Motivational interviewing from the paediatricians' perspective: assessments after a 2-day training for physicians caring for adolescents with chronic medical conditions (CMCs).

BACKGROUND: Counselling adolescents with chronic medical conditions (CMCs) can be challenging regarding suitable interviewing skills and clinicians' attitudes toward the patient. Successful communication can be a key element of treatment. Motivational Interviewing (MI) is broadly applicable in managing behavioural problems and diseases by increasing patient motivation for lifestyle changes. However, data concerning the applicability, feasibility and implementation of MI sessions in everyday practice are missing from the physicians' point of view. METHOD: The present study was conducted as a mixed methods design. Twenty paediatricians were randomized to a 2-day MI course followed by MI consultations. Data were collected through a questionnaire one year after MI training. Factors for effective training and possible barriers to successful use of MI were examined. RESULTS: Completed questionnaires were returned by 19 of 20 paediatricians. The paediatricians' experiences with MI demonstrate that MI is regarded as a valuable tool when working with adolescents with CMCs. 95% of all respondents reported that they found MI education necessary for their clinical work and were using it also outside the COACH-MI study context. 73.7% percent saw potential to strengthen the connection to their patients by using MI. The doctors were already using more MI conversation techniques after a 2-day MI course. Obstacles were seen in the short training, the lack of time and missing undisturbed environment (interruptions by telephone, staff, etc.) during clinical flow. CONCLUSIONS: MI techniques are not yet a regular part of medical training. However, a 2-day MI course was rated effective and provided a lasting impact by physicians caring for children and adolescents with chronic medical conditions (CMCs), although booster sessions should be offered regularly. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (DRKS00014043) on 26/04/2018.

Neutropenia Occurs More Often Under Carbimazole than Under Methimazole Treatment in Pediatric Graves' Disease Patients.

Background: Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. Methods: We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Results: Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; p = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; p = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10-1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger (p = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; n = 20/40) than in those receiving MMI (16.5%; n = 18/110; p = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); p = 0.004. Conclusions: Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD.

The Impact of COVID-19 Pandemic on Mental Health of Adolescents With Chronic Medical Conditions: Findings From a German Pediatric Outpatient Clinic.

PURPOSE: The impact of the COVID-19 pandemic on the mental health of adolescents is of great concern, especially in the vulnerable group of adolescents with chronic medical conditions. The aim of this study was to examine this impact on the mental health of adolescents with chronic medical conditions treated in a German pediatric outpatient clinic. METHODS: Changes in the mental health status of adolescents with chronic medical conditions treated in a German pediatric outpatient clinic during the COVID-19 pandemic were explored via validated screening tools for anxiety and depression. RESULTS: The relative risk for adolescents with chronic medical conditions to develop clinically relevant symptoms of anxiety or depression was significantly higher (odds ratio 1,78 [confidence interval 1.06-3.04]) during the pandemic. DISCUSSION: This study identifies the COVID-19 pandemic as a potential additional risk for adolescents with chronic medical conditions to develop clinically relevant signs of anxiety or depression.

Testing a model of benefit-finding and growth in youths with chronic health conditions.

BACKGROUND: The experience of benefit-finding and growth (BFG), defined as perceiving positive life changes resulting from adversity, is increasingly studied among youths with chronic health conditions (CCs). However, empirical evidence is scarce for explaining individual differences in BFG. The study aimed to test a model of BFG, including an interplay of personal and environmental factors and coping processes. METHODS: A sample of N = 498 youths (12-21 years) recruited from three German patient registries for CCs (type 1 diabetes: n = 388, juvenile idiopathic arthritis: n = 82, cystic fibrosis: n = 28) completed a questionnaire including self-reported optimism, social support from parents and peers, coping strategies, and BFG. The model was created to reflect the theoretical assumptions of the Life Crisis and Personal Growth model and current empirical evidence. Structural equation modeling was conducted to evaluate the incremental explanatory power of optimism, peer group integration, parental support, acceptance, cognitive reappraisal, and seeking social support over and above sociodemographic and disease-related characteristics. RESULTS: The model (CFI = 0.93; RMSEA = 0.04; SRMR = 0.05) explained 32% of the variance in BFG. Controlling for sociodemographic and disease-related characteristics, acceptance, cognitive reappraisal, and seeking social support were directly and positively linked to BFG. All tested coping strategies significantly mediated the association between optimism and BFG, whereas seeking social support significantly mediated the relation between peer group integration and BFG. DISCUSSION: The study stresses the prominent role of emotion-focused coping strategies and peer group integration in enhancing BFG in youths with CCs. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021.

