Incomplete restoration of the secretion of ghrelin and PYY compared to insulin after food ingestion following weight gain in anorexia nervosa.

BACKGROUND: In humans, ghrelin has been found to stimulate appetite while PYY3-36 to reduce it; these orexigenic and anorexigenic peptides play significant roles in appetite control. We investigated pre- and postprandial responses of ghrelin and PYY in anorexia nervosa (AN) and the influence of weight gain. METHODS: Plasma ghrelin, PYY3-36, glucose and insulin responses after ingestion of a 400 kcal standard meal were measured in 14 patients with restricting type of AN and 12 controls. The AN patients were evaluated before therapy and after inpatient therapy. Psychometry was performed by the use of Eating Disorders Inventory. RESULTS: Ghrelin was suppressed during the meal test, while PYY3-36 was increased in all of the groups. Before therapy, AN patients had significantly increased levels of ghrelin and PYY3-36 compared to the control (P<0.01). After therapeutic intervention, as the nutritional status of AN patients improved, the secretion of these hormones were increased (P<0.05), but not normalized as in psychological testing. In contrast, insulin and glucose responses were normalized after inpatient therapy. CONCLUSIONS: We found that both ghrelin and PYY3-36 increased in AN patients and these changes were not normalized in contrast to insulin after treatment. The increase in both orexigenic ghrelin and anorexigenic PYY3-36 may have a role in pathological eating behavior in AN.

The effects of bone therapy on tibial bone loss in young women with anorexia nervosa.

OBJECTIVE: Osteoporosis is recognized as a common medical complication of anorexia nervosa (AN). The purpose of the current study was to investigate the recovery mechanism of osteoporosis in AN and the effect of medical treatment on the skeletal system. METHOD: We conducted a randomized placebo-controlled study of the effects of etidronate and calcium and vitamin D on bone loss in 41 outpatients with the restricting type of AN (AN-R). We measured the tibial speed of sound (SOS) before and after 3 months of treatment. RESULTS: The bone mineral density (BMD) of the tibial SOS change in both the etidronate group and the calcium and vitamin D Group was significantly greater (p < .001) than in the control group. Urine-N-telopeptide cross-links of type I collagen (NTx) before and after treatment decreased significantly (p < .01) in the etidronate group. CONCLUSION: These findings suggest that both etidronate and calcium and vitamin D are equally efficacious for reversing the degree of osteoporosis in patients with AN.

Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain.

We investigated changes in regional cerebral blood flow (rCBF) before and after weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison with findings in normal subjects. We assessed resting rCBF using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 12 AN-R patients and 11 controls. Each patient was examined at two time points, at the beginning of treatment and after weight gain (average examination interval=88+/-26 days). Control subjects were examined only once. Before treatment, the AN-R group had lower rCBF in the bilateral anterior lobes, including the anterior cingulate cortex (ACC), and in the right parietal lobe, the insula, and the occipital lobes. After weight gain, the patients showed significant increases in the right parietal lobe and decreases in the basal ganglia and cerebellum in accordance with significant improvement in body weight and eating attitudes. However, they showed persistent decreases in the ACC area even after weight gain compared with findings in the controls. A significant positive correlation was observed between body mass index and rCBF in the occipital lobes in the patients. These results suggest that weight gain is associated with a normalization of rCBF in a number of brain areas, but that the low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.

"End-stage kidney" in longstanding bulimia nervosa.

OBJECTIVE: The extent of renal damage over long-term binge/purges has not been well documented in bulimia nervosa (BN). METHOD: We describe a 52-year-old woman with longstanding BN subsequent to an 8-year history of anorexia nervosa (AN). RESULTS: The patient showed chaotic binge/purges and chronic severe hypokalemia after recovery from AN at age 26 years, and renal biopsy showed juxtaglomerular hyperplasia, which was diagnosed as pseudo-Bartter's syndrome. DISCUSSION: Over the following 26 years, the patient's eating behaviors remained chaotic, and her renal function gradually deteriorated. After the patient died of pneumonia and sepsis at age 52 years, autopsy of her kidney showed chronic interstitial nephritis, proximal tubular swelling, and diffuse glomerular sclerosis, suggesting chronic glomerular injury associated with long-term binge/purges. To our knowledge, this is the first case report of a patient with BN with long-term binge/purges who developed an eventual "end-stage kidney" characterized by hypokalemic nephropathy and diffuse glomerulosclerosis.

Psychologic management of brace therapy for patients with idiopathic scoliosis.

