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PURPOSE: The aim of the present study was to evaluate the role of ejection fraction (EF), left ventricular (LV) global longitudinal strain (LVGLS) and global constructive work (GCW) as prognostic variables in patients with cardiac amyloidosis (CA). METHODS: CA patients were retrospectively identified between 2015 and 2021 at a tertiary care hospital. Comprehensive clinical, biochemical, and imaging evaluation including two-dimensional (2D) echocardiography with myocardial work (MW) analysis was performed. A clinical combined endpoint was defined as all-cause mortality and heart failure readmission. RESULTS: 70 patients were followed for 16 (7-37) months and 37 (52.9%) reached the combined endpoint. Patient with versus without clinical events had a significantly lower LVEF (40.71% vs. 48.01%, p = 0.039), LVGLS (-9.26 vs. -11.32, p = 0.034) and GCW (1034.47mmHg% vs. 1424.86mmHg%, p = 0.011). Multivariable analysis showed that LVEF ( odds ratio (OR): 0.904; 95% confidence interval (CI): 0.839-0.973, p = 0.007), LVGLS ( OR: 0.620; 95% CI: 0.415-0.926, p = 0.020) and GCW ( OR: 0.995; 95% CI: 0.990-0.999, p = 0.016) were significant predictors of outcome, but the model including GCW had the best discriminative ability to predict the combined endpoint (C-index = 0.888). A GCW less than 1443mmHg% was able to predict the clinical endpoint with a sensitivity of 94% and a specificity of 64% (Area under the curve (AUC): 0.771 (95% CI: 0.581-0.961; p = 0.005)). CONCLUSION: In CA patients, GCW may be of additional prognostic value to LVEF and GLS in predicting heart failure hospitalization and all-cause mortality.

Background Islet cell-specific autoantibodies are useful to classify diabetes. The aim of this study was to evaluate the performance of commercially available ELISAs to detect autoantibodies to glutamic acid decarboxylase 65-kDa isoform (GADA), tyrosine phosphatase-related islet antigen 2 (IA-2A), zinc transporter protein 8 (ZnT8A), and insulin (IAA). The performance of ELISA was compared to the performance of RIA. Methods We retrospectively identified 76 newly diagnosed type 1 diabetes mellitus patients (median age 27 years, female/male: 0.65) and 131 disease controls (median age 45 years, female/male: 0.60). The ELISAs were from Medipan. RIAs were in-house methods from the Belgian Diabetes Registry or from Medipan or DIASource. Results Sensitivity and specificity of ELISA were, respectively, 97% and 97% for GADA, 61% and 99% for IA-2A, 1% and 96% for IAA, and 70% and 98% for ZnT8A. The likelihood ratio for type 1 diabetes increased with increasing antibody levels for GADA, IA-2A, and ZnT8A measured by ELISA. The positive predictive value of double positivity for either GADA, IA-2A, or ZnT8A was 100%. Conclusions The ELISAs to detect GADA, IA-2A, and ZnT8A have good performance characteristics. Combining autoantibody assays and taking into account antibody levels improves the interpretation of autoantibody testing.

PurposeHyperuricemia in childhood obesity associates variably with distinct components of the metabolic syndrome. We aimed to investigate the prevalence of hyperuricemia in an ethnically diverse pediatric obese population in Brussels using age and sex-specific serum uric acid (SUA) reference ranges.Methods We performed a cross-sectional analysis of data from overweight/obese children at Universitair Ziekenhuis Brussel between 2013 and 2017. Hyperuricemia was defined by a SUA above the assay specific and age and gender defined reference range. Results Among 388 children and adolescents, 9% were overweight, 16.2% had class I obesity, 27.8% had class II obesity and 46.9% had class III obesity. Median SUA was 4.8 mg/dL, with 20.6% patients showing an elevated SUA. Degree of general and central obesity, pubertal status, gender, descent and the presence of metabolic syndrome and insulin resistance were not significantly different between those with and without hyperuricemia. Median waist-to-height ratio, serum triglycerides and insulin resistance were significantly higher in Turkish children compared to children of other descent. Conclusion Hyperuricemia was not associated with age, ethnicity, severity of global/central obesity, metabolic syndrome or its components. Future studies should focus on investigating the association with diet composition, obesity duration and the eventual risk for cardiovascular complications.

Between 19 May and 12 June 2020, employees of the UZ Brussel were recruited in this study aiming to document the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence, to investigate the potential work-related risk factors for SARS-CoV-2 infection and to estimate the proportion of asymptomatic infections. In total, 2662 participants were included of whom 7.4% had immunoglobulin G antibodies against SARS-CoV-2. Of the participants reporting a positive polymerase chain reaction for SARS-CoV-2, 89% had antibodies at the time of blood sampling. Eleven per cent of the antibody positive participants reported no recent symptoms suggestive of coronavirus disease 2019 (COVID-19). Participants reporting fever, chest pain and/or anosmia/ageusia were significantly more frequently associated with the presence of antibodies against SARS-CoV-2. The presence of antibodies was highest in the group that had had contact with COVID-19-infected individuals outside the hospital with or without using appropriate personnel protective equipment (PPE) (P < 0.001). Inside the hospital, a statistically significant difference was observed for the employees considered as low-risk exposure compared to the intermediate-risk exposure group (P = 0.005) as well as the high-risk exposure group compared to the intermediate exposure risk group (P < 0.001). These findings highlight the importance of using correct PPE.

