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Objective: Standardised person‐reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and unsuccessful at international level. We aimed to address this by developing a person‐centred outcome set for Type 1 and Type 2 diabetes, using a methodology with prospects for increased implementability and sustainability in international health settings. Methods: We used a three‐round questionnaire‐based Delphi study to reach consensus on the outcome set. We invited key stakeholders from 19 countries via purposive snowball sampling, namely people with diabetes (N = 94), healthcare professionals (N = 65), industry (N = 22) and health authorities (N = 3), to vote on the relevance and measurement frequency of 64 previously identified clinical and person‐reported outcomes. Subsequent consensus meetings concluded the study. Results: The list of preliminary outcomes was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: (1) linked to a medical visit (e.g. diabetes‐specific well‐being, symptoms and psychological health) and (2) annually (e.g. clinical data, general well‐being and diabetes self management‐related outcomes). Conclusions: PROs are often considered in a non‐standardised way in routine diabetes care. We propose a person‐centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised collection of meaningful outcomes at scale, supporting individual and population level healthcare decision making. It will be implemented and tested in Europe as part of the H2O project. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: This study aims to evaluate the stability of C‐peptide over time and to compare fasting C‐peptide and C‐peptide response after mixed‐meal tolerance test (MMTT) at T90 or T120 with C‐peptide area under the curve (AUC) in long‐standing type 1 diabetes. Methods: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C‐peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30‐T60‐T90‐T120, 30–120 min after ingestion of mixed‐meal) (n = 168). Fasting C‐peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C‐peptide secretion and the correspondence of C‐peptide at MMTT T90 / T120 and total AUC were assessed. Results: A total of 153 participants (25%) had detectable fasting serum C‐peptide (i.e ≥ 3.8 pmol/L). Fasting C‐peptide was significantly lower at Year 1 (p < 0.001, effect size = −0.16). Participants with higher fasting C‐peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non‐detectable fasting and post‐meal serum C‐peptide concentrations. The T90 and T120 C‐peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C‐peptide was only detectable at MMTT and not in the fasting state. Conclusions: Stimulated C‐peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C‐peptide at 1‐year follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production in-vitro, providing an appealing immunotherapy to intervene in autoimmune disease progression. Methods: A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry. Results: The tolDC vaccine induced a profound and durable decline in preexisting autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS+CCR4+TIGIT+ Tregs and CD103+ tissue-resident and CCR6+ effector memory CD4+ T-cells increased in response to the first tolDC injection, the latter declining thereafter below baseline levels. Discussion: Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D. [ABSTRACT FROM AUTHOR]

Aim: Automated insulin delivery systems have improved glycaemic control in people with type 1 diabetes mellitus. The analysis investigated predictors of improved sensor glucose time‐in‐range (TIR; 70‐180 mg/dl) based on real‐world use of the MiniMed 780G advanced hybrid closed‐loop (AHCL) system. Methods: Data uploaded by MiniMed 780G system users from August 2020‐July 2021 were analysed using univariate and multivariable models to identify baseline, demographic and system use characteristics associated with TIR after AHCL initiation (post‐AHCL). System settings associated with improved TIR post‐AHCL were identified and their impact on time below range (TBR, <70 mg/dl) post‐AHCL was explored. Results: In total, 12 870 users were included, of which 2977 had baseline sensor glucose data. Baseline TIR and time in AHCL (defined as the percentage of time the system was in Auto‐mode) were positively associated with TIR post‐AHCL with larger values predicting greater mean TIR post‐AHCL. Characteristics inversely associated with TIR post‐AHCL included the percentage of daily basal insulin dose, daily autocorrection dose, number of daily AHCL exits triggered by the system and number of daily alarms, wherein larger values of these characteristics predicted lower mean TIR post‐AHCL. System settings that predicted the largest mean TIR post‐AHCL were active insulin time of 2 h and glucose target of 100 mg/dl. Active insulin time was not associated with TBR post‐AHCL. Conclusion: Modifiable factors, including optimized pump settings, can allow users to achieve glycaemic targets with >80% TIR. The findings from this analysis will potentially guide the optimal use of the MiniMed 780G system and facilitate meaningful improvements in safe glycaemic control. [ABSTRACT FROM AUTHOR]

Background Not much is known about the effects of glycemic variability (GV) during the pre- and periconception period on pregnancy/perinatal complications. GV could potentially contribute to identification of high-risk pregnancies in women with type 1 diabetes. Methods An explorative retrospective cohort study was conducted between January 2014 and May 2019. Glucose data were retrieved from electronic patient charts. Pre-/periconceptional GV and GV during all three trimesters was expressed as mean glucose, standard deviation (SD), Coefficient of Variation (CV), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI) and Average Daily Risk Range (ADRR). Maternal and neonatal complications were summarized using a composite total complication score. Binary logistic regression analyses were conducted to assess associations between the GV measures and a total complication score>3, a maternal complication score>1 and a neonatal complication score>1. Results Of 63 eligible women, 29 women (38 pregnancies) were included. Women in the group with a total complication score>3 had a significantly higher ADRR at conception (OR 1.1, CI 1.0–1.2, p=0.048). No statistically significant correlations between complication score and any other GV metric besides the ADRR were found. Although not significant, in the group with a complication score>3, odds ratios>1 were found for SD in trimester 1 (OR 1.6, CI 0.6–4.5, p=0.357) and trimester 2 (OR 1.8, CI 0.5–6.2, p=0.376). Conclusions Presence of a positive association between GV and pregnancy and perinatal complications depends on which pregnancy period is assessed and the GV metrics that are used. [ABSTRACT FROM AUTHOR]

