels in different subtypes of untreated AN patients. The subjects included 39 female AN patients and 11 female controls. The patients were then divided into two subtypes as follows: 19 AN patients with restricting (AN-R) and 20 AN patients with binge-eating/purging (AN-BP) form of the illness. Blood samples from subjects after an overnight fast were used to analyze plasma ghrelin concentrations. Plasma ghrelin concentrations in both AN-R and AN-BP were negatively correlated with body mass index (BMI). The mean plasma ghrelin levels in both AN-R and AN-BP were significantly higher than that in controls. The mean ghrelin level in AN-BP was significantly higher than that in AN-R. However, mean BMI and serum potassium in both groups were not significantly different. These results suggest that both BMI and the presence of binge-eating/purging may have some influence on fasting plasma ghrelin levels in patients with AN.

Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders

Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 non-purging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders.

Altered ghrelin and peptide YY responses to meals in bulimia nervosa

Objective  In recent years great advances have been made in our understanding of the peripheral signals produced within the gastrointestinal tract that regulate appetite, such as ghrelin and peptide YY (PYY). While ghrelin elicites hunger signals, PYY elicites satiety. Therefore, alterations in hormone physiology may play a role in the pathogenesis of bulimia nervosa (BN). In this study, we investigated the postprandial profile of ghrelin and PYY levels in patients with BN.

Comparison of regional cerebral blood flow in patients with eating disorders

We used single photon emission computed tomography (SPECT) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow (rCBF) in five patients with bulimia nervosa (BN), eight patients with anorexia nervosa (AN), and in nine healthy controls. The SPECT examinations were performed before and after food intake stimulus, and the values of the corrected ratio (R) for rCBF in 10 cerebral cortical regions before (Rbefore) and after eating (Rafter) were calculated. The asymmetry indices (AI) of the R values for the left and right side of each cortical region and the percent change from Rbefore to Rafter (%change) were computed. In comparison with the other two groups, BN patients showed significantly higher Rbefore values in the bilateral inferior frontal and left temporal regions. The AN patients showed significantly lower Rbefore values in the left parietal region than the control group. There were no significant differences in Rafter values among the three groups. The %change values in the AN group showed the greatest increase in 9 out of the 10 regions. In contrast to the positive values obtained from the 10 regions observed in the AN group, 5 out of the 10 regions in the BN group showed negative values. Among the three groups, significant differences in %change were observed on both sides of the inferior frontal, temporal, parietal, and occipital regions. These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging.

Decreases in blood perfusion of the anterior cingulate gyri in Anorexia Nervosa Restricters assessed by SPECT image analysis.

BackgroundIt is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics.MethodsThe subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated.ResultsSPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups.ConclusionsThese findings suggest that some localized functions ofthe ACCare possibly relevant to the psychopathological aspects of AN-R.

Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa.

Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa (AN) as a consequence of prolonged starvation. The current study examines the effect of nutritional rehabilitation with improvement of eating behavior on ghrelin and GH levels in AN patients during the course of inpatient treatment. The subjects included 34 female AN patients and 9 age-matched female controls. Fasting blood samples were collected before, during and after treatment. For data analysis, AN subjects were divided into three subtypes. The first group included seven patients with emergent hospitalization (E-AN), who were accompanied by severe emaciation due to their inability for food intake for more than a month. The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge-eating/purging (AN-BP) patients. There were significant correlations between ghrelin, GH and body mass index (BMI) before treatment in all subjects. However, ghrelin levels were not significantly correlated with BMI and GH although there was a relationship between GH and BMI after treatment. Before treatment, E-AN patients had the highest levels of ghrelin and GH with the lowest glucose levels and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN-R group. During treatment, comparing with the controls group only the AN-R group showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group, who showed improved glucose levels, and the AN-BP group, who stopped vomiting behavior due to our treatment, decreased ghrelin levels. After treatment, only the AN-BP group showed a higher ghrelin level as compared to the controls. Although GH levels of the three AN groups decreased gradually according to our treatment progress, it still showed the higher value than the control group at the end of the treatment because every AN patients could not reach to more than 80% of their ideal body weight at discharge. These findings suggest that (1) severe emaciation with abnormal fasting hypoglycemia in AN patients may cause very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate to nutritional status and (3) that ghrelin may be influenced by not only nutritional status but also the eating behavior of the patients.