OBJECTIVES: Prior research has linked illness identity-or the extent to which the illness is integrated into one's identity-to diabetes-specific functioning. Four illness identity dimensions have been identified: rejection, acceptance, engulfment, and enrichment. As longitudinal research on this topic is scarce, this study examined developmental trajectories of illness identity and prospective associations between illness identity and diabetes-specific functioning. METHOD: Adolescents and emerging adults with Type I diabetes, aged 14 to 25 (Mage = 19; 54% girls), participated in a four-wave longitudinal study spanning 3 years (N = 559 at Time 1). Participants filled out questionnaires on illness identity, treatment adherence, and diabetes-specific distress. Hemoglobin A1c (HbA1c) values were obtained from participants' medical records. To chart the development of illness identity over time, we performed latent growth curve modeling. Cross-lagged analysis was used to examine prospective associations between illness identity and diabetes-specific functioning. RESULTS: We observed small linear increases in acceptance (Mslope = .05, p < .01) and engulfment (Mslope = .03, p < .05) and a small linear decrease in rejection (Mslope = -.08, p < .001) across waves (with scale scores ranging between 1 and 5). Rejection negatively predicted and enrichment positively predicted treatment adherence 1 year later, which, in turn, positively predicted enrichment and negatively predicted engulfment over time. Furthermore, rejection and engulfment positively predicted diabetes-specific distress 1 year later. Finally, diabetes-specific distress and HbA1c positively predicted engulfment 1 year later. Standardized cross-lagged coefficients ranged between |.05| and |.11|. CONCLUSIONS: We identified small but interesting changes in three out of four illness identity dimensions. Prospective associations between illness identity and diabetes-specific functioning were bidirectional in nature. (PsycInfo Database Record (c) 2021 APA, all rights reserved). ispartof: HEALTH PSYCHOLOGY vol:40 issue:5 pages:326-336 ispartof: location:United States status: published

Background/aimsSARS-CoV-2 is highly contagious. More evidence concerning extrapulmonary transmission routes such as the eyes is urgently needed. Although the humoral immune response is important in the viral containment, the local response in tears has not yet been studied. The aim of our study was twofold: to assess the prevalence of both SARS-CoV-2 RNA and antibodies in tear fluid.MethodsIn a first series, nasopharyngeal sampling and tear sampling by Schirmer test strips were performed in 26 acutely ill patients with COVID-19 to assess the presence of SARS-CoV-2 RNA by reverse transcription PCR. In a second series, IgG and IgA responses to SARS-CoV-2 spike protein in serum and tear fluid of convalescent individuals (n=22) were compared with control individuals (n=15) by ELISA.ResultsSARS-CoV-2 RNA was detected in tears of 7/26 (26.9%) patients with COVID-19. None of them had ocular symptoms. Convalescent individuals displayed a significant higher ratio of IgG (pConclusionsOur results demonstrate the presence of SARS-CoV-2 RNA and a local IgG and IgA immune response in tear fluid. These data confirm the possibility of SARS-CoV-2 transmission through tear fluid and the importance of the eye as a first defence against SARS-CoV-2, indicating the potential of tears as a non-invasive surrogate for serum in monitoring the host immune response.

Objectives To evaluate the diagnostic performances of four SARS-CoV-2 IgG antibody immunoassays. Methods Following immunoassays were studied: Abbott's SARS-CoV-2 IgG assay, Diasorin's Liaison SARS-CoV-2 S2/S2 IgG assay, Euroimmun's Anti-SARS-CoV-2 IgG ELISA, and Roche's Elecsys Anti-SARS-CoV-2 assay. Specificity was retrospectively evaluated with 38 samples from 2019. Sensitivity samples (n = 147) were taken from SARS-CoV-2 real-time PCR-positive patients who developed COVID-19 symptoms ten days earlier. Results Mean specificity was 96.6%. Mean sensitivity was 62.7% from ten days after onset of symptoms, 84.4% from 15 days after onset of symptoms, and 87.5% from 20 days after onset of symptoms. Conclusions Specificity was high, while Abbott and Roche were 100% specific. Sensitivity increased over time, with Abbott and Roche having the highest sensitivity at all time points with ≥90% from 20 days after symptoms' onset. These findings may assist in selecting SARS-CoV-2 IgG antibody immunoassays for additional diagnostics, epidemiological research, and vaccine development.

Autoantibodies against islet cell antigens are routinely used to identify subjects at increased risk of symptomatic type 1 diabetes, but their relation to the intra-islet pathogenetic process that leads to positivity for these markers is poorly understood. We screened 556 non-diabetic organ donors (3 months to 24 years) for five different autoantibodies and found positivity in 27 subjects, 25 single- and two double autoantibody-positive donors. Histopathological screening of pancreatic tissue samples showed lesion characteristic for recent-onset type 1 diabetes in the two organ donors with a high-risk profile, due to their positivity for multiple autoantibodies and HLA-inferred risk. Inflammatory infiltrates (insulitis) were found in a small fraction of islets (

