ObjectiveGrowing qualitative evidence reveals that many patients with chronic illnesses struggle to rebuild a positive self-image after diagnosis while attempting to find a balance between their current physical status and their ongoing social duties. One factor destabilizing patients’ identities is self-stigma, which seems to affect their behavioral goals through decreased self-efficacy. We hypothesized that self-stigma would be an independent factor, distinct from self-efficacy, for developing self-care behaviors in patients with type 2 diabetes.MethodsWe used a consecutive sample of 209 outpatients with type 2 diabetes treated by endocrinologists at two university hospitals, one general hospital and one clinic. We performed multiple linear regression analyses to test the relationship between the patients’ activation levels for self-care behaviors (dependent variable) and self-stigma, self-efficacy, and depression symptoms (independent variables), adjusting for covariates involving sociodemographic and clinical characteristics.ResultsIn a multiple linear regression model adjusted for prior covariates, there was significant association between self-stigma and activation levels for self-care behaviors in patients with type 2 diabetes (adjusted R2=0.26, F (12,196)=7.20, p<0.001). The standardized partial regression coefficient of self-stigma was −0.23 (p=0.001), whereas that of self-efficacy was 0.19 (p=0.007).ConclusionsSelf-stigma is a negative independent factor, separate from self-efficacy, affecting the self-care behaviors of patients with type 2 diabetes. Self-stigma also has, at least, a similar impact on self-care behaviors to that of self-efficacy. To optimize treatment outcomes, patients’ self-stigma should be minimized, whereas their self-efficacy should be enhanced.

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ABSTRACT:We have identified several novel metabolites of ticlopidine, a well known antiplatelet agent and have revealed its metabolic route in rats. The main biliary metabolite of ticlopidine was characterized as a glutathione (GSH) conjugate of ticlopidine S-oxide, in which conjugation had occurred at carbon 7a in the thienopyridine moiety. Quantitative analysis revealed that 29% of the dose was subjected to the formation of reactive intermediates followed by conjugation with GSH after oral administration of ticlopidine (22 mg/ kg) to rats. In vitro incubation of ticlopidine with rat liver 9000g supernatant fraction (S9) fractions led to the formation of multiple metabolites, including 2-oxo-ticlopidine, the precursor for the pharmacologically active ticlopidine metabolite, [1-(2-chlorobenzyl)-4-mercaptopiperidin-(3Z)-ylidene] acetic acid. A novel thiophene ring-opened metabolite with a thioketone group and a carboxylic acid moiety has also been detected after incubation of 2-oxo-ticlopidine with rat liver microsomes or upon incubation of ticlopidine with rat liver S9 fractions.Ticlopidine is a well known antiplatelet agent (Quinn and Fitzgerald, 1999) and has been widely used for the secondary prevention of atherothrombosis (Jacobson, 2004). The metabolism of ticlopidine is complex because of extensive oxidation in the liver (Saltiel and Ward, 1987). For example, less than 1% of the parent compound was detected in urine, whereas approximately 60 and 25% of radioactivity was recovered in urine after a single oral administration of [ 14 C]ticlopidine to humans (Noble and Goa, 1996) and rats (Tuong et al., 1981), respectively. Furthermore, a large difference was observed between the total radioactivity and unchanged ticlopidine level in the plasma (Panak et al., 1983). In the 1980s, metabolic studies suggested that N-dealkylation, N-oxidation, and oxidation of the thiophene ring followed by ring opening appeared to be the main routes, but numerous highly polar urinary and biliary metabolites in both humans and animals remained unidentified (Tuong et al., 1981;Panak et al., 1983). More recently, novel ticlopidine metabolites such as the S-oxide form (Ha-Duong et al., 2001) and the pharmacologically active metabolite (Yoneda et al., 2004) have been detected. However, the whole metabolism of ticlopidine has remained unclarified.In the present study, we have identified several novel metabolites of ticlopidine and revealed the metabolic pathways of ticlopidine quantitatively. Moreover, an in vitro experiment was conducted to elucidate the whole metabolic route of ticlopidine including the biotransformation to the pharmacologically active metabolite.

ObjectivesSelf-stigma is associated with lower patient activation levels for self-care in persons with type 2 diabetes mellitus (T2DM). However, the causal pathway linking self-stigma with patient activation for self-care has not been shown. In order to determine how self-stigma affects patient activation for self-care, we tested a two-path hypothetical model both directly and as mediated by self-esteem and self-efficacy.DesignA cross-sectional study.SettingTwo university hospitals, one general hospital and one clinic in Japan.ParticipantsT2DM outpatients receiving treatment (n=209) completed a self-administered questionnaire comprising the Self-Stigma Scale, Patient Activation Measure, Rosenberg Self-Esteem Scale, General Self-Efficacy Scale, Patient Health Questionnaire, haemoglobin A1c test, age, sex and body mass index.Primary and secondary outcome measuresSelf-stigma levels were measured by using the Self-Stigma Scale. Patient activation levels were measured by the Patient Activation Measure.ResultsPath analysis showed a strong relationship between self-stigma and patient activation (χ2=27.55, p=0.120; goodness-of-fit index=0.97; adjusted goodness-of-fit index=0.94; comparative fit index=0.98; root mean square error of approximation=0.04). Self-stigma had a direct effect on patient activation (β=−0.20; p=0.002). Indirectly, self-stigma affected patient activation along two paths (β=0.31; p<0.001) by reducing self-esteem (β=−0.22; p<0.001) and self-efficacy (β=−0.36; p<0.001).ConclusionsDue to the cross-sectional design of the study, longitudinal changes between all the variables cannot be established. However, the findings indicate that self-stigma affected patient activation for self-care, both directly and as mediated by self-esteem and self-efficacy. Interventions that increase self-esteem and self-efficacy may decrease self-stigma in patients with T2DM, thus increasing patient activation for self-care.

ObjectivesThe aim of this study was to test the psychological and behavioural patterns of stigma (self-esteem and social participation) and their relationship to self-stigma, patient activation for engaging in self-care and glycaemic control among patients with type 2 diabetes mellitus (T2DM).DesignA cross-sectional study.Setting2 tertiary-level hospitals and 2 secondary-level hospitals in Japan.ParticipantsA consecutive sample of 209 outpatients with T2DM. Inclusion criteria were as follows: presence of T2DM, age 20–74 years, no diagnosis of dementia and/or psychosis, and no need for urgent medical procedures.Outcome measuresStudy measures included a self-administered questionnaire to assess the Rosenberg Self-Esteem Scale (SES), the 3 subscales of 36-question Short Form Health Survey (SF-36; Social Function, Role Physical, Role Emotional), Self-Stigma Scale and Patient Activation Measure (PAM-13). Glycated haemoglobin was obtained from same day blood work. In our previous qualitative study, we found that psychological and behavioural patterns of stigma varied according to patients' levels of illness-related self-esteem as well as attitudes towards social participation. For quantitative consistency, we used the SES scale to measure self-esteem and the SF-36 subscales to measure social participation. We then divided participants into 4 groups by exhibited psychological and behavioural patterns: group A (high SES/high SF-36), group B (high SES/low SF-36), group C (low SES/high SF-36) and group D (low SES/low SF-36).ResultsUsing analysis of covariance after controlling for age and sex, there was a significant difference in self-stigma levels between the four groups (F[3203]=15.70, p<0.001). We observed the highest mean self-stigma levels in group D. Group D also had significantly lower PAM-13 scores than those of groups A (p<0.001) and B (p=0.02).ConclusionsThe psychological and behavioural pattern of group D was found to be associated with higher levels of self-stigma and poorer patient activation for self-care.