Introduction: C‐peptide is an important marker to assess residual insulin production in individuals with type 1 diabetes (T1D). The accuracy and detection limits of C‐peptide assays are important to detect C‐peptide microsecretion and to reliably observe changes over time in these people. We compared and verified two commercially available assays able to measure C‐peptide in the picomolar range. Methods: The ultrasensitive Mercodia enzyme‐linked immunosorbent C‐peptide assay (ELISA) was compared with the Beckman immunoradiometric assay (IRMA) for C‐peptide, assessing reproducibility (coefficient of variation [CV]), limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ). Results: For both assays within‐run and between‐run variation were high at the low (around the detection limit) C‐peptide concentration range, with CVs of around 40%. LoB values for the ultrasensitive ELISA and the IRMA were 1.3 and 0.16 pmol/L respectively. LoD values were 2.4 and 0.54 pmol/L respectively. LoQ values were 9.7 and 3.8 pmol/L respectively. Only the IRMA met the specifications claimed by the manufacturer. Conclusions: The IRMA provided the lowest threshold for quantification of serum C‐peptide. LoQ of commercially available assays should be established in‐house before applying them in research studies and clinical trials in which low C‐peptide levels have clinical or scientific relevance. [ABSTRACT FROM AUTHOR]

Aims: To examine whether frequency, perceived severity and fear of hypoglycaemia are independently associated with diabetes‐specific quality of life in adolescents with type 1 diabetes. Methods: Cross‐sectional self‐reported data on demographics, frequency and perceived severity of both self‐treated and severe hypoglycaemia, fear of hypoglycaemia (Hypoglycaemia Fear Survey—Child version) and diabetes‐specific quality of life (Pediatric Quality of Life Diabetes Module; PedsQL‐DM) were obtained from the project 'Whose diabetes is it anyway?'. Hierarchical regression analyses were performed for the total scale and recommended summary scores of the PedsQL‐DM as dependent variables; independent variables were entered in the following steps: (1) age, gender and HbA1c, (2) frequency of hypoglycaemia, (3) perceived severity of hypoglycaemia and (4) fear of hypoglycaemia. Results: Adolescents (12–18 years; n = 96) completed questionnaires. In the first three steps, female gender (p < 0.05), higher HbA1c (p < 0.05), higher frequency of severe hypoglycaemia (p < 0.05) and higher perceived severity of severe (p < 0.05) and self‐treated hypoglycaemia (p < 0.001) were significantly associated with lower diabetes‐specific quality of life (β ranging from 0.20 to 0.35). However, in the final model only fear of hypoglycaemia was significantly associated with QoL (p < 0.001). Adolescents with greater fear reported lower diabetes‐specific quality of life, with 52% explained variance. This pattern was observed across subdomains of diabetes‐specific quality of life. Conclusions: Fear of hypoglycaemia was the only factor independently associated with diabetes‐specific quality of life, whereas frequency and perceived severity of hypoglycaemia were not. These findings highlight the importance of awareness and assessment of fear of hypoglycaemia in clinical practice. [ABSTRACT FROM AUTHOR]

Aim To assess 1) the prevalence of children and adolescents with type 1 diabetes (T1D) changing from low-risk into borderline-high-risk lipid levels or from borderline-high-risk into high-risk lipid levels ('lose track of lipids') and 2) the power of a risk score including the determinants HbA1c, body mass index (BMI), gender, age, diabetes duration and ethnicity in predicting which patients lose track of lipids. Methods 651 children and adolescents with T1D were included in this longitudinal retrospective cohort study. Lipid dynamics and the impact of the risk score on losing track of lipids were evaluated. Kaplan-Meier analysis was used to estimate screening intervals. Results 31–43% percent of the patients had lost track of one or more lipids at the next lipid measurement. This happened more frequently in patients with a low-risk lipid level at start. Depending on the lipid parameter, 5% of patients with low-risk lipid levels lost track of lipids after 13–23 months. The risk score based on concomitant information on the determinants was moderately able to predict which patients would lose track of lipids on the short term. Conclusions A considerable number of children and adolescents with T1D loses track of lipids and does so within a 2-year screening interval. The predictive power of a risk score including age, BMI, gender, HbA1c, diabetes duration and ethnicity is only moderate. Future research should focus on another approach to the determinants used in this study or other determinants predictive of losing track of lipids on the short term. [ABSTRACT FROM AUTHOR]