Heat shock proteins (HSPs) play an essential role in protecting proteins from denaturation and are implicated in diverse pathophysiological conditions like cardiovascular diseases, cancer, infections, and neurodegenerative diseases. Scientific evidence indicates that if HSP expression falls below a certain level, cells become sensitive to oxidative damage that accelerates protein aggregation diseases. On the other hand, persistently enhanced levels of HSP can lead to inflammatory and oncogenic changes. To date, although techniques for measuring HSPs exist, these assays are limited for use in specific sample types or are time consuming. Therefore, in the present study, we developed a single-molecule assay digital ELISA technology (Single Molecule Array—SIMOA) for the measurement of HSPs, which is time effective and can be adapted to measure multiple analytes simultaneously from a single sample. This technique combines two distinct HSP-specific antibodies that recognize different epitopes on the HSP molecule. A recombinant human HSP protein was used as the standard material. The assay performance characteristics were evaluated by repeated testing of samples spiked with HSP peptide at different levels. The limit of detection was 0.16 and 2 ng/mL for HSP27 and HSP70, respectively. The inter- and intra-assay coefficients of variation were less than 20% in all tested conditions for both HSPs. The HSP levels assayed after serial dilution of samples portrayed dilutional linearity (on average 109%, R2 = 0.998, p < 0.001, for HSP27 and 93%, R2 = 0.994, p < 0.001, for HSP70). A high linear response was also demonstrated with admixtures of plasma exhibiting relatively very low and high levels of HSP70 (R2 = 0.982, p < 0.001). Analyte spike recovery varied between 57% and 95%. Moreover, the relative HSP values obtained using Western blotting correlated significantly with HSP values obtained with the newly developed SIMOA assay (r = 0.815, p < 0.001 and r = 0,895, p < 0.001 for HSP70 and HSP27, respectively), indicating that our method is reliable. In conclusion, the assay demonstrates analytical performance for the accurate assessment of HSPs in various sample types and offers the advantage of a huge range of dilution linearity, indicating that samples with HSP concentration highly above the calibration range can be diluted into range without affecting the precision of the assay.

OBJECTIVE: Type 1 diabetes in youth has a wide-ranging impact on families. This study aimed at a better understanding of experiences and difficulties that parents may encounter in their lives. Parental illness intrusiveness (ie, a parent's perception that the illness of one's child interferes with one's personal life) was prospectively examined in mothers and fathers. METHODS: Parental dyads (n = 291) completed four annual questionnaires on parental illness intrusiveness, depressive symptoms, and treatment adherence of their child. Youth reported on their treatment adherence. RESULTS: First, cross-lagged models showed that mothers' illness intrusiveness predicted relative increases in both mothers' and fathers' illness intrusiveness over time. Similar effects were found for fathers. Second, paired-samplest tests revealed higher illness intrusiveness in mothers at baseline. Latent growth curve modeling showed that mothers' illness intrusiveness generally decreased over time, while fathers' illness intrusiveness remained constant. Third, from a person-centered approach, multivariate latent class growth analysis identified three classes of parental couples: one with low and decreasing illness intrusiveness (54%), one with slightly elevated illness intrusiveness that remained stable over time (37%), and one with high illness intrusiveness that decreased in mothers but remained stable in fathers (9%). More parental depressive symptoms were reported in this latter class, while treatment adherence did not differ among the classes. CONCLUSIONS: Most parents in this sample reported rather low illness intrusiveness over time, yet some experienced a major impact of the illness. Examining parental illness intrusiveness may provide a better understanding of the specific challenges parents are confronted with. ispartof: PEDIATRIC DIABETES vol:21 issue:5 pages:890-899 ispartof: location:Denmark status: published

Little is known about the interplay between the autonomic nervous system and disease activity in multiple sclerosis (MS). We examined the relationship between heart rate variability (HRV), a reliable measure of vagal nerve function, and disease characteristics in a prospective MS cohort. Standard deviation of each normal-to-normal inter-beat interval (SDNN) and root mean square of successive differences (RMSSD), global indices of HRV, were measured in 114 MS patients, which included four predefined subgroups, and 30 age and sex-matched healthy controls (HC). We assessed group differences at baseline, HRV reproducibility at month 3, and used logistic regression modeling to relate baseline HRV with relapse occurrence. No significant HRV differences were found between MS and HC and between MS subgroups. In MS patients, both HRV indices correlated with age (r = &minus, 0.278, p = 0.018 and r = &minus, 0.319, p &lt, 0.001, respectively) and with month 3 assessments (r = 0.695 and r = 0.760, p &lt, 0.001). Higher SDNN and RMSSD at baseline were associated with self-reported relapses at month 3 (OR = 1.053, 95% CI (1.013&ndash, 1.095), p = 0.009 and OR = 1.065, 95% CI (1.016&ndash, 1.117), p = 0.009), and SDNN at baseline with relapses at month 12 (OR = 1.034, 95% CI (1.009&ndash, 1.059), p = 0.008, ROC, AUC = 0.733, p = 0.002). There were no baseline HRV differences between MS and HC or between subgroups. Post-hoc analysis showed an association with an increased relapse risk.

BackgroundDespite clear evidence that peers are crucial for youth development, research on the role of peers for youth with Type 1 diabetes (T1D) is scarce.PurposeThe present study identified trajectory classes of perceived peer functioning in youth with T1D, based on peer support and extreme peer orientation (EPO). Further, classes were compared with respect to their trajectories of depressive symptoms, diabetes-specific distress, treatment adherence, and HbA1c values.MethodsFive hundred and fifty-nine youth (14–25 years) with T1D completed questionnaires at baseline, 1, 2, and 3 years later. Latent class growth analysis identified classes of perceived peer functioning. Multigroup latent growth curve modelling assessed whether these classes were characterized by different trajectories of general and diabetes-specific functioning.ResultsA socially normative class (48%) was characterized by trajectories of high support and low EPO over time. A socially reserved class (29%) was characterized by low support and EPO, and a socially oriented class (17%) by high support and EPO. Finally, a socially vulnerable class (6%) was characterized by low support and high EPO. The normative class functioned significantly better over time than the other classes. The vulnerable class functioned significantly worse compared to the reserved class, despite experiencing equally low levels of support.ConclusionsThe results underscore the need to take youths’ orientation toward the peer context into account alongside support when tapping into the role of peers, because individuals with low levels of support and EPO functioned substantially better than individuals with similar low levels of support but high levels of EPO.

