Daisuke Yasuhara

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.

Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa.

BACKGROUND Obestatin is a recently identified ghrelin gene product that was reported to inhibit appetite and gastric motility in contrast to ghrelin. We investigated fasting obestatin and ghrelin levels in patients with obesity and anorexia nervosa. METHODS Fasting plasma obestatin, acyl-ghrelin, desacyl-ghrelin, leptin, glucose serum adiponectin, and insulin were measured in 10 obese subjects, 11 restricting-type anorexics, and 11 control subjects. RESULTS Obese group had significantly lower levels of obestatin (p < .01), while anorexic group had significantly higher levels (p < .01). Obestatin was negatively correlated with body mass index (BMI) (r = -.74), glucose (r = -.56), insulin (r = -.55), leptin (r = -.66), and also with the homeostasis model assessment of insulin resistance (HOMA-R) (r = -.49) and was positively correlated with acyl-ghrelin (r = .65) and desacyl-ghrelin (r = .60). No correlation was seen between obestatin and adiponectin, but the latter was negatively correlated with both acyl-ghrelin and desacyl-ghrelin. Desacyl-ghrelin to acyl-ghrelin ratio was significantly different between anorexic and control groups (p < .05), while no difference was seen between obese and control groups. CONCLUSIONS Both obestatin and ghrelin are increased in anorexic and decreased in obesity. We suggest that obestatin is a nutritional marker reflecting body adiposity and insulin resistance.

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.

Obestatin, Acyl Ghrelin, and Des-acyl Ghrelin Responses to an Oral Glucose Tolerance Test in the Restricting Type of Anorexia Nervosa

BACKGROUND Obestatin is a recently identified peptide encoded by the same ghrelin gene. It has been reported that obestatin has anorexigenic and antigastroprokinetic activities as opposed to ghrelin. We investigated simultaneously obestatin, acyl ghrelin, and des-acyl ghrelin in the restricting type of anorexia nervosa (AN-R) patients. METHODS Three hormonal responses to the oral glucose tolerance test (OGTT) were measured in 10 AN-R patients and 10 healthy women. RESULTS Plasma obestatin, acyl ghrelin, and des-acyl ghrelin levels were significantly higher in AN-R patients than in control subjects throughout the OGTT. All of the three hormones decreased after the OGTT in both groups. CONCLUSIONS We found that AN-R patients exhibited increased plasma levels of obestatin, acyl ghrelin, and des-acyl ghrelin throughout the OGTT compared with control subjects. The hormonal differences between groups are statistically most significant in obestatin, suggesting obestatin may serve as a marker reflecting both acute and chronic changes of the nutritional state in AN-R patients.

Plasma nesfatin-1 concentrations in restricting-type anorexia nervosa

Restricting-type anorexia nervosa (AN-R) is characterized by chronic food restriction and severe emaciation due to various cognitive biases such as a distorted self-image. In spite of several treatments, AN-R continues to be a refractory disease because of its unknown pathogenesis. Although previous studies have shown that changes in feeding regulatory peptides such as ghrelin are involved in anorexia, few reports have described the relationship between AN-R and nesfatin-1, a recently identified satiety peptide. Therefore, we examined the plasma nesfatin-1 levels in AN-R patients to determine its role in AN-R. A total of 15 women participated in the study; 7 patients with AN-R and 8 age-matched healthy controls (average BMI, 13.02 ± 0.30 vs. 21.57 ± 0.48, respectively). Our results showed that plasma nesfatin-1 levels were significantly lower in AN-R group than in control group (6.23 ± 0.70 ng/ml vs. 8.91 ± 0.85 ng/ml, respectively, P<0.05). Plasma acyl ghrelin and des-acyl ghrelin levels were significantly higher in AN-R group than in control group (acyl ghrelin: 62.4 ± 10.15 fmol/ml vs. 27.20 ± 5.60 fmol/ml, P<0.01 and des-acyl ghrelin: 300.17 ± 55.95 fmol/ml vs. 107.34 ± 40.63 fmol/ml, P<0.05). Although AN-R is associated with emaciation for a prolonged period, our result suggested that nesfatin-1 levels may be regulated by nutrition status and response to starvation.

Eating pattern and the effect of oral glucose on ghrelin and insulin secretion in patients with anorexia nervosa

objective  Ghrelin is thought to be involved in the regulation of eating behaviour and energy metabolism in acute and chronic feeding states. Circulating plasma ghrelin levels in healthy humans have been found to decrease significantly after oral glucose administration. Because it is suggested that eating behaviour may influence the secretion of ghrelin and insulin in anorexia nervosa (AN), we examined the effect of oral glucose on ghrelin and insulin secretion in subtypes of AN patients.

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.

Ghrelin concentrations and cardiac vagal tone are decreased after pharmacologic and cognitive-behavioral treatment in patients with bulimia nervosa.

Patients with bulimia nervosa (BN) have bulimic and depressive symptoms, which have been associated with abnormalities in the neuroendocrine and vagal systems. Subjects included twenty-four female drug-free outpatients with BN that were selected from patients seeking treatment for eating behavior in our hospital along with twenty-five age-matched healthy females who served as controls. We investigated ghrelin and leptin levels, cardiac vagal tone and sympathovagal balance, frequency of sets of binge-eating and vomiting episodes per week and the Profile of Mood States (POMS) depression scale in BN before and after a 16-week administration of the serotonin selective reuptake inhibitor (SSRI) paroxetine combined with cognitive-behavioral therapy. Compared to controls, the BN group had higher ghrelin levels and resting cardiac vagal tone, and lower leptin levels and resting cardiac sympathovagal balance before treatment, although there was a significant difference between the two groups for the body mass index (BMI). The elevated ghrelin levels (301.7 +/- 18.9 pmol/l, mean +/- SEM vs. 202.8 +/- 15.6 pmol/l, P < 0.01), cardiac vagal tone (2246.4 +/- 335.5 ms(2) vs. 1128.5 +/- 193.3 ms(2), P < 0.01), frequency of sets of binge-eating and purging episodes and T scores for the POMS depression scale were all significantly decreased after treatment despite similar BMI, percent body fat and leptin levels. In close association with cardiac vagal function and ghrelin recoveries, abnormal eating behavior and depressive symptoms improved, indicating the usefulness of these indexes in the assessment of clinical condition and therapeutic efficacy in BN.

Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain

OBJECTIVE Restricting-type anorexia nervosa (AN-R), characterized by severe emaciation with long-term food restriction, is often difficult to treat. The present study investigated the overall intelligence quotient (IQ) scores and cognitive functions of patients with AN-R. METHODS Fourteen female inpatients with AN-R (body mass index 12.84 ± 0.41 kg/m²) and 10 healthy female participants participated in this study from 2007 through 2010. The Wechsler Adult Intelligence Scale, Third Edition and the Eating Disorder Inventory-II were administered. This research was performed at Kagoshima University Hospital. RESULTS In the AN-R group, overall IQ scores showed borderline intelligence (e.g., full-scale IQ 75.86 ± 1.79, P < 0.01); the scores were significantly lower than those in the comparison group. There were negative correlations between lower IQs and higher Eating Disorder Inventory-II scores. After the weight restoration, the IQ scores of subjects with AN-R with regard to the visuospatial scales were significantly higher than before (P < 0.01); however, the auditory cognitive scores were unchanged. CONCLUSION These lower IQ scores could be connected to the psychological and behavioral traits in patients with AN-R. These problems should be considered by medical staff members who seek to treat patients with AN-R successfully.

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.