Objectives: We aim to determine the prevalence and the course of anxiety and mood disorders in Dutch adolescents (12–18 years old) with type 1 diabetes, and to examine correlates of symptom severity, including parental emotional distress. Methods: Participants were 171 adolescents and 149 parents. The Diagnostic Interview Schedule for Children‐IV was used to assess current, past year and lifetime anxiety and mood disorders in adolescents. Symptom severity and diabetes distress were measured with validated questionnaires. Correlates of these symptoms were examined using hierarchical regression analyses and included demographics (adolescent sex and age), clinical factors (diabetes duration, treatment modality, most recent glycated hemoglobin A1c; all extracted from medical charts), adolescent diabetes distress, and parent emotional distress. Results: Twenty‐four (14%) adolescents met the criteria for ≥1 disorder(s) in the previous 12 months. Anxiety disorders were more prevalent than mood disorders (13% vs. 4%). Lifetime prevalence of anxiety and mood disorders was 29% (n = 49). The presence of any of these disorders earlier in life (from 5 years old up to 12 months prior to assessment) was associated with disorders in the past 12 months (OR = 4.88, p = 0.001). Higher adolescent diabetes distress was related to higher symptoms of anxiety (b = 0.07, p = 0.001) and depression (b = 0.13, p = 0.001), while demographics, clinical characteristics, and parental emotional distress were not related. Conclusions: Anxiety and mood disorders are common among adolescents and related to earlier disorders. Higher diabetes distress was related to higher symptom severity. Clinicians are advised to address past psychological problems and remain vigilant of these problems. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Advanced Nursing (John Wiley & Sons, Inc.) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims/hypothesis: Heterogeneity in individuals with type 1 diabetes has become more generally appreciated, but has not yet been extensively and systematically characterised. Here, we aimed to characterise type 1 diabetes heterogeneity by creating immunological, genetic and clinical profiles for individuals with juvenile-onset type 1 diabetes in a cross-sectional study. Methods: Participants were HLA-genotyped to determine HLA-DR-DQ risk, and SNP-genotyped to generate a non-HLA genetic risk score (GRS) based on 93 type 1 diabetes-associated SNP variants outside the MHC region. Islet autoimmunity was assessed as T cell proliferation upon stimulation with the beta cell antigens GAD65, islet antigen-2 (IA-2), preproinsulin (PPI) and defective ribosomal product of the insulin gene (INS-DRIP). Clinical parameters were collected retrospectively. Results: Of 80 individuals, 67 had proliferation responses to one or more islet antigens, with vast differences in the extent of proliferation. Based on the multitude and amplitude of the proliferation responses, individuals were clustered into non-, intermediate and high responders. High responders could not be characterised entirely by enrichment for the highest risk HLA-DR3-DQ2/DR4-DQ8 genotype. However, high responders did have a significantly higher non-HLA GRS. Clinically, high T cell responses to beta cell antigens did not reflect in worsened glycaemic control, increased complications, development of associated autoimmunity or younger age at disease onset. The number of beta cell antigens that an individual responded to increased with disease duration, pointing to chronic islet autoimmunity and epitope spreading. Conclusions/interpretation: Collectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is a chronic metabolic condition requiring intensive daily self-care to avoid both high and low blood glucose levels. Self-care and glycemic outcomes are particularly problematic in adolescence, a period known for its increased risk of emotional problems. However, the true scope of mood and anxiety disorders in adolescents with T1D is unknown. Earlier studies are limited by a small sample size, lack of diagnostic interview data, a focus on depression only, non-adolescent specific estimates, lack of information about parental emotional problems and/or a cross-sectional design. Diabetes LEAP is a two-year prospective observational cohort study examining (a) the prevalence and course of depression and anxiety in adolescents with T1D and their parents/caregivers, (b) the risk factors predicting the presence of these emotional problems, (c) their longitudinal relation with diabetes outcomes, and (d) the psychosocial care currently in place.Methods: Adolescents (12-18 years) from 8 Dutch pediatric diabetes clinics are interviewed using the DISC-IV to establish the presence of mood and anxiety disorders in the previous 4 weeks, the previous 12 months, and lifetime. They also complete questionnaires, including CDI-2, GAD-7, and PAID-T. Parents/caregivers complete PHQ-9, GAD-7, and PAID-PR. Follow-up assessments take place after 1 and 2 years.Discussion: This longitudinal study with diagnostic interviews in a large cohort of adolescents with T1D in the Netherlands will provide much needed information regarding the prevalence and course of depression and anxiety in this group, thereby opening avenues for proper recognition, prevention and timely treatment. [ABSTRACT FROM AUTHOR]

In this issue of Diabetologia, Alavi and Werner (10.1007/s00125-018-4676-1) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as ‘futile’. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a ‘futile’ effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality. [ABSTRACT FROM AUTHOR]

Objective: The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes. Research Design and Methods: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. Results: Totally 1113 (53% male) children (mean age 8.0 ± 2.1 years) from 18 centers in 17 countries, along with parents and 113 health‐care professionals, participated. There were substantial differences in mean HbA1c between centers ranging from 7.3 ± 0.8% (53 mmol/mol ± 8.7) to 8.9 ± 1.1% (74 mmol/mol ± 12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health‐care professionals that reported lower targets and more frequent testing, and (3) teams with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. Conclusions: The diabetes care teams’ cohesiveness and perspectives on treatment targets, expectations, and recommendations have an influence on parental targets, contributing to the differences in pediatric diabetes center outcomes. [ABSTRACT FROM AUTHOR]

Background: Few diabetes‐specific quality of life (QOL) tools are available for young children. Objectives: To design and evaluate, a new age‐specific QOL questionnaire and its associations with treatment regimens and metabolic control. Methods: Clinical, demographic data and centrally analyzed HbA1c were collected on 1133 children <11 years (girls 48%; mean ± SD age 8.0 ± 2.1 years; diabetes duration ≥1 year) from 18 centers (Europe, Japan, North America and Australia). Children completed the 10‐item Smiley Faces QOL questionnaire constructed for the study, and children ≥7 years also completed the KIDSCREEN‐10 Index. Results: In total, 1035 children completed the new Smiley Faces questionnaire which was well understood by 993 (70% ≥4 years and 96% ≥5 years, respectively). Internal consistency and reliability were good (Cronbach's α = .73). Inter‐item correlation ranged r = 0.047 to 0.451 indicating each item measures separate aspects of children's satisfaction construct. Convergent validity assessed by comparison to the HrQOL KIDSCREEN‐10 Index showed moderate correlation coefficient 0.501. Factor analysis revealed 3 factors explaining 51% of the variance. Children reported good QOL with most items positive, mean values between 1 and 2 on a 5‐point scale (lower scores indicating greater QOL). Diabetes satisfaction was unrelated to age, diabetes duration, HbA1c, or severe hypoglycemia. Girls were more satisfied than boys. Children on intensive regimens reported better QOL (P < .02). Main dissatisfaction related to insulin injections and blood sugar testing. Conclusions: The Smiley Faces questionnaire enables QOL assessment in young children and identification of areas of dissatisfaction and other clinically relevant items relating to diabetes management. [ABSTRACT FROM AUTHOR]