Aims: Insulin autoantibodies (IAA) are often the first marker of autoimmunity detected in children in the preclinical phase of type 1 diabetes (T1D). Currently, the vast majority of laboratories adopt the radiobinding micro-assay (RBA) for measuring IAA. Our aim was to replace RBA with a novel non-radioactive IAA Luciferase Immuno Precipitation System (LIPS) assay with improved performance. Methods: We developed (pro)insulin antigens with alternative placements of a NanoLuc™ luciferase reporter (NLuc). Performance in LIPS was evaluated by testing sera from new onset T1D (n = 80), blood donors (n = 123), schoolchildren (n = 186), first-degree relatives (FDRs) from the Bart’s Oxford family study (n = 53) and from the Belgian Diabetes Registry (n = 136), coded sera from the Islet Autoantibody Standardization Program (IASP) (T1D n = 50, blood donors n = 90). Results: IAA LIPS based on B chain-NLuc proinsulin or B chain-NLuc insulin, in which NLuc was fused at the C-terminus of the insulin B chain, required only 2 μL of serum and a short incubation time, showed high concordance with RBA (Spearman r = 0.866 and 0.833, respectively), high assay performance (B chain-NLuc proinsulin ROC-AUC = 0.894 and B chain-NLuc insulin ROC-AUC = 0.916), and an adjusted sensitivity at 95% specificity ranking on par with the best assays submitted to the two most recent IASP workshops. In FDRs, the IAA LIPS showed improved discrimination of progressors to T1D compared to RBA. Conclusions: We established a novel high-performance non-radioactive IAA LIPS that might replace the current gold standard RBA and find wide application in the study of the IAA response in T1D.

OBJECTIVE The increasing importance of peers in adolescence and emerging adulthood has been widely acknowledged. However, longitudinal research linking the peer context to diabetes management and outcomes is scarce. The present longitudinal study in a large sample of youths with type 1 diabetes related both positive and negative peer variables to diabetes outcomes over a time interval of 1 year. RESEARCH DESIGN AND METHODS Our sample consisted of 467 adolescents (14–17 years of age) and emerging adults (18–25 years of age) with type 1 diabetes who participated in a two-wave longitudinal study. Questionnaires tapped into peer support, extreme peer orientation, parental responsiveness, diabetes-related distress, and treatment adherence. HbA1c values were obtained from the treating physicians of patients. Cross-lagged analysis from a structural equation modeling approach was performed to assess the directionality of effects. RESULTS Peer support negatively predicted diabetes-related distress over time. Extreme peer orientation positively predicted treatment distress over time. Parental responsiveness negatively predicted food distress over time. Treatment adherence negatively predicted extreme peer orientation, treatment distress, and HbA1c values over time. For emerging adults specifically, there was a reciprocal relationship between HbA1c values and extreme peer orientation because they positively predicted each other. CONCLUSIONS This study highlights the importance of peers in predicting the functioning of youths with type 1 diabetes. Additionally, treatment adherence at baseline was found to negatively predict extreme peer orientation, treatment distress, and worse glycemic control over time. In sum, the current study underscores the importance of the peer context for adolescents and emerging adults with type 1 diabetes.

The present study investigated identity formation in adolescents and emerging adults with type 1 diabetes and its relation to psychological and diabetes-specific functioning. As diabetes management is especially challenging in these life periods, identity problems may not only hamper psychological adjustment, but could also impact diabetes management. A total of 431 patients were 1:1 matched with control participants, based on age, gender, and context (student, employed, other). To investigate identity types or statuses, cluster analysis on different identity processes was conducted, resulting in six statuses. Patients in foreclosure and achievement (both characterized by strong identity commitments) presented with the most adaptive functioning. Patients in troubled diffusion and moratorium (both characterized by a maladaptive type of exploration) showed the least adaptive scores on well-being, diabetes-specific problems, treatment adherence, and illness-perceptions. The present study underscores the importance of assessing identity issues in youth with type 1 diabetes. ispartof: PSYCHOLOGY HEALTH & MEDICINE vol:25 issue:5 pages:519-529 ispartof: location:England status: published

Youth with type 1 diabetes are confronted with the challenging task of integrating diabetes into their identity. This integration process, referred to as illness identity, may play an important role in how youth with type 1 diabetes cope with normative and illness-specific challenges. In line with socio-ecological theorizing, the present study investigated the longitudinal interplay between illness identity and two important social contexts for youth, the parent and peer contexts. A total of 559 (54.5% female; mean age = 18.8 years) adolescents (14–17 years) and emerging adults (18–25 years) with type 1 diabetes completed questionnaires at three time-points with intervals of one year. A total of 98% of these participants had the Belgian nationality, and all of them spoke Dutch. At each time point, illness identity (i.e., acceptance, enrichment, rejection, and engulfment), peer support, extreme peer orientation, parental responsiveness, parental psychological control, and parental overprotection were self-assessed. The present findings show that overprotective parenting may lead to youth feeling engulfed by their diabetes. Further, when type 1 diabetes becomes adaptively integrated into youth’s identity, the data suggest that youth may be better prepared to engage in healthy peer relationships. Thus, the present findings show that illness identity may be affected by the social context, and in turn may have an impact on parent and peer relationships as well. In general, the present findings underscore the importance of adaptive illness integration for youth with type 1 diabetes, and further emphasize the importance of achieving a coherent identity. ispartof: Journal Of Youth And Adolescence vol:49 issue:2 pages:449-466 ispartof: location:United States status: published