Outpatient screening for anxiety and depression symptoms in adolescents with type 1 diabetes - a cross-sectional survey.

BACKGROUND: The daily demands of type 1 diabetes management may jeopardize adolescents' mental health. We aimed to assess anxiety and depression symptoms by broad-scale, tablet-based outpatient screening in adolescents with type 1 diabetes in Germany. METHODS: Adolescent patients with type 1 diabetes mellitus (n = 2,394; mean age 15.4 y [SD 2.0]; 50.7% male) were screened for anxiety (GAD-7) and depression symptoms (PHQ-9) by self-report questionnaires and linked to clinical data from the DPV patient registry. Logistic regression was used to estimate the contribution of clinical parameters to positive screening results. RESULTS: Altogether, 30.2% showed a positive screening (score ≥ 7 in either test), and 11.3% reported suicidal ideations or self-harm. Patients with anxiety and depression symptoms were older (15.7 y [CI 15.5-15.8] vs. 15.3 y [CI 15.2-15.4]; p < 0.0001), had higher HbA1c levels (7.9% [CI 7.8-8.0] (63 mmol/mol) vs. 7.5% [CI 7.4-7.5] (58 mmol/mol); p < 0.0001), and had higher hospitalization rates. Females (adjusted odds ratio (aOR) 2.66 [CI 2.21-3.19]; p < 0.0001), patients > 15 years (aOR 1.40 [1.16-1.68]; p < 0.001), who were overweight (aOR 1.40 [CI 1.14-1.71]; p = 0.001), with HbA1c > 9% (> 75 mmol/mol; aOR 2.58 [1.83-3.64]; each p < 0.0001), with a migration background (aOR 1.46 [CI 1.17-1.81]; p < 0.001), or smoking (aOR 2.72 [CI 1.41-5.23]; p = 0.003) had a higher risk. Regular exercise was a significant protective factor (aOR 0.65 [CI 0.51-0.82]; p < 0.001). Advanced diabetes technologies did not influence screening outcomes. CONCLUSIONS: Electronic mental health screening was implemented in 42 centers in parallel, and outcomes showed an association with clinical parameters from sociodemographic, lifestyle, and diabetes-related data. It should be integrated into holistic patient counseling, enabling early recognition of mild mental health symptoms for preventive measures. Females were disproportionally adversely affected. The use of advanced diabetes technologies did not yet reduce the odds of anxiety and depression symptoms in this cross-sectional assessment.

Strengthening the Resilience of Children and Adolescents during a Pandemic: A Scoping Review on Eligible Interventions.

