Prediction of impending type 1 diabetes through automated dual-label measurement of proinsulin:C-peptide ratio

Background : The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin: C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release. Methods : Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (Auto Delfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive firstdegree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range). Results : TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r(2) = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day % CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated ( r(s) = -0.596; P<0.001) with first-phase C-peptide release during clamp ( also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release. Conclusions : The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test

Parenting and treatment adherence in type 1 diabetes throughout adolescence and emerging adulthood

Objective. To examine the role of diabetes-specific parental and general parenting dimensions (responsiveness and psychological control) in treatment adherence throughout adolescence and emerging adulthood. Methods. 521 patients (aged 14-25 years) with Type 1 Diabetes (T1D), 407 mothers, and 345 fathers were included. Analyses within and across informants examined the associations between the parenting variables and treatment adherence (and potential moderation effects in these associations). Results. Lower psychological control and higher parental responsiveness were associated with better treatment adherence. Diabetes-specific parental regulation was not linked to treatment adherence, except when combined with high levels of responsiveness. Some effects of psychological control and responsiveness were more pronounced in the older age group. Conclusions. Researchers and clinicians should remain attentive to the potential role of parenting for treatment adherence, even in emerging adult patients.status: publishe

Evaluation of an Immunoturbidimetric Assay for Haemoglobin A1c on a Cobas® Mira S Analyser

Peer Reviewe

Fluctuating asymmetry in dental and mandibular nonmetric traits as evidence for childcare sex bias in 19th/20th century Portugal.

Fluctuating asymmetry, often considered a measure of developmental instability, was studied in the dental morphological traits of 600 individuals from among the poorest sectors of society in 19th-20th century Portugal. The aims are to identify and interpret any differences between: (1) males and females, and (2) patterns of distribution among teeth with different odontogenic timings, to assess if any sex bias existed in childcare. Dental and mandibular morphological traits were recorded using the Arizona State University Dental Anthropology System. z-Ratios were used to compare summed absolute fluctuating asymmetry frequencies between sexes and age groups. Results from rank correlation coefficients ruled out directional asymmetry and antisymmetry, based on positive (>0.2) bilateral association of traits in larger samples. Sex differences were significant (z-ratio=3.128; p=0.0018), while age differences were not (z-ratio=-0.644; p=0.5196). Teeth forming after infancy tended to be more asymmetric in females. Potential reasons for the sex difference include: (1) greater female susceptibility to developmental instability, (2) greater male childhood mortality that yields lower fluctuating asymmetry in surviving males, and/or (3) cultural bias favoring male access to resources. Results suggest the latter hypothesis is most likely, as fluctuating asymmetry is enhanced during childhood, perhaps coinciding with gender role definitions. There seems to be no association between asymmetry and early mortality in males. A lack of parallels in prior research renders differential sex reaction to environmental stress dubious. This population may have favored male children in their access to appropriate conditions for development

BMI is an important driver of beta-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children.

OBJECTIVE: Body weight-related insulin resistance probably plays a role in progression to type 1 diabetes, but has an uncertain impact following diagnosis. In this study, we investigated whether BMI measured at diagnosis was an independent predictor of C-peptide decline 1-year post-diagnosis. DESIGN: Multicentre longitudinal study carried out at diagnosis and up to 1-year follow-up. METHODS: Data on C-peptide were collected from seven diabetes centres in Europe. Patients were grouped according to age at diagnosis (5 years 10 years 18 years, n=410). Linear regression was used to investigate whether BMI was an independent predictor of change in fasting C-peptide over 1 year. Models were additionally adjusted for baseline insulin dose and HbA1c. RESULTS: In individuals diagnosed between 0 and 5 years, 5 and 10 years and those diagnosed >18 years, we found no association between BMI and C-peptide decline. In patients aged 10-18 years, higher BMI at baseline was associated with a greater decline in fasting C-peptide over 1 year with a decrease (beta 95% CI; P value) of 0.025 (0.010, 0.041) nM/kg per m(2) higher baseline BMI (P=0.001). This association remained significant after adjusting for gender and differences in HbA1c and insulin dose (beta=0.026, 95% CI=0.0097, 0.042; P=0.002). CONCLUSIONS: These observations indicate that increased body weight and increased insulin demand are associated with more rapid disease progression after diagnosis of type 1 diabetes in an age group 10-18 years. This should be considered in studies of beta-cell function in type 1 diabetes

Anodal transcranial direct current stimulation (tDCS) over the left DLPFC improves emotion regulation

peer reviewedThe study of emotion regulation constitutes a major area of research for having a complete picture of human emotional experience, and several lines of evidence claim that poor emotion regulation skills are particularly deleterious in different aspects of life. Previous tDCS studies have suggested the beneficial role of DLPFC stimulation to improve emotion processing and regulation. The present study was therefore conducted to confirm and extend the effects of DLPFC stimulation on emotion regulation by including both positive and negative emotional material. In this between subjects study, participants were randomly assigned to receive active or sham stimulation over the left DLPFC. Participants viewed negative, positive, and neutral pictures while attempting to decrease, increase, or not modulate their emotional reactions. Subjective reactions were assessed via on-line ratings. The main results show that anodal tDCS stimulation over the left DLPFC slightly improves the ability to increase emotion perception for positive emotions. More interestingly, the results demonstrate that tDCS enhances the regulation of both positive and negative emotions when the baseline is considered. This study provides additional data on the use of tDCS as a tool to increase emotion regulation not only for negative affective material, but also for positive ones

Rogers v. Robson: Increased Malpractice Liability for Insurance Defense Counsel, 14 J. Marshall L. Rev. 589 (1981)

Poster Presentationstatus: publishe

Audit Tendering in the UK: A Review of Stakeholders’ Views

This study reports the results of a content analysis of the comment letters sent to the UK Financial Reporting Council (FRC), in response to its consultation document on the 2012 revisions of the UK Corporate Governance Code, concerning the proposal for mandatory audit tendering. The results indicate a general support for the FRC’s proposals with a number of key concerns related to audit quality, auditor independence and audit cost. There is also clear conflict of interests among some stakeholder groups such as audit firms and companies on one side and institutional investors on the other side. There is evidence of conflict of interest between Big 4 and non-Big 4 audit firms. Implications for future consultations and legislations are also discussed

Parental illness intrusiveness and youth glycaemic control in type 1 diabetes : intergenerational associations and processes

Objective: This study examined associations between the functioning of youth with type 1 diabetes and their parents, including parenting dimensions as intervening mechanisms. The study adds to the existing literature by focusing on (1) the concept of parental illness intrusiveness; (2) the (understudied) periods of adolescence and emerging adulthood; and (3) maternal and paternal functioning. Design: Questionnaires were completed by 317 patient-mother dyads and 277 patient-father dyads. All patients (aged 14–25) had type 1 diabetes. The hypothesised model was compared to an alternative model using structural equation modelling. Main Outcome Measures: Youth reported on depressive symptoms and treatment adherence; Physicians provided HbA1c-values. Parents reported on illness intrusiveness, depressive symptoms, and their child’s treatment adherence. Patients and parents reported on psychological control and overprotection. Results: The hypothesised path model had a good fit to the data. Parental illness intrusiveness was positively associated with depressive symptoms and both were positively related to overprotection and psychological control. Psychological control was positively related to patients’ depressive symptoms and negatively to treatment adherence. Poorer treatment adherence was associated with worse HbA1c-values. Conclusion: These findings underscore the relevance of parental illness intrusiveness and emphasise the importance of mothers’ and fathers’ roles throughout adolescence and emerging adulthood.status: publishe

Excess cardiovascular risk in diabetic women: a case for intensive treatment.

Diabetes is a common and rapidly growing disease that affects more than 380 million people worldwide and is an established risk factor for cardiovascular disease with differential effects on women compared to men. While the general population of women, particularly young women, has more favourable cardiovascular risk profiles than men, this protective effect has been shown to be lost or even reversed in diabetic women. Several studies have demonstrated a significant diabetes-associated excess risk of cardiovascular disease in women. Sex-specific differences in risk factors associated with diabetes and their management may be responsible for the relative excess cardiovascular risk in women with diabetes. Diabetic women need intensive treatment in order to optimize management of cardiovascular risk factors. Further studies are needed to elucidate the mechanisms underlying the excess cardiovascular risk in diabetic women in order to tailor prevention and treatment strategies