Keisuke Kawai

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty‐six eating disorder patients, including 131 anorexia nervosa (AN)‐restricting types (AN‐R), 97 AN‐binge eating/purging types (AN‐BP) and 108 bulimia nervosa (BN)‐purging types (BN‐P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D′ = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN‐P (allele‐wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72‐3056C in BN‐P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN‐P.

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: A cross-sectional and prospective study

BackgroundThis cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes.MethodsParticipants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined.ResultsBaseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c.ConclusionThe DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.

Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa.

BackgroundPatients 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.MethodAll 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.ResultsIn 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.ConclusionThe 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.

The relationship between the age of onset of type 1 diabetes and the subsequent development of a severe eating disorder by female patients.

Takii M, Uchigata Y, Kishimoto J, Morita C, Hata T, Nozaki T, Kawai K, Iwamoto Y, Sudo N, Kubo C. The relationship between the age of onset of type 1 diabetes and the subsequent development of a severe eating disorder by female patients.

Psychopathological features of anorectic patients who dropped out of inpatient treatment as assessed by the Minnesota Multiphasic Personality Inventory

BackgroundAnorexia nervosa often requires inpatient treatment that includes psychotherapeutic intervention in addition to physical and nutritional management for severe low body weight. However, such patients sometimes terminate inpatient treatment prematurely because of resistance to treatment, poor motivation for treatment, unstable emotions, and problematic behaviors. In this study, the psychopathological factors related to the personality of anorexic patients that might predict discontinuation of inpatient treatment were investigated using the Minnesota Multiphasic Personality Inventory (MMPI).MethodsSubjects were 75 consecutive anorectic inpatients who received cognitive behavioral therapy with a behavior protocol governing privileges in a university hospital based general (not psychiatric) ward. The MMPI was done on admission for all patients. A comparison was done of patients who completed the process of inpatient treatment, including attainment of target body weight (completers), and patients who dropped out of inpatient treatment (dropouts). Results: No significant differences between completers (n = 51) and dropouts (n = 24) were found in the type of eating disorder, age of onset, duration of illness, age, or BMI at admission. Logistic regression analysis found the MMPI scales schizophrenia (Sc), hypomania (HYP), deviant thinking and experience, and antisocial attitude to be factors predicting completion or dropout.ConclusionDropouts have difficulty adapting to inpatient treatment protocols such as our behavior protocol governing privileges because they have social and emotional alienation, a lack of ego mastery (Sc), emotional instability (HYP) and an antisocial attitude. As a result, they have decreased motivation for treatment, leave the hospital without permission, attempt suicide, or shoplift, which leads them to terminate inpatient treatment prematurely. Treatments based on cognitive behavioral therapy with a behavior protocol governing privileges should be carefully adopted for anorectic patients who exhibit the psychopathological elements identified in this study.

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

Background Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. Methods Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T→C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Coxs proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. Results Patients with the TT genotype at 3056 T→C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. Conclusion The 3056 T→C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

Predictors of menstrual resumption by patients with anorexia nervosa

Objective: To investigate which factors predict the resumption of menstruation by patients with anorexia nervosa (AN). METHODS: Participants were AN patients who, even after weight recovery by inpatient treatment, had prolonged amenorrhea (N=11), AN patients who resumed menstruation after weight recovery (N=9), and age-matched healthy controls (N=12). Anthropometric data and the serum levels of leptin, insulin-like growth factor I (IGF-1), cortisol, luteinizing hormone (LH), estradiol (E2), and other hormones were measured at the beginning of the inpatient treatment and after weight recovery. RESULTS: Of the baseline anthropometric and hormonal factors, logistic regression analysis extracted a high serum cortisol level as a predictor of the inhibition of the resumption of menstruation. After weight recovery, the E2 and leptin levels were significantly higher for eumenorrheic patients than for amenorrheic patients. CONCLUSION: The baseline serum cortisol level was a predictor of the prolonged inhibition of menstrual recovery.

BMI, body composition, and the energy requirement for body weight gain in patients with anorexia nervosa

OBJECTIVE Theories abound about the energy requirements for body weight gain in anorexia nervosa (AN). We hypothesized that malnutrition status affects the energy requirements. METHOD On admission, 97 AN patients were measured for body composition by dual-energy X-ray absorptiometry. The relationship between body mass index (BMI) and body composition was investigated. In addition, 21 patients who completed our treatment program were tested for energy intake and body weight. RESULTS The relationship between BMI and both fat-free mass and fat mass (FM) on admission was curvilinear. The weight gain per excess energy was greater in the group of patients with FM < 4 kg or BMI < 14 kg/m(2) than in the group with FM > or = 4 kg or BMI > or = 14 kg/m(2) (p = .037, p = .055, respectively). DISCUSSION The energy requirements for weight gain in AN patients are related to the initial FM and BMI.

Somatic and psychological factors related to the body mass index of patients with anorexia nervosa.

Objective: The aim of this study was to examine somatic and psychological factors related to the body mass index (BMI) of anorexia nervosa (AN) patients. Method: The analysis was of 24 hospitalized AN patients from the day after admission to the 4th day. The somatic factors analyzed were duration of AN, daily food intake, eating regulatory substances in blood (acylated ghrelin, desacyl ghrelin, leptin), serum cortisol, insulin and estimated creatinine clearance (CCr). The psychological factors analyzed were depression, anxiety, Eating Disorder Inventory (EDI), and hunger/fullness feeling. Measurement of BMI and collection of blood samples were done on the morning after hospitalization. Statistical analysis was by multiple linear regression analysis. Results: BMI showed a reverse correlation with desacyl ghrelin (β=-0.486, p=0.015) and maturity fears (β=-0.375, p=0.046), but was not associated with any other factor by multiple regression analysis. Conclusion: The results suggest that desacyl ghrelin and maturity fears play important roles in the prolonged malnutrition state seen in AN patients.

No association of brain‐derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese

The Met66 allele of the Val66Met polymorphism in the brain‐derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785–1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one‐way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.