STUDY DESIGN: A trial of brace therapy modified by a measured personality pattern of patients with idiopathic scoliosis was performed. OBJECTIVE: To evaluate the effectiveness of performing personality tests for patients with idiopathic scoliosis who undergo brace therapy. SUMMARY OF BACKGROUND DATA: Brace therapy has often been used for the treatment of scoliosis. However, emotional distress can result from this therapy. Few attempts have been made to reduce such stress. METHODS: A test using the Maudsley Personality Inventory was performed on 145 adolescent females with idiopathic scoliosis, treated with brace therapy alone, before the start of brace therapy and 1 month after the start of brace therapy. On the basis of test results, the patients were rated as normal type and four abnormal types. Brace therapy was continued considering the personality pattern of patients. For all patients, changes in psychologic test results, compliance with braces wearing instructions, and correction of scoliosis were analyzed. RESULT: Of the 134 patients rated as normal before the start of therapy, 108 patients were rated as abnormal pattern when tested 1 month after the start of therapy. After performing autogenic training for patients with E-N+ and E-N- personalities, and giving advice to school teachers to decrease the emotional stress for patients with E+N+ personality, 47 patients were finally rated as abnormal pattern. In total, 12 (8%) of the 145 patients dropped out. In dropouts, the average pretreatment deformity of 29 degrees (range: 21 degrees -37 degrees ) had increased to an average of 37 degrees (range, 31 degrees -48 degrees ). CONCLUSION: Psychologic tests may be useful and provide a means of modifying brace therapy tailored to the psychologic conditions of individual patients.

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.

Insulinogenic index at 15 min as a marker of stable eating behavior in bulimia nervosa.

BACKGROUND & AIMS: The aim of this study was to determine the relationship between insulinogenic index at 15 min (II15 min), body weight maintenance, and the presence of vomiting in patients with bulimia nervosa. METHODS: Forty-eight bulimic inpatients and 14 controls underwent an oral glucose tolerance test on the seventh hospital day. We calculated II15 min and other biological markers, including serum amylase concentrations. During the first week after admission, we monitored the frequency of vomiting and calculated changes in body weight. Patients were divided into 4 subgroups according to the presence of vomiting and weight loss. RESULTS: Two-factor analysis of variance of the II15 min value revealed significant main effects of vomiting and body weight change (P < 0.001 for both). The II15 min values for controls and bulimic patients with weight loss and no vomiting were lower than those of other bulimic groups. The II15 min values were positively correlated with serum amylase concentrations (r = 0.37, P < 0.01), body weight change (r = 0.35, P < 0.05), and frequencies of vomiting (r = 0.49, P < 0.05). CONCLUSIONS: These findings suggest that II15 min values may be a useful marker for assessing the stability of eating behavior in patients with bulimia nervosa.

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. DESIGN AND PATIENTS: Twenty female AN patients and 10 age-matched female controls were subjects. The patients were subdivided into two subtypes based on eating behaviour as follows: 11 restricting type (AN-R), nine binge-eating and purging type (AN-BP). Subjects underwent an oral glucose tolerance test at 08.00 h. Blood was collected 0, 30, 60, 120 and 180 min after the glucose load. RESULTS: Both AN-R and AN-BP had a significant increased basal ghrelin level (P < 0.01) and a significantly decreased basal insulin level (P < 0.05) as compared to controls. The time of the nadir of mean ghrelin in AN-BP (120 min, 58.1% of basal level, 204.9 +/- 34.3 pmol/l, mean +/- SEM) was delayed compared to controls (60 min, 60.2%, 74.3 +/- 7.9 pmol/l), and in the AN-R group it kept decreasing for 180 min (80.0%, 182.4 +/- 31.5 pmol/l). The peaks insulin levels in AN-BP (120 min, 319.3 +/- 88.8 pmol/l) and AN-R (180 min, 418.9 +/- 68.4 pmol/l) were also delayed as compared to controls (60 min, 509.2 +/- 88.8 pmol/l). The glucose level at 180 min in AN-R was significantly (P < 0.05) higher than in controls. CONCLUSIONS: These findings suggest that differences in eating behaviour in AN may induce alterations in both ghrelin and insulin metabolism in the acute feeding state. Furthermore, metabolic changes in the restrictive eating pattern may be related to the pathophysiology of small quantitative meal intake in AN-R patients.

A characteristic reactive hypoglycemia induced by rapid change of eating behavior in anorexia nervosa: a case report.

UNLABELLED: The relationship among reactive hypoglycemia, corresponding insulin metabolism, and eating behavior in anorexia nervosa (AN) has not been well documented. METHOD: A 22-year-old woman with AN was admitted to Kagoshima University Hospital. An oral glucose tolerance test was performed with additional sampling at 15 minutes on the seventh hospital day when her daily caloric intake rapidly increased, reaching 2,000kcal perday. RESULTS: An elevated level of insulin secretion (1,190pmol/L) was observed during the very early phase (15 minutes) after glucose load, whereas corresponding blood glucose elevations were not as high (1.2mmol/L). The patient experienced asymptomatic hypoglycemia (2.1mmol/L). CONCLUSIONS: Our findings suggested that a rapid increase of energy intake might cause reactive hypoglycemia with characteristic insulin metabolism, that is, an elevated level of insulin secretion during the very early phase.

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.

Insulinogenic index at 15 min as a marker of nutritional rehabilitation in anorexia nervosa.