Objective. To evaluate (1) the longitudinal relationship between parental well-being and glycemic control in youth with type 1 diabetes and (2) if youth’s problem behavior, diabetes parenting behavior, and parental diabetes-distress influence this relationship. Research Design and Methods. Parents of youth 8–15 yrs (at baseline) (N=174) participating in the DINO study completed questionnaires at three time waves (1 yr interval). Using generalized estimating equations, the relationship between parental well-being (WHO-5) and youth’s HbA1c was examined. Second, relationships between WHO-5, Strength and Difficulties Questionnaire (SDQ), Diabetes Family Behavior Checklist (DFBC), Problem Areas In Diabetes-Parent Revised (PAID-Pr) scores, and HbA1c were analyzed. Results. Low well-being was reported by 32% of parents. No relationship was found between parents’ WHO-5 scores and youth’s HbA1c (β=−0.052, p=0.650). WHO-5 related to SDQ (β=−0.219, p<0.01), DFBC unsupportive scale (β=−0.174, p<0.01), and PAID-Pr (β=−0.666, p<0.01). Both DFBC scales (supportive β=−0.259, p=0.01; unsupportive β=0.383, p=0.017), PAID-Pr (β=0.276, p<0.01), and SDQ (β=0.424, p<0.01) related to HbA1c. Conclusions. Over time, reduced parental well-being relates to increased problem behavior in youth, unsupportive parenting, and parental distress, which negatively associate with HbA1c. More unsupportive diabetes parenting and distress relate to youth’s problem behavior. [ABSTRACT FROM AUTHOR]

Background Adolescents with type 1 diabetes are at an increased risk of disturbed eating behaviors ( DEBs). Objective The aims of this study are to (i) explore the prevalence of DEBs and associated 'yellow flags', and (ii) establish concordance between adolescents-parents and adolescents-clinicians with respect to DEBs. Methods Adolescents (11-16 yr) and parents completed questionnaires. A stepwise approach was used to assess DEBs: only adolescents whose answers raised psychological yellow flags for DEBs completed the Diabetes Eating Problems Scale - Revised and questions from the AHEAD study. Parents and clinicians shared their observations regarding possible DEBs. Kruskal-Wallis tests, post hoc Mann-Whitney U test, and chi-squared tests were utilized to examine clinical yellow flags. Cohen's kappa was used to assess concordance. Results Of 103 adolescents participated (51.5% girls), answers of 47 (46.5%) raised psychological yellow flags, indicating body and weight concerns. A total of 8% scored above cut-off for DEBs. Clinical yellow flags were elevated glycated hemoglobin A1c (p = 0.004), older age (p = 0.034), dieting frequency (p = 0.001), reduced quality of life (p = 0.007), less diabetes self-confidence (p = 0.015), worsened diabetes management (p < 0.001), and body dissatisfaction (p < 0.001). Body Mass Index (BMI) z-scores and gender were no yellow flags. Concordance between parents and adolescents was slight (k = 0.126 and 0.141), and clinicians and adolescents was fair (k = 0.332). Discussion Half of the adolescents reported body and weight concerns, less than 1 in 10 reported DEBs. Screening for yellow flags for DEBs as a part of clinical routine using a stepwise approach and early assistance is recommended to prevent onset or deterioration of DEBs. [ABSTRACT FROM AUTHOR]

Background: Early identification of children and adolescents with type 1 diabetes at high risk for development of complications is important, as early intervention may prevent further deterioration. Here we investigate the applicability of assessing skin advanced glycation end products (sAGEs) by skin autofluorescence (SAF) as a potential surrogate risk marker. Methods: This study included a cross-sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118 healthy controls across age categories (11-12, 13-14, 15-16, and 17-19 years old). In patients, the impact of current and historical glycated hemoglobin (HbA1c) values, age, and duration of diabetes on SAF was studied in a retrospective cohort study and analyzed with multivariable analyses. Results: SAF was significantly and similarly higher in patients when compared with controls across all age categories (P ≤ 0.009). For patients, age, duration of diabetes, and current and historical HbA1c were associated with P SAF in univariate analysis. Multivariate analysis showed no association between HbA1c and SAF. A subgroup of patients with a HbA1c-within-target (≤7.5 %/59 mmol/mol) were observed to have high SAF. Conclusion: Children and adolescents with type 1 diabetes show higher SAF than controls. The presumed correlation of high HbA1c with high SAF does not exist in all patients. Thus, use of this non-invasive measure may provide a surrogate marker for diabetic complications, additional to HbA1c. [ABSTRACT FROM AUTHOR]

Unlabelled: To test whether parenting stress and the quality of parent-child interaction were associated with glycemic control and quality of life (QoL) in young children (0-7 years) with type 1 diabetes (T1DM), we videotaped 77 families with a young child with T1DM during mealtime (including glucose monitoring and insulin administration). Parent-child interactions were scored with a specifically designed instrument. Questionnaires assessed general and disease-related parenting stress and (diabetes-specific (DS)) QoL. HbA(1c) (glycemic control) was extracted from the medical records. Both general and disease-related parenting stress were associated with a lower (DS)QoL (r ranged from -0.39 to -0.70, p < 0.05), but not with HbA(1c) levels. Furthermore, with regard to the parent-child interaction, emotional involvement of parents (r = 0.23, p < 0.05) and expressed discomfort of the child (r = 0.23, p < 0.05) were related to suboptimal HbA(1c) levels. There was no clear pattern in the correlations between parent-child interaction and (DS)QoL.Conclusion: The results support the notion that diabetes does not only affect the child with T1DM: T1DM is a family disease, as parenting factors (like stress and parent-child interactions) are associated with important child outcomes. Therefore, it is important for health-care providers to not only focus on the child with T1DM, but also on the family system. [ABSTRACT FROM AUTHOR]