AIMS: A family approach was applied to examine youth, maternal, and paternal control perceptions in relation to type 1 diabetes outcomes in adolescents and emerging adults. Mean levels of personal and treatment control were compared among patients and parents. Their associations with diabetes outcomes were examined as well. METHODS: The sample included 330 patient-mother-father triads. Patients' (48% male) mean age was 18.25 years (SD = 2.98). All respondents reported on their control perceptions and youth treatment adherence. Physicians provided HbA1c-values. RESULTS: Paired-samples t-tests revealed higher personal control in patients compared to parents. Regression analyses examined if control perceptions predicted treatment adherence and HbA1c. Main effects for patient and maternal personal control and two-way interactions showed the best outcomes when both patients and mothers reported high personal control. Main effects of patient, maternal, and paternal treatment control and three-way interaction terms revealed better outcomes in case of high treatment control in patients and at least one parent, while the poorest outcomes were observed in case of low treatment control in all respondents. CONCLUSIONS: The findings highlight the importance of parental control perceptions on top of patients' own perceptions. A family perspective on illness perceptions and their associations with diabetes outcomes is encouraged. ispartof: DIABETES RESEARCH AND CLINICAL PRACTICE vol:150 pages:264-273 ispartof: location:Ireland status: published

OBJECTIVE Disturbed eating behavior (DEB) is prevalent in youth with type 1 diabetes and is accompanied by an increased risk for complications, morbidity, and mortality. Prospective studies on DEB in the challenging transition to adulthood are scarce. This longitudinal study examined DEB over a 1-year period and investigated the directionality of effects linking DEB to diabetes-specific functioning and depressive symptoms in adolescents and emerging adults. RESEARCH DESIGN AND METHODS Three hundred youth (16–28 years old) with type 1 diabetes participated in a two-wave longitudinal study. Questionnaires measured DEB (Diabetes Eating Problem Survey-Revised [DEPS-R]), self-management, diabetes distress, and depressive symptoms. HbA1c values were obtained from physicians. Mixed ANOVA and cross-lagged analysis were used to examine prospective changes and directionality of effects, respectively. RESULTS Mean DEB remained stable in the total sample, but significant individual differences were observed based on the cutoff score of the DEPS-R: 19% displayed persistent DEB and 8% increased and 7.3% decreased in DEB over time. The remaining individuals scored low on DEB over time. These four groups were differentiated based on insulin restriction, omission, diabetes-specific functioning, and depressive symptoms. Cross-lagged analyses indicated that DEB predicted relative increases in depressive symptoms over time, whereas reciprocal associations with glycemic control were found. CONCLUSIONS This longitudinal study highlights the substantial impact DEB may have in the transition to adulthood, with a substantial portion of youth with type 1 diabetes being at risk for clinical DEB. Prospective pathways linking DEB to functioning were found, emphasizing the clinical relevance of assessing DEB over time.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years.METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

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. ispartof: Psychology & Health vol:34 issue:4 pages:438-455 ispartof: location:England status: published

Purpose Although prior research has stressed the role of personality in adjusting to type 1 diabetes, longitudinal research is lacking. The objectives of the present study were twofold: (1) to chart the development of patients’ personality over a 2-year period; and (2) to examine prospective associations among personality, treatment adherence, glycemic control, and diabetes-specific distress. Methods Adolescents and emerging adults with type 1 diabetes, aged 14–25 years (Mage = 18.86 years, 54% female), participated in a three-wave longitudinal study spanning 2 years (n = 560 at Time 1). Patients filled out questionnaires on Big Five personality traits, treatment adherence, and diabetes-specific distress. HbA1c values were obtained from treating physicians. We used latent growth curve modeling to examine the development of patients’ personality. Cross-lagged path analysis was performed to examine prospective associations among the study variables. Results First, we observed mean-level increases in extraversion, agreeableness, and conscientiousness over the course of the study. Second, we uncovered bidirectional associations between personality and several important indicators of adjustment. Lower conscientiousness and higher extraversion predicted a relative decrease in treatment adherence 1 year later. Poorer treatment adherence, in turn, predicted relative decreases in conscientiousness and agreeableness over time. Furthermore, lower emotional stability predicted a relative increase in distress 1 year later. Higher distress, in turn, predicted a relative decrease in agreeableness over time. Finally, lower conscientiousness predicted poorer glycemic control 1 year later. Conclusions This study found young patients to move toward a more mature personality and stressed the importance of personality in adjusting to type 1 diabetes.

This study examined inter-individual differences in depressive symptom development in young adults with type 1 diabetes. Individuals with persistent depressive symptoms were at risk for suboptimal development in terms of illness perceptions, illness functioning, and self-esteem. Individuals reporting no/minimal depressive symptoms over time were characterized by the most optimal development. publisher: Elsevier articletitle: Change and stability in depressive symptoms in young adults with type 1 diabetes journaltitle: Diabetes Research and Clinical Practice articlelink: http://dx.doi.org/10.1016/j.diabres.2015.10.023 content_type: article copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved. ispartof: Diabetes Research and Clinical Practice vol:111 pages:93-96 ispartof: location:Ireland status: published