Clinical features of patients with anorexia nervosa: Assessment of factors influencing the duration of in-patient treatment

We investigated that factors affecting the duration of in-patient treatment of patients with anorexia nervosa by comparing pretreatment clinical features with the length of hospitalization in 55 patients. Only patients who had completed the entire course of treatment were included in our analysis. Longer hospitalization was correlated with: poor social adaptation; anxiety and/or personality disorders before onset; older age at onset; older age at admission to our hospital; lower minimum body weight after onset; lower body weight at admission; longer duration of illness; frequent previous hospital treatment and/or history of in-patient treatment for anorexia nervosa or other somatic disorders after onset; habitual stimulant (alcohol, coffee and/or cigarettes) abuse; and a history of stealing after onset. Step-wise regression analysis revealed that minimum body weight after onset and age at admission explained 47% of the variance in the duration of in-patient treatment. We also describe the nature of in patient treatment typically offered to patients with anorexia nervosa in Japan.

Changes in taste responsiveness in patients with anorexia nervosa during behavior therapy

We evaluated the changes in taste responsiveness of anorexia nervosa (AN) patients during behavior therapy. Taste responsiveness of AN patients was lower at admission when compared to controls but it improved significantly over the course of treatment (p < 0.01). Taste responsiveness improved prior to increase in body weight. No significant correlation was noted between weight gain and improvement in taste responsiveness. The period required to reach a food intake of 1600 Kcal/day and the duration of hospitalization were highly correlated (r = 0.72, p < 0.05). Those who reached 1600 Kcal/day earlier showed more rapid improvements in taste responsiveness. These results suggest that decreased taste responsiveness in AN patients can rapidly improve and such early improvement may result in better progression of treatment.

Glucose tolerance predicts short-term refeeding outcome in females with anorexia nervosa.

Objective: Little is known about biologic predictors of refeeding outcome in anorexia nervosa (AN). Because nutritional status mirrors glucose metabolism during an oral glucose tolerance test (OGTT) in AN, this study investigated whether pretreatment glucose response patterns during the OGTT might be associated with refeeding progress in patients with AN. Methods: Sixty-four female patients with anorexia (33 restrictors and 31 binge/purgers) and 13 healthy control subjects underwent an OGTT before nutritional rehabilitation, including desensitization to fear of energy intake of 1000 to 1600 kcal/day. Patients were divided into flat-type responders, impaired glucose tolerance (IGT)-type responders, and normal-type glucose responders. Daily energy intake, weekly weight gain, and the duration of desensitization period were evaluated until the 12th week. Results: The patients with anorexia consisted of 20 flat-type, 21 IGT-type, and 23 normal- type responders. Normal-type responders required a shorter time to complete the desensitization period than other responders (p = .003 for restrictors, p < .001 for binge/purgers). In terms of refeeding progress, significant group effects for daily energy intake and weekly weight gain were evident in restrictors (p = .006, p = .028, respectively) and binge/purgers (p < .001, p = .003, respectively); normal-type responders showed good refeeding progress compared with other responders in both AN subtypes. Conclusions: The present study found a close relationship between pretreatment glucose responses, therapeutic progress of desensitization to fear of energy intake, and refeeding progress in both AN subtypes. Our findings suggest that glucose tolerance may be a useful predictor of short-term refeeding outcome in this disorder. AN = anorexia nervosa; ANOVA = analysis of variance; AUC = insulin area under the curve; BMI = body mass index; DM = diabetes mellitus; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; FBG = fasting blood glucose concentration; FIRI = fasting serum insulin concentration; HOMA-IR = homeostasis model assessment for insulin resistance; IGT = impaired glucose tolerance; II15min = insulinogenic index at 15 minutes; OGTT = oral glucose tolerance test.

A significant nationwide increase in the prevalence of eating disorders in Japan: 1998-year survey

Abstract Objective: To investigate the prevalence and the clinico-epidemiological features of eating disorders (ED) in Japan. Methods: In January 1998, a self-reported questionnaire, asking about the number of ED was mailed to 23,401 institutions and a second questionnaire asking about the clinoco-epidemiological features of ED was mailed to 1404 institutions, the institutions being located throughout Japan. We calculated the 1-year prevalence rates of ED from these data. Results: The prevalence rates of anorexia nervosa in this survey showed 10.0 cases per 100,000 of general population, which were four times higher than those in 1993. The rates for bulimia nervosa indicated 5.2 cases per 100,000, which were 4.7 times higher than in 1993. With respect to clinico-epidemiological features, short-term cases (duration of illness 9 years). Moreover, fewer than half of ED patients indicated “improved” in clinical course, “sufficient” in family support and “adjusted” in social adaptation. Conclusions: These findings suggest the expansion of age groups with ED, vulnerable family structure, and insufficient social support systems in contemporary Japan, and also suggested that the prevalence rates in Japan would soon reach those in the west.