BACKGROUND: The COVID-19 pandemic dramatically affects children's and adolescents' mental health. The accumulation of stress factors and a lack of social support complicate a healthy development. Since the beginning of the pandemic, there has been almost a doubling of mental health problems in children and adolescents. Promoting resilience is a possible approach to reduce the incidence of mental health problems despite these adverse circumstances. OBJECTIVES: This literature search aims at identifying and evaluating interventions to promote resilience mechanisms, with a special focus on feasibility in a crisis situation. MATERIALS AND METHODS: This scoping review is based on a systematic literature search including the databases Cochrane Library, PubMed, Psyc-Info, Psyndex and Google Scholar (2006-2020). Of 1733 identified articles 75 were included. RESULTS: Out of 72 identified intervention studies 28% were feasible under pandemic conditions. The most effective resilience trainings seem to be individualized interventions using cognitive behavioral therapy elements. However, many approaches primarily show short-term success. DISCUSSION: Few evidence-based programs are feasible online or under pandemic restrictions. Most of them show short-term effects and focus on parents and individuals. Multiple programs are ready for use, but still lack proof of efficacy. The development and improvement of (digital) resilience interventions should be an essential part of preventive health care, especially for risk groups. HINTERGRUND: Die COVID-19-Pandemie beeinflusst die mentale Gesundheit von Kindern und Jugendlichen auf dramatische Weise. Durch eine Akkumulation von Belastungsfaktoren und das Wegfallen sozialer Unterstützung ist eine regelrechte Entwicklung erschwert. Seit Beginn der Pandemie kam es nahezu zu einer Verdopplung der psychischen Auffälligkeiten. Die Förderung der Resilienz kann ein Ansatz sein, das Auftreten von psychischen Auffälligkeiten trotz dieser widrigen Umstände zu vermindern. ZIEL DER ARBEIT: Ziel dieser Literaturrecherche ist die Identifikation und Bewertung von Interventionen zur Förderung von Resilienzmechanismen, mit Fokus auf die Durchführbarkeit unter Krisenbedingungen. MATERIAL UND METHODEN: Dieses Scoping Review basiert auf einer systematischen Literaturrecherche der Datenbanken Cochrane Library, PubMed, Psyc-Info, Psyndex sowie Google Scholar (2006-2021). Von der insgesamt 1733 Artikel umfassenden Suche wurden 75 Artikel eingeschlossen. ERGEBNISSE: Von 72 identifizierten Interventionsstudien sind 28% unter Pandemiebedingungen durchführbar. Die wirksamsten Resilienztrainings scheinen individualisierte Interventionen mit Elementen der kognitiven Verhaltenstherapie zu sein. Viele Ansätze zeigen jedoch in erster Linie kurzfristige Erfolge. DISKUSSION: Nur wenige evidenzbasierte Programme sind online oder unter Pandemiebedingungen verfügbar. Die meisten von ihnen zeigen kurzfristige Effekte und konzentrieren sich auf Eltern und Einzelpersonen. Zahlreiche Programme sind nutzbar, allerdings fehlt häufig ein Evidenznachweis. Die Entwicklung und Verbesserung von (digitalen) Resilienzmaßnahmen sollte ein wesentlicher Bestandteil der präventiven Gesundheitsversorgung sein, insbesondere für Risikogruppen.

Anxiety, depression, and quality of life in parents of children with congenital hyperinsulinism.

This study aimed to assess mental health, family burden, and quality of life (PQoL) in parents of children with persistent congenital hyperinsulinism (CHI). Forty-eight individual CHI parents (75% female) completed self-reported questionnaires and screening tools for anxiety (GAD-7), depression (PHQ-8), PQoL (ULQIE), and family burden (FaBeL). Additional data on sociodemographics, social support, and child- and disease-related data were recorded. 29.8% of parents showed major depressive symptoms and 38.3% had a probable general anxiety disorder, including 20.8% who had both. The family burden was moderate and assessment of PQoL yielded average scores. Neurological impairment in an affected child (p = .002 and p < .001, respectively) and lower working hours (p = .001 and p = .012, respectively) were the strongest predictors of worse GAD-7 and PHQ-8 scores. Furthermore, lower working hours (p = .012) and comorbidities in the affected child (p = .007) were significantly associated with lower PQoL. Mothers had worse GAD-7 scores (p = .006) and lower PQoL (p = .035) than fathers. Indication of sleep disturbance was associated with worse PHQ-8 scores (p = .003), higher family burden (p = .039), and reduced PQoL (p = .003). A higher number of caretakers besides parents was associated with decreased family burden (p = .019), improved PQoL (p < .001), and lower scores for anxiety (p = .016) and depressive (p = .021) symptoms.    Conclusion: Symptoms of depression and anxiety are alarmingly prevalent in parents of children with CHI. Psychological screening of parents should be initiated to ensure early identification of psychological strains and psychosocial support should be offered as needed. A good support network and regular work activities can improve parental mental health and well-being. What is Known: • Psychosocial strains and reduced quality of life are common in parents of chronically ill children. What is New: • In this first study evaluating mental health, family burden, and quality of life in parents of children with congenital hyperinsulinism (CHI), symptoms of depression and anxiety were alarmingly prevalent. • Parents of children with CHI should receive regular psychological screening and psychosocial support should be offered as needed. A good support network and regular work activities can improve parental mental health and well-being.