Objective. The principal aim of this study was to examine the longitudinal interplay of depressive symptoms, diabetes-specific perceptions and distress, and glycemic control in emerging adults with type 1 diabetes. Methods. Emerging adults with type 1 diabetes (18-30 years old) participated in a two-wave longitudinal study spanning five years (N=164 at Time 1). Patients completed questionnaires on depressive symptoms, diabetes-specific distress (treatment-related, food-related, emotional, and social support problems), and illness perceptions (consequences and personal control) at baseline and follow-up. HbA1c values were obtained from treating clinicians. We investigated the directionality of effects using cross-lagged path analysis. Results. Stronger perceptions of control predicted a relative decrease in treatment-related problems five years later, whereas stronger perceptions of consequences predicted a relative increase in depressive symptoms, treatment-related, food-related, emotional, and social support problems over time. Furthermore, higher depressive symptoms predicted a relative increase in social support problems five years later. None of the study variables were related to changes in glycemic control over time. Conclusions. Our findings stress the importance of addressing patients’ perceptions and beliefs about their diabetes. Clinicians should find a delicate balance between stressing the importance of diabetes care and preventing patients from feeling overwhelmed or engulfed by the burden of diabetes care. Furthermore, our findings advocate for depression screening and treatment as key elements in holistic diabetes care, given the relatively high prevalence of elevated depressive symptoms in this population. ispartof: Health Psychology vol:34 issue:11 pages:1058-1065 ispartof: location:United States status: published

Context: Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases. Evidence Acquisition: Systematic search of four databases (MEDLINE, Embase, Web of Science, and Cochrane Library) using the search terms "diabetes" or "ketoacidosis" and "pembrolizumab," "nivolumab," "PD-1 inhibitor," or "immunotherapy." Included were articles published in English between 1 January 2012 and 1 January 2018. The search was supplemented by bibliographic searches of the complete reference lists of all included papers. Evidence Synthesis: We provide an overview of all published cases (n = 42) of PD-1 inhibitor-induced type 1 diabetes mellitus to date, including a well-characterized case of islet cell antibody and glutamic acid decarboxylase antibody-positive diabetes mellitus, in a patient with a diabetes-prone HLA genotype. She presented with diabetic ketoacidosis during pembrolizumab therapy for a metastatic uveal melanoma. Furthermore, we discuss potential pathogenic mechanisms, clinical presentation, prognostic markers (beta-cell antibodies and HLA type), treatment, and a screening protocol. Conclusions: Because the use of immunotherapy will increase, it is essential that all clinicians are aware of diabetic ketoacidosis as a rare and life-threatening side effect of immunotherapy. Blood glucose monitoring during anti-PD-1 therapy is necessary.

We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes.A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity (Unlike

We examined whether measures of glycaemic variability (GV), assessed by continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG), can complement or replace measures of beta cell function and insulin action in detecting the progression of preclinical disease to type 1 diabetes. Twenty-two autoantibody-positive (autoAb+) first-degree relatives (FDRs) of patients with type 1 diabetes who were themselves at high 5-year risk (50%) for type 1 diabetes underwent CGM, a hyperglycaemic clamp test and OGTT, and were followed for up to 31 months. Clamp variables were used to estimate beta cell function (first-phase [AUC5–10 min] and second-phase [AUC120–150 min] C-peptide release) combined with insulin resistance (glucose disposal rate; M 120–150 min). Age-matched healthy volunteers (n = 20) and individuals with recent-onset type 1 diabetes (n = 9) served as control groups. In autoAb+ FDRs, M 120–150 min below the 10th percentile (P10) of controls achieved 86% diagnostic efficiency in discriminating between normoglycaemic FDRs and individuals with (impending) dysglycaemia. M 120–150 min outperformed AUC5–10 min and AUC120–150 min C-peptide below P10 of controls, which were only 59–68% effective. Among GV variables, CGM above the reference range was better at detecting (impending) dysglycaemia than elevated SMBG (77–82% vs 73% efficiency). Combined CGM measures were equally efficient as M 120–150 min (86%). Daytime GV variables were inversely correlated with clamp variables, and more strongly with M 120–150 min than with AUC5–10 min or AUC120–150 min C-peptide. CGM-derived GV and the glucose disposal rate, reflecting both insulin secretion and action, outperformed SMBG and first- or second-phase AUC C-peptide in identifying FDRs with (impending) dysglycaemia or diabetes. Our results indicate the feasibility of developing minimally invasive CGM-based criteria for close metabolic monitoring and as outcome measures in trials.

Context and Objective: In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb+) offspring and siblings of patients with type 1 diabetes (T1D). Design: The design is a registry-based study. Setting: Functional tests were performed in a hospital setting. Participants: Persistently autoAb+ first-degree relatives of patients with T1D (n = 81; age 5–39 years). Main Outcome Measures: We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC5–10min; min 5–10) was determined in all relatives and second-phase release (AUC120–150min; min 120–150) in those aged 12–39 years (n = 62). Results: Overall, the predictive ability of AUC5–10min was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80–0.98] vs 0.81 [0.70–0.93]). Fasting blood glucose (FBG) and AUC5–10min provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84–1.00]). In multivariate Cox regression analysis, AUC5–10min (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC5–10min below percentile 10 of controls was associated with 50–70% progression to T1D regardless of age. Similar results were obtained for AUC120–150min. Conclusions: Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb+ offspring and siblings of T1D patients to predict impending diabetes.

OBJECTIVE Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose. RESEARCH DESIGN AND METHODS In the included patients (n = 40 otelixizumab, n = 40 placebo), β-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay. RESULTS At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of β-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA+ participants with relatively preserved β-cell function [≥25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome. CONCLUSIONS There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional β-cell mass and presence of IAA as inclusion criteria.

[This corrects the article DOI: 10.1371/journal.pone.0166702.].