BACKGROUND: Musculotendinous overuse injuries are prevalent in people with type 2 diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening may play a role. In this case-control study we determined whether patients with diabetes had poorer ultrasonographic structure in their Achilles tendons compared to age-matched controls. METHODS: People with type 1 diabetes or type 2 diabetes, and age-matched controls, had computerised ultrasound tissue characterisation of both Achilles tendons. In contiguous ultrasonographic images of the tendon, echopatterns were quantified and categorised into four echo-types. Tendon abnormality was quantified as sum of echo-types III+IV. Furthermore, skin autofluorescence (AF) of the forearm (AF-value) was gathered. RESULTS: Twenty four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20 controls were included. AF-value was higher in type 1 diabetes (1.55±0.17) than in their controls (1.39±0.18, p<0.001) and in type 2 diabetes (2.28±0.38) compared to their controls (1.84±0.32, p<0.001) Achilles tendons of type 2 diabetes patients contained more echo-types III+IV (14.1±7.9%) than matched controls (8.0±5.4%, p<0.001). There was a trend towards a difference in echo-types III+IV between type 1 diabetes patients (9.5±5.3%) and their controls (6.5±3.7%, p=0.055). In a stepwise linear regression analysis, body mass index (BMI) was moderately associated with tendon abnormality in patients with diabetes and controls ([beta]=0.393, p<0.001). CONCLUSIONS: Type 2, and possibly type 1, diabetes patients showed poorer ultrasonographic Achilles tendon structure that may be a risk factor for tendinopathy. Although markers for accumulation of advanced glycation end products were elevated in both diabetes populations, only BMI was associated with these abnormalities. TRIAL REGISTRATION NUMBER: NTR2209. [ABSTRACT FROM AUTHOR]

Background Musculotendinous overuse injuries are prevalent in people with type 2 diabetes. Non-enzymatic glycosylation of collagen resulting in tendon stiffening may play a role. In this case-control study we determined whether patients with diabetes had poorer ultrasonographic structure in their Achilles tendons compared to age-matched controls. Methods People with type 1 diabetes or type 2 diabetes, and age-matched controls, had computerised ultrasound tissue characterisation of both Achilles tendons. In contiguous ultrasonographic images of the tendon, echopatterns were quantified and categorised into four echo-types. Tendon abnormality was quantified as sum of echo-types III+IV. Furthermore, skin autofluorescence (AF) of the forearm (AF-value) was gathered. Results Twenty four type 2 diabetes patients, 24 controls, 24 type 1 diabetes patients and 20 controls were included. AF-value was higher in type 1 diabetes (1.55±0.17) than in their controls (1.39±0.18, p<0.001) and in type 2 diabetes (2.28±0.38) compared to their controls (1.84±0.32, p<0.001) Achilles tendons of type 2 diabetes patients contained more echo-types III+IV (14.1 ±7.9%) than matched controls (8.0±5.4%, p<0.001). There was a trend towards a difference in echo-types III+IV between type 1 diabetes patients (9.5 ±5.3%) and their controls (6.5±3.7%, p=0.055). In a stepwise linear regression analysis, body mass index (BMI) was moderately associated with tendon abnormality in patients with diabetes and controls (β=0.393, p<0.001). Conclusions Type 2, and possibly type 1, diabetes patients showed poorer ultrasonographic Achilles tendon structure that may be a risk factor for tendinopathy. Although markers for accumulation of advanced glycation end products were elevated in both diabetes populations, only BMI was associated with these abnormalities. [ABSTRACT FROM AUTHOR]

Background: Strict glycemic control during adolescence decreases the risk of developing complications later in life, even if this level of control is not maintained afterwards. However, the majority of adolescents with type 1 diabetes (T1D) are in poor control and so far medical or psychological interventions have shown limited success. Adolescence is characterized by major biological, psychosocial, cognitive and parent-child relationship changes and the complex interaction between these developmental trajectories, and its impact on health outcomes is still poorly understood. A specific topic of interest in this context is the timing of diagnosis. The longitudinal study DINO (Diabetes IN develOpment) aims to examine: 1) If and how the onset of T1D before vs. during puberty results in different outcomes of glycemic control, self-management, psychological functioning and diabetes-related quality of life. 2) The timing of onset of disturbed eating behavior, its risk factors and its prospective course in relation to glycemic and psychological consequences. 3) If and how the onset of T1D before vs. during puberty results in different family functioning and parental well-being. 4) If and how the cognitive development of youth with T1D relates to glycemic control and diabetes self-management. Methods/design: DINO, a longitudinal multi-center cohort study is conducted in youth with T1D in the age range 8-15 years at baseline. Participants will be divided into two subgroups: pre-pubertal and pubertal. Both groups will be followed for 3 years with assessments based on a bio-psychosocial model of diabetes, scheduled at baseline, 12 months, 24 months and 36 months examining the biological, psychosocial -including disturbed eating behaviors- and cognitive development, family functioning and parental well-being. Discussion: A better understanding of how the different trajectories affect one another will help to gain insight in the protective and risk factors for glycemic outcomes and in who needs which support at what moment in time. First results are expected in 2016. [ABSTRACT FROM AUTHOR]

Highlights: Skin autofluorescence is increased in diabetes, rises with age, and predicts diabetes‐related complications.Exposure to secondhand smoke, because one or more family members are smokers, further increases skin autofluorescence in children and young adults with type 1 diabetes.Elimination of passive smoking should be a goal in diabetes education. Association between age and skin autofluorescence (SAF), in arbitrary units (AU), in young people with type 1 diabetes exposed (black dots) and not exposed (open dots) to secondhand smoke. Regression lines show correlations between these parameters in exposed (solid line) and not exposed (dashed line) patients. [ABSTRACT FROM AUTHOR]

The article presents a part of the guidelines on pediatric diabetes in the International Society for Pediatric and Adolescent Diabetes (ISPAD) Clinical Practice Consensus Guidelines 2014 Compedium. It explores the recommendations for screening and monitoring of other complications and diabetes-related conditions in children and adolescents. It compares the grading system used in the ISPAD guidelines with that of the American Diabetes Association.

Background In young children with type 1 diabetes mellitus (T1DM), parents have complete responsibility for the diabetes-management. In toddlers and (pre)schoolers, the tasks needed to achieve optimal blood glucose control may interfere with normal developmental processes and could negatively affect the quality of parent-child interaction. Several observational instruments are available to measure the quality of the parent-child interaction. However, no observational instrument for diabetes-specific situations is available. Therefore, the aim of the present study was to develop a qualitative observation instrument, to be able to assess parent-child interaction during diabetes-specific situations. Methods First, in a pilot study (n = 15), the observation instrument was developed in four steps: (a) defining relevant diabetes-specific situations; (b) videotaping these situations; (c) describing all behaviors in a qualitative observation instrument; (d) evaluating usability and reliability. Next, we examined preliminary validity (total n = 77) by testing hypotheses about correlations between the observation instrument for diabetes-specific situations, a generic observation instrument and a behavioral questionnaire. Results The observation instrument to assess parent-child interaction during diabetes-specific situations, which consists of ten domains: "emotional involvement", "limit setting", "respect for autonomy", "quality of instruction", "negative behavior", "avoidance", "cooperative behavior", "child's response to injection", "emphasis on diabetes", and "mealtime structure", was developed for use during a mealtime situation (including glucose monitoring and insulin administration). Conclusions The present study showed encouraging indications for the usability and inter-rater reliability (weighted kappa was 0.73) of the qualitative observation instrument. Furthermore, promising indications for the preliminary validity of the observation instrument for diabetes-specific situations were found (r ranged between ∣.24∣ and ∣.45∣ for significant correlations and between ∣.10∣ and ∣.23∣ for non-significant trends). This observation instrument could be used in future research to (a) test whether parent-child interactions are associated with outcomes (like HbA1c levels and psychosocial functioning), and (b) evaluate interventions, aimed at optimizing the quality of parent-child interactions in families with a young child with T1DM. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim It is recommended to assess health-related quality of life ( HRQoL) in teenagers with diabetes as part of their ongoing medical care. Here, we describe the development and psychometric evaluation of the Monitoring Individual Needs in Diabetes Youth Questionnaire ( MY-Q), a multi-dimensional self-report HRQoL questionnaire designed for use in pediatric diabetes care. Design and methods In expert meetings, characteristics and domains of interest were defined. Existing questionnaires were reviewed, topics selected, and new items added, resulting in the 36-item MY-Q. To test face validity, we interviewed 22 teenagers. In addition, 84 teenagers with type 1 diabetes (age 10-18 yr) completed the MY-Q and Pediatric Quality of Life Inventory ( PedsQL) generic and diabetes-modules to examine psychometric properties. Hemoglobin A1c ( HbA1c) values were obtained by chart audit. Results The MY-Q consists of seven subscales (social impact, parents, diabetes control perceptions, responsibility, worries, treatment satisfaction, and body image and eating behavior) as well as general HRQoL and emotional well-being. Cronbach's alpha for the total scale was 0.80. Strong correlations between MY-Q total and PedsQL generic and diabetes-module scores (r = 0.58 and r = 0.71, p < 0.001) confirmed concurrent validity. Higher HbA1c was associated with lower diabetes control perceptions (r = −0.35, p = 0.001), worries (r = −0.24, p = 0.029), and body image and eating behavior (r = −0.26, p = 0.019) scores. Younger age was associated with higher diabetes control perceptions (r = −0.26, p = 0.020) and body image and eating behavior (r = −0.23, p = .038), and lower responsibility (r = 0.25, p = 0.027) scores. Conclusion The MY-Q is the first HRQoL questionnaire designed for use in clinical care. It has acceptable measurement properties and seems suitable for implementation in routine care of teenagers with diabetes. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim It is recommended to assess health-related quality of life ( HRQoL) in teenagers with diabetes as part of their ongoing medical care. Here, we describe the development and psychometric evaluation of the Monitoring Individual Needs in Diabetes Youth Questionnaire ( MY-Q), a multi-dimensional self-report HRQoL questionnaire designed for use in pediatric diabetes care. Design and methods In expert meetings, characteristics and domains of interest were defined. Existing questionnaires were reviewed, topics selected, and new items added, resulting in the 36-item MY-Q. To test face validity, we interviewed 22 teenagers. In addition, 84 teenagers with type 1 diabetes (age 10-18 yr) completed the MY-Q and Pediatric Quality of Life Inventory ( PedsQL) generic and diabetes-modules to examine psychometric properties. Hemoglobin A1c ( HbA1c) values were obtained by chart audit. Results The MY-Q consists of seven subscales (social impact, parents, diabetes control perceptions, responsibility, worries, treatment satisfaction, and body image and eating behavior) as well as general HRQoL and emotional well-being. Cronbach's alpha for the total scale was 0.80. Strong correlations between MY-Q total and PedsQL generic and diabetes-module scores (r = 0.58 and r = 0.71, p < 0.001) confirmed concurrent validity. Higher HbA1c was associated with lower diabetes control perceptions (r = −0.35, p = 0.001), worries (r = −0.24, p = 0.029), and body image and eating behavior (r = −0.26, p = 0.019) scores. Younger age was associated with higher diabetes control perceptions (r = −0.26, p = 0.020) and body image and eating behavior (r = −0.23, p = .038), and lower responsibility (r = 0.25, p = 0.027) scores. Conclusion The MY-Q is the first HRQoL questionnaire designed for use in clinical care. It has acceptable measurement properties and seems suitable for implementation in routine care of teenagers with diabetes. [ABSTRACT FROM AUTHOR]

Background: In young children with type 1 diabetes mellitus (T1DM) parents have full responsibility for the diabetes-management of their child (e.g. blood glucose monitoring, and administering insulin). Behavioral tasks in childhood, such as developing autonomy, and oppositional behavior (e.g. refusing food) may interfere with the diabetes-management to achieve an optimal blood glucose control. Furthermore, higher blood glucose levels are related to more behavioral problems. So parents might need to negotiate with their child on the diabetes-management to avoid this direct negative effect. This interference, the negotiations, and the parent's responsibility for diabetes may negatively affect the quality of parent-child interaction. Nevertheless, there is little knowledge about the quality of interaction between parents and young children with T1DM, and the possible impact this may have on glycemic control and psychosocial functioning of the child. While widely used global parent-child interaction observational methods are available, there is a need for an observational tool specifically tailored to the interaction patterns of parents and children with T1DM. The main aim of this study is to construct a disease-specific observational method to assess diabetes-specific parent-child interaction. Additional aim is to explore whether the quality of parent-child interactions is associated with the glycemic control, and psychosocial functioning (resilience, behavioral problems, and quality of life). Methods/Design: First, we will examine which situations are most suitable for observing diabetes-specific interactions. Then, these situations will be video-taped in a pilot study (N = 15). Observed behaviors are described into rating scales, with each scale describing characteristics of parent-child interactional behaviors. Next, we apply the observational tool on a larger scale for further evaluation of the instrument (N = 120). The parents are asked twice (with two years in between) to fill out questionnaires about psychosocial functioning of their child with T1DM. Furthermore, glycemic control (HbA1c) will be obtained from their medical records. Discussion: A disease-specific observational tool will enable the detailed assessment of the quality of diabetesspecific parent-child interactions. The availability of such a tool will facilitate future (intervention) studies that will yield more knowledge about impact of parent-child interactions on psychosocial functioning, and glycemic control of children with T1DM. [ABSTRACT FROM AUTHOR]

DAWN Youth Summit meetings in Berlin, in September 2007, and Budapest, in November 2008, brought together experts and ambassadors in childhood diabetes from many countries under the auspices of the International Diabetes Federation (IDF) and International Society for Pediatric and Adolescent Diabetes (ISPAD). The aims of these multidisciplinary international DAWN Youth meetings were to define joint goals and actions to improve psychosocial support for children and young people with diabetes and their families worldwide. The development of the IDF Youth Charter and the formation of the DAWN Youth initiative have enabled a much clearer understanding of the importance of psychosocial support for young people with diabetes and their families, and of the extent to which it is lacking throughout the world. Indeed, DAWN activities such as the Fact-Finding Survey (conducted to examine the legislative and administrative provisions relating to aspects of diabetes care in different countries) and the online WebTalk Study (examining the attitudes and views of youth with diabetes, parents of those with diabetes, and diabetes healthcare professionals) have been instrumental in this regard. The DAWN Youth Summits mobilized leaders in pediatric diabetes care to define the areas where specific improvements were realistically achievable. The DAWN Youth Summits were part of a series of international DAWN Youth dialog meetings and workshops held since late 2006, some coordinated with the Psychosocial Aspects of Diabetes (PSAD) Study Group under European Association for the Study of Diabetes (EASD) and some coordinated with the IDF Diabetes Youth Charter Working Group. The Summits brought together diabetes Youth Ambassadors (young people with diabetes who were able to contribute their own experiences and views), pediatric diabetologists, pediatric diabetes psychologists, diabetes anthropologists and sociologists, healthcare policymakers, parents of children with diabetes, and representatives of national patient associations, plus communication and media experts, and advisers to the World Health Organization. Discussion at the Summits centered on the five action areas for DAWN Youth: • Improve support for children with diabetes in schools. • Provide age-appropriate education and psychosocial diabetes care. • Provide support for parents and families. • Provide peer support and networking for young people with diabetes. • Address childhood obesity and type 2 diabetes in youth. Whereas the increasing prevalence of childhood obesity is considered an important future area of action for DAWN Youth, the focus of the current article is on the first four areas. [ABSTRACT FROM PUBLISHER]

The article reports on the DAWN Youth program, which focuses on improving the level of psychosocial support for children, adolescents, and young adults with diabetes, and their families. The objective of the program is to improve the health and the quality of the life of young people who are suffering from diabetes throughout the world. DAWN Youth has an International Advisory Board along with national DAWN Youth Boards present in various countries.

OBJECTIVE--There is evidence that monocytes of patients with type 1 diabetes show proinflammatory activation and disturbed migration/adhesion, but the evidence is inconsistent. Our hypothesis is that monocytes are distinctly activated/disturbed in different subforms of autoimmune diabetes. RESEARCH DESIGN AND METHODS--We studied patterns of inflammatory gene expression in monocytes of patients with type 1 diabetes (juvenile onset, n = 30; adult onset, n = 30) and latent autoimmune diabetes of the adult (LADA) (n = 30) (controls subjects, n = 49; type 2 diabetic patients, n = 30) using quantitative PCR. We tested 25 selected genes: 12 genes detected in a prestudy via whole-genome analyses plus an additional 13 genes identified as part of a monocyte inflammatory signature previously reported. RESULTS--We identified two distinct monocyte gene expression clusters in autoimmune diabetes. One cluster (comprising 12 proinflammatory cytokine/compound genes with a putative key gene PDE4B) was detected in 60% of LADA and 28% of adult-onset type 1 diabetic patients but in only 10% of juvenile-onset type 1 diabetic patients. A second cluster (comprising 10 chemotaxis, adhesion, motility, and metabolism genes) was detected in 43% of juvenile-onset type 1 diabetic and 33% of LADA patients but in only 9% of adult-onset type 1 diabetic patients. CONCLUSIONS--Subgroups of type 1 diabetic patients show an abnormal monocyte gene expression with two profiles, supporting a concept of heterogeneity in the pathogenesis of autoimmune diabetes only partly overlapping with the presently known diagnostic categories. Diabetes 57:2768-2773, 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE--We investigated the association of anti-inflammatory cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), adiponectin, proinflammatory cytokines IL-1β, IL-6, and CCL2, and tumor necrosis factor-α with β-cell function, metabolic status, and clinical remission in patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS--Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide, blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months after diagnosis. Analyses were adjusted for sex, age, and BMI percentile. RESULTS--Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 (P = 0.0009) and 12 (P = 0.009) months. The beneficial association of IL-1ra on β-cell function was complemented by the negative association of IL-1β with C-peptide after 1 month (P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12 months (P < 0.05) and positively correlated with A1C after 1 month (P = 0.0004). Proinflammatory IL-6 was elevated in patients with good metabolic control after 1 month (P = 0.009) and showed a positive association with blood glucose disposal after 12 months (P = 0.047). CONCLUSIONS--IL-1ra is associated with preserved β-cell capacity in type 1 diabetes. This novel finding indicates that administration of IL-1ra, successfully improving β-cell function in type 2 diabetes, may also be a new therapeutic approach in type 1 diabetes. The relation of adiponectin and IL-6 with remission and metabolic status transfers observations from in vitro and animal models into the human situation in vivo. [ABSTRACT FROM AUTHOR]

Objective: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required.Research Design and Methods: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998.Results: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations.Conclusions: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes. [ABSTRACT FROM AUTHOR]

The optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial. Therefore this multicentre study was performed in adolescents over a 3-year period to assess metabolic control, severe hypoglycaemia, and weight gain in relation to insulin injection regimens. Out of 2873 children and adolescents in an international survey in 1995, 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3 ± 2.2 years) were restudied in 1998, relating insulin regimens to HbA[sub 1c] measured in a central laboratory. In addition, the daily dose of insulin, changes in body mass index (BMI), and events of severe hypoglycaemia were evaluated. Over 3 years, the use of multiple injection regimens increased from 42% to 71%: 251 patients remained on twice daily insulin, 365 remained on multiple injections and 256 shifted from twice daily insulin to multiple injections. In all three subgroups an increase in insulin dose, a deterioration of metabolic control, and an increase in BMI were observed. Metabolic control deteriorated less than expected over 3 years during adolescence (HbA[sub 1c] 1995: 8.7 ± 1.6%; 1998 observed: 8.9 ± 1.6%, HbA[sub 1c] expected for 1998: 9.0%). BMI increased more than expected, the increase was greatest in patients switching from twice daily to multiple injections, and higher in females compared to males. Conclusion: in this international study, metabolic control was unsatisfactory in many adolescents with type 1 diabetes irrespective of the insulin regimen. No improvement in metabolic control was observed in this cross-sectional survey, over 3 years in any of the subgroups. Even the group switching from twice to multiple injections did not improve blood glucose control and the increase in body mass index was most pronounced in this group. Conclusive evidence, however, should be based on prospectively planned, randomised therapeutic trials in paediatric patients. [ABSTRACT FROM AUTHOR]

Deals with a study which assessed the relations between metabolic control and the quality of life of adolescents with diabetes and their families. Research design and methods; Results; Conclusions.

Objective: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period.Research Design and Methods: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years).Results: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia.Conclusions: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few. [ABSTRACT FROM AUTHOR]

Objective: To study the association of autoantibodies against a 38-kDa glycated islet cell membrane-associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification.Research Design and Methods: Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays.Results: GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for > or = 1 other autoantibody.Conclusions: GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs. [ABSTRACT FROM AUTHOR]

OBJECTIVETo assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGNIn a prospective, randomised double-blind, dose–response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m2 body surface·day)]. PATIENTSSeventy-eight children with short stature (height SD-score < - 1·88) born small for gestational age (birth length SD-score < - 1·88) being all prepubertal with a mean (SD) chronological age of 7·3 (2·2) years before start of treatment. MEASUREMENTSGlucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA1c) were measured before and during 6 years of GH treatment. RESULTSBefore treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7·8 mmol/l but below 11·1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0·5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA1c levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA1c levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to... [ABSTRACT FROM AUTHOR]

Pancreatic agenesis is a rare condition, of which only a limited number of cases have been described. One recent paper reported a homozygous mutation in the pancreatic duodenal homeobox gene 1 (PDX-1) in a child with pancreatic agenesis. We report a 6-year-old boy with pancreatic agenesis, treated medically, without abnormalities in the PDX-1 gene coding sequence and with normal gastroduodenal endocrine cell distribution. Genes other than PDX-1 also appear to be involved in human pancreatic agenesis. [ABSTRACT FROM AUTHOR]

Investigates the effect of supraphysiological dosage growth hormone dosages on carbohydrate metabolism in girls with Turner syndrome. Importance of glucose and insulin concentration during oral glucose tolerance test; Observation of growth hormone injections; Performance of cyclical progestagen therapy.

The article focuses on the influence of the efforts made by the DAWN Youth International Advisory Group on the objectives of healthcare policymakers at the government levels in Italy regarding diabetes in young people. The overall goal of the Italian government's policy for diabetes is to set in motion a general cultural change from curing the disease to taking care.