BACKGROUND: Insulin responses to the oral-glucose-tolerance test (OGTT) in anorexia nervosa (AN) are related to body weight and show various patterns. Although weight gain is a key indicator of a successful nutritional program, it is not a sufficiently accurate index for assessing nutritional status, especially in the periods of marked fear of obesity, because patients often manipulate body weight measurements. OBJECTIVE: The aim of this study was to determine the relation between insulin metabolism during the early phase of the OGTT and progress (weekly weight gain) during nutritional rehabilitation. DESIGN: Forty-eight inpatients with AN (25 AN restricting type and 23 AN bulimic type) underwent the OGTT, with additional blood sampling at 15 min, when energy intake reached 6694 kJ/d (1600 kcal/d). Thirteen healthy volunteers were also studied. To evaluate early-phase insulin metabolism, we calculated the insulinogenic index after 15 (II(15 min)) and 30 min. On the basis of weekly changes in body weight, the AN participants were divided into good (> or =0.5 kg) and poor (<0.5 kg) responders. RESULTS: Among the AN patients, 48% were poor responders. Analysis of variance showed significant differences in the II(15 min) values (P = 0.0005) and showed that II(15 min) values for good responders were significantly higher than those for the other groups. CONCLUSIONS: These findings suggest that a lack of progress in weight gain is frequently observed in AN and that II(15 min) values may be a useful marker with which to assess the weekly progress during nutritional rehabilitation.

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.

Increased fasting plasma ghrelin levels in patients with bulimia nervosa.

OBJECTIVE: Fasting plasma ghrelin levels play an important role in the pathophysiology of the eating disorder anorexia nervosa. Bulimia nervosa (BN) also has been associated with abnormal neuroendocrine regulation. Thus, we examined the relationship between body mass index (BMI) and plasma ghrelin concentrations in patients with BN for the first time. METHODS: The subjects included 15 female BN patients and 11 female healthy volunteers (controls). Fasting blood samples were collected from all subjects. RESULTS: The plasma ghrelin concentrations in all subjects demonstrated a significantly negative correlation with BMI. Mean plasma ghrelin level in BN patients was significantly higher than that in the controls, though mean BMIs between the groups were not significantly different. CONCLUSION: These findings suggest that not only BMI but also abnormal eating behaviors with habitual binge eating and purging may have some influence on circulating ghrelin level in BN.

Emotional stress and brux-like activity of the masseter muscle in rats.

The aim of this study was to further clarify the relationship between emotional stress and bruxism. In experiment 1, 60 male 9-week-old Wistar rats were divided into four groups: the emotionally stressed (ES), the emotionally non-stressed (NS), the electrically foot-shocked (FSd), and the non-foot-shocked (NSd). ES rats were confined in a communication box for one hour a day to observe the emotional responses of neighbouring FSd rats. On days 0, 1, 4, 8, and 12, the electromyographic activity of the ES and NS rats' left masseter muscles was recorded for one hour, three hours after confinement in the communication box. Brux-like activity appeared in the masseter muscle of the ES group on days 1, 4, 8, and 12, but not in the NS group. In experiment 2, 36 male Wistar rats, 9 weeks old, were divided into three groups: emotionally stressed rats treated with an anti-anxiety drug (DES), emotionally stressed rats treated with saline as a vehicle (VES), and 24 FSd rats. Stress and EMG procedures were the same as those in experiment 1. Brux-like episodes decreased in DES rats from day 1 and significant differences were found on days 4 (P < 0.01), 8 (P < 0.05), and 12 (P < 0.05), when compared with the VES group. These findings suggest that emotional stress induces brux-like activity in the masseter muscle of rats, which was reduced with anti-anxiety drugs.

Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion.

Ghrelin, a novel GH-releasing peptide isolated from human and rat stomach, stimulates food intake and GH secretion. We determined plasma ghrelin concentrations in patients with simple obesity, anorexia nervosa, and type 2 diabetes mellitus by RIA. We also studied plasma ghrelin responses to glucose load and meal intake and obtained a 24-h profile of circulating ghrelin in humans. Plasma ghrelin concentrations in patients with simple obesity and anorexia nervosa were lower and higher, respectively, than those of healthy subjects with normal body weight. Among those with type 2 diabetes mellitus, obese patients had lower and lean patients higher fasting plasma ghrelin concentrations than normal-weight patients. Fasting plasma ghrelin concentration was negatively correlated with body mass index in both nondiabetic and diabetic patients. Plasma ghrelin concentrations of normal subjects decreased significantly after oral and iv glucose administration; a similar response was also observed in diabetic patients after a meal tolerance test, reaching a nadir of 69% of the basal level after the meal. Circulating plasma ghrelin showed a diurnal pattern with preprandial increases, postprandial decreases, and a maximum peak at 0200 h. This study demonstrates that nutritional state is a determinant of plasma ghrelin in humans. Ghrelin secretion is up-regulated under conditions of negative energy balance and down-regulated in the setting of positive energy balance. These findings suggest the involvement of ghrelin in the regulation of feeding behavior and energy homeostasis.