Interleukin-7 and soluble Interleukin-7 receptor levels in type 1 diabetes - Impact of IL7RA polymorphisms, HLA risk genotypes and clinical features.

High soluble IL-7 receptor (sIL-7R) serum levels and associated single nucleotide polymorphisms in the IL7RA gene were found in autoimmune diseases including type 1 diabetes. Further determinants on sIL-7R and IL-7 availability as well as changes during type 1 diabetes disease course remain elusive. Here we performed multiparameter analysis to identify influential genetic and disease-associated factors on sIL-7R and IL-7 serum levels during type 1 diabetes disease course (239 children) and in healthy controls (101 children). We found higher sIL-7R serum concentrations at type 1 diabetes onset and decreasing levels during therapy whereas IL-7 was only higher in long term patients as compared to controls. Multiple linear regression analyses revealed several factors, including IL7RA SNP rs6897932 and HLA risk haplotypes, influencing sIL-7R levels but not IL-7, which was solely associated with the sIL-7R. This study revealed unexpected complexity in the regulation of the sIL-7R but not for IL-7.

Long-Term Efficacy of T3 Analogue Triac in Children and Adults With MCT8 Deficiency: A Real-Life Retrospective Cohort Study.

CONTEXT: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. OBJECTIVE: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. METHODS: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. RESULTS: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. CONCLUSIONS: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.

Next Generation Sequencing Identifies the HLA-DQA1*03:03 Allele in the Type 1 Diabetes Risk-Associated HLA-DQ8 Serotype.

The highest genetic type 1 diabetes risk is conferred by HLA class II haplotypes defined by alleles at the HLA-DR and -DQ loci. The combination of HLA-DQA1*03:01 and DQB1*03:02 alleles (summarized as 'HLA-DQ8') is reported to be among the two most prevalent HLA class II haplotypes in Caucasian type 1 diabetes patients. This classification is based on conventional genotyping of exon 2 of the DQ gene locus and excludes exon 3. In this study, HLA genotyping on the type 1 diabetes susceptibility loci HLA-DRB1, DQA1 and DQB1 was performed using a high-resolution next generation sequencing method. In addition to the routinely examined exon 2, exon 3 was also sequenced. Samples from 229 children with type 1 diabetes were included and compared to a cohort of 9,786 controls. In addition to previously described HLA-DQ haplotypes in type 1 diabetes patients, we found that as well as HLA-DQA1*03:01,HLA-DQA1*03:03 also contributed to HLA-DQ8. HLA-DQA1*03:03 differs from HLA-DQA1*03:01 by one nucleotide substitution in exon 3 at position 160, leading to a single amino acid replacement. DRB1*04:05 was exclusively associated with DQA1*03:03 whereas the DRB1*04:01 haplotype comprised either DQA1*03:01 or DQA1*03:03. Significantly increased type 1 diabetes risk was confirmed for all these haplotypes with only minor differences between DQA1*03:01 and DQA1*03:03 alleles. This study identified the HLA-DQA1*03:03 allele as an addition to the already known type 1 diabetes risk haplotypes, and can contribute to more precise HLA genotyping approaches.

Efficacy of Motivational Interviewing to Improve Utilization of Mental Health Services Among Youths With Chronic Medical Conditions: A Cluster Randomized Clinical Trial.