OBJECTIVE We investigated whether islet autoantibody profile, HLA-DQ genotype, and age influenced a 20-year progression to diabetes from first autoantibody positivity (autoAb+) in first-degree relatives of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Persistently islet autoAb+ siblings and offspring (n = 462) under 40 years of age were followed by the Belgian Diabetes Registry. AutoAbs against insulin (IAA), GAD (GADA), IA-2 antigen (IA-2A), and zinc transporter 8 (ZnT8A) were determined by radiobinding assay. RESULTS The 20-year progression rate of multiple-autoAb+ relatives (n = 194) was higher than that for single-autoAb+ participants (n = 268) (88% vs. 54%; P < 0.001). Relatives positive for IAA and GADA (n = 54) progressed more slowly than double-autoAb+ individuals carrying IA-2A and/or ZnT8A (n = 38; P = 0.001). In multiple-autoAb+ relatives, Cox regression analysis identified the presence of IA-2A or ZnT8A as the only independent predictors of more rapid progression to diabetes (P < 0.001); in single-autoAb+ relatives, it identified younger age (P < 0.001), HLA-DQ2/DQ8 genotype (P < 0.001), and IAA (P = 0.028) as independent predictors of seroconversion to multiple positivity for autoAbs. In time-dependent Cox regression, younger age (P = 0.042), HLA-DQ2/DQ8 genotype (P = 0.009), and the development of additional autoAbs (P = 0.012) were associated with more rapid progression to diabetes. CONCLUSIONS In single-autoAb+ relatives, the time to multiple-autoAb positivity increases with age and the absence of IAA and HLA-DQ2/DQ8 genotype. The majority of multiple-autoAb+ individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, HLA-DQ genotype, and number of autoAbs. These data may help to refine the risk stratification of presymptomatic type 1 diabetes.

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteor ...

The present study assessed the centrality of one's illness self-concept, or the degree to which chronic illness intrudes upon one's self, in a sample of 478 18-35-year-old patients with Type 1 diabetes. Confirmatory factor analysis indicated that illness self-concept centrality was a one-dimensional construct, despite the fact that three constituting components (i.e. pervasiveness, directionality, and illness self-consciousness) have been forwarded. Further, important demographic and clinical correlates of illness self-concept were identified: women, unemployed individuals, individuals with a lower educational level, and patients with an insulin pump had a more central illness self-concept. Finally, a series of correlation and regression analyses indicated that, despite the fact that illness self-concept centrality was negatively related to emotional stability, self-esteem, and diabetes integration, and positively to perceived consequences of diabetes, illness self-concept had unique predictive value over and above these variables for problem areas in diabetes and depressive symptoms. Implications and suggestions for future research are outlined.

We investigated the prevalence of diabetes autoantibodies (Abs) in Cameroonian patients and controls, assessed their contribution in disease classification and compared results with data from Belgium.Abs against GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302 recently diagnosed Cameroonian patients with diabetes and 184 control subjects without diabetes aged below 40 years.Only 27 (9%) Cameroonian patients were younger than 15 years. Overall, 29% of patients presented at least one diabetes-associated antibody vs 9% in healthy controls (24% vs 7% for GADA (p0.001), 10% vs 3% for IA-2A (p0.006), 4% vs 2% for ZnT8A). Ab(+) patients had lower C-peptide levels (p0.001), were more often insulin-treated (p0.002) and were as frequently diagnosed with type 1 diabetes as Ab(-) patients. Only 43% of Ab(+) patients aged 15-39 years were clinically classified as having type 1 diabetes in Cameroon vs 96% in Belgium (p0.001). Not one Ab(+) Cameroonian patient carried HLA-DQ2/DQ8 genotype vs 23% of Belgian Ab(+) patients (p0.001). Younger age at diagnosis and antibody positivity were independent predictors of insulin therapy. Ab(+) Cameroonian patients were older (p0.001), had higher BMI (p0.001) and lower Ab titers than Belgian Ab(+) patients. In ketonuric patients, prevalence of autoantibodies was similar as in non-ketonuric patients.In Cameroonian patients with diabetes aged under 40 years, antibody-positivity is not clearly related to disease phenotype, but may help predict the need for insulin treatment.

Autoimmune disease results from a loss of tolerance to self-antigens in genetically susceptible individuals. Completely understanding this process requires that targeted antigens be identified, and so a number of techniques have been developed to determine immune receptor specificities. We previously reported the construction of a phage-displayed synthetic human peptidome and a proof-of-principle analysis of antibodies from three patients with neurological autoimmunity. Here we present data from a large-scale screen of 298 independent antibody repertoires, including those from 73 healthy sera, using phage immunoprecipitation sequencing. The resulting database of peptide-antibody interactions characterizes each individual’s unique autoantibody fingerprint, and includes specificities found to occur frequently in the general population as well as those associated with disease. Screening type 1 diabetes (T1D) patients revealed a prematurely polyautoreactive phenotype compared with their matched controls. A collection of cerebrospinal fluids and sera from 63 multiple sclerosis patients uncovered novel, as well as previously reported antibody-peptide interactions. Finally, a screen of synovial fluids and sera from 64 rheumatoid arthritis patients revealed novel disease-associated antibody specificities that were independent of seropositivity status. This work demonstrates the utility of performing PhIP-Seq screens on large numbers of individuals and is another step toward defining the full complement of autoimmunoreactivities in health and disease.