Importance: Despite the high prevalence of anxiety and depression in youths with chronic medical conditions (CMCs), physicians encounter substantial barriers in motivating these patients to access mental health care services. Objective: To determine the efficacy of motivational interviewing (MI) training for pediatricians in increasing youths' use of mental health care. Design, Setting, and Participants: The COACH-MI (Chronic Conditions in Adolescents: Implementation and Evaluation of Patient-Centered Collaborative Healthcare-Motivational Interviewing) study was a single-center cluster randomized clinical trial at the University Children's Hospital specialized outpatient clinics in Düsseldorf, Germany. Treating pediatricians were cluster randomized to a 2-day MI workshop or treatment as usual (TAU). Patient recruitment and MI conversations occurred between April 2018 and May 2020 with 6-month follow-up and 1-year rescreening. Participants were youths aged 12 to 20 years with CMCs and comorbid symptoms of anxiety and depression; they were advised by their MI-trained or untrained physicians to access psychological counseling services. Statistical analysis was performed from October 2020 to April 2021. Interventions: MI physicians were trained through a 2-day, certified MI training course; they recommended use of mental health care services during routine clinical appointments. Main Outcomes and Measures: The primary outcome of uptake of mental health care services within the 6-month follow-up was analyzed using a logistic mixed model, adjusted for the data's cluster structure. Uptake of mental health services was defined as making at least 1 appointment by the 6-month follow-up. Results: Among 164 youths with CMCs and conspicuous anxiety or depression screening, 97 (59%) were female, 94 (57%) had MI, and 70 (43%) had TAU; the mean (SD) age was 15.2 (1.9) years. Compared with patients receiving TAU, the difference in mental health care use at 6 months among patients whose physicians had undergone MI training was not statistically significant (odds ratio [OR], 1.96; 95% CI, 0.98-3.92; P = .06). The effect was moderated by the subjective burden of disease (F2,158 = 3.42; P = .04). Counseling with an MI-trained physician also led to lower anxiety symptom scores at 1-year rescreening (F1,130 = 4.11; P = .045). MI training was associated with longer conversations between patients and physicians (30.3 [16.7] minutes vs 16.8 [12.5] minutes; P < .001), and conversation length significantly influenced uptake rates across conditions (OR, 1.03; 95% CI, 1.01-1.06; P = .005). Conclusions and Relevance: In this study, use of MI in specialized pediatric consultations did not increase the use of mental health care services among youths with CMCs but did lead to longer patient-physician conversations and lower anxiety scores at 1 year. Additional research is required to determine whether varying scope and duration of MI training for physicians could encourage youths with CMCs to seek counseling and thus improve integrated care models. Trial Registration: German Trials Registry: DRKS00014043.

Interleukin-7-dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes.

The important role of IL-7 in the generation of self-reactive T-cells in autoimmune diseases is well established. Recent studies on autoimmunity-associated genetic polymorphisms indicated that differential IL-7 receptor (IL-7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL-7-mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL-7-mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t-distributed Stochastic Neighbor-Embedded (t-SNE)-analyses. IL-7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL-7, we detected lower monocyte IL-7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL-7 stimulation. t-SNE analyses revealed IL-7-dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA-DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL-7 and CD40/IL-7R co-expression differed between patients and controls. This study shows the unique effects of IL-7 on monocyte phenotype and functions. Lower IL-7R expression on IL-7-induced CD40high monocytes and impaired IL-7 response characterize monocytes from patients with type 1 diabetes.

A prospective investigation of developmental trajectories of psychosocial adjustment in adolescents facing a chronic condition - study protocol of an observational, multi-center study.

BACKGROUND: Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions. METHODS/DESIGN: We plan to consecutively recruit N = 450 adolescents (12-21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups - "inconspicuous" (PHQ-9 and GAD-7 < 7) vs. "conspicuous" (PHQ-9 or GAD-7 ≥ 7) - participating in a prospective online survey at baseline and 12-month follow-up. At two time points (T1, T2), we assess (1) intra- and interpersonal resiliency factors, (2) coping strategies, and (3) health-related quality of life, well-being, satisfaction with life, anxiety and depression. Using a cross-lagged panel design, we will examine the bidirectional longitudinal relations between resiliency factors and coping strategies, psychological adaptation, and psychosocial adjustment. To monitor Covid-19 pandemic effects, participants are also invited