We investigated whether islet autoantibody profile,Persistently islet autoAbThe 20-year progression rate of multiple-autoAbIn single-autoAb

Objectives: We evaluated the Bio-Rad (Irvine, CA) D-100 and the Sebia (Lisses, France) Capillarys 3 Tera for the measurement of hemoglobin A1c (HbA1c) in venous blood samples. Methods: Whole-blood samples and control material were analyzed with the D-100 and Capillarys 3 Tera and compared with our routine method, HLC-723G7 (Tosoh, Tokyo, Japan). An evaluation protocol to test precision, trueness, linearity, carryover, and selectivity was set up according to Clinical and Laboratory Standards Institute guidelines. The results were presented in National Glycohemoglobin Standardization Program and International Federation of Clinical Chemistry (IFCC) units. Results: Both systems showed excellent precision (total coefficients of variation

Objective To examine the role of diabetes-specific parental regulation and general parenting dimensions (responsiveness and psychological control) in treatment adherence throughout adolescence and emerging adulthood. Methods A total of 521 patients (aged 14-25 years) with Type 1 diabetes, 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.

This long-term prospective study examined whether illness self-concept (or the degree to which chronic illness becomes integrated in the self) mediated the pathway from self-esteem to problem areas in diabetes in emerging adults with Type 1 diabetes. Having a central illness self-concept (i.e. feeling overwhelmed by diabetes) was found to relate to lower self-esteem, and more treatment, food, emotional, and social support problems. Furthermore, path analyses indicated that self-esteem was negatively related to both levels and relative changes in these problem areas in diabetes over a period of 5 years. Illness self-concept fully mediated these associations.

Objective. The present study, which is part of a larger longitudinal study focusing on the biopsychosocial functioning of emerging adults with type 1 diabetes, examined how perceived personal control, coping, and HbA1c relate to one another over time. Design and main outcome measures. Emerging adults with type 1 diabetes (18-30 years old) participated in a two-wave longitudinal study spanning five years (N=164 at Time 1). At both times, patients completed questionnaires on perceived control and coping (i.e., diabetes integration, avoidant coping, and passive resignation). HbA1c values were obtained from treating clinicians. We investigated the directionality of effects using cross-lagged path analysis. Results. Higher HbA1c values predicted relative decreases in diabetes integration and increases in avoidant coping five years later. Feeling less in control over diabetes predicted the use of passive coping over time. Passive coping predicted a relative decrease in perceived control five years later. Conclusion. These findings indicate that tackling poor glycaemic control is not only important to avoid medical complications but also to prevent patients from resorting to more avoidant coping strategies. Furthermore, given the longitudinal interplay between perceived control and passive coping, it is important that intervention efforts include both cognitive and behavioral components to be effective. peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=gpsh20 ispartof: Psychology & Health vol:31 issue:5 pages:622-635 ispartof: location:England status: published

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 (AutoDelfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive first-degree 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 (r2 = 0.96-0.99; P

OBJECTIVE The current study examined the utility of a new self-report questionnaire, the Illness Identity Questionnaire (IIQ), which assesses the concept of illness identity, or the degree to which type 1 diabetes is integrated into one’s identity. Four illness identity dimensions (engulfment, rejection, acceptance, and enrichment) were validated in adolescents and emerging adults with type 1 diabetes. Associations with psychological and diabetes-specific functioning were assessed. RESEARCH DESIGN AND METHODS A sample of 575 adolescents and emerging adults (14–25 years of age) with type 1 diabetes completed questionnaires on illness identity, psychological functioning, diabetes-related problems, and treatment adherence. Physicians were contacted to collect HbA1c values from patients’ medical records. Confirmatory factor analysis (CFA) was conducted to validate the IIQ. Path analysis with structural equation modeling was used to examine associations between illness identity and psychological and diabetes-specific functioning. RESULTS CFA indicated that the IIQ has a clear factor structure, meaningfully differentiating four illness identity dimensions. Rejection was related to worse treatment adherence and higher HbA1c values. Engulfment was related to less adaptive psychological functioning and more diabetes-related problems. Acceptance was related to more adaptive psychological functioning, fewer diabetes-related problems, and better treatment adherence. Enrichment was related to more adaptive psychological functioning. CONCLUSIONS The present findings underscore the importance of the concept of illness identity. A valid and reliable measure, the IIQ, is introduced to measure four illness identity dimensions in individuals with type 1 diabetes. These four illness identity dimensions were uniquely related to psychological and diabetes-specific functioning.

OBJECTIVE This study assesses β-cell replication in human donor organs and examines possible influences of the preterminal clinical conditions. RESEARCH DESIGN AND METHODS β-Cell replication was quantified in a consecutive series of n = 363 human organ donors using double immunohistochemistry for Ki67 and insulin. Uni- and multivariate analysis was used to correlate replication levels to clinical donor characteristics and histopathologic findings. RESULTS β-Cell replication was virtually absent in most donors, with ≤0.1% Ki67-positive β-cells in 72% of donors. A subpopulation of donors, however, showed markedly elevated levels of replication of up to 7.0% Ki67-positive β-cells. β-Cell replication was accompanied by the increased replication of glucagon-, somatostatin-, and CA19.9-positive cells. Prolonged life support, kidney dysfunction, relatively young donor age, inflammatory infiltration, and prolonged brain death before organ retrieval were all found to be significantly associated with an increased level (≥90th percentile) of β-cell replication, with the first three risk factors being independent predictors. Increased β-cell replication was most often noted in relatively young donors (≤25 years) who received prolonged (≥3 days) life support (68%); in contrast, it was rare in donors with a short duration of life support regardless of age (1%). Prolonged life support was accompanied by increased levels of CD68+ and LCA/CD45+ infiltration in the pancreatic parenchyma. CONCLUSION These results indicate that preterminal clinical conditions in (young) organ donors can lead to increased inflammatory infiltration of the pancreas and to increased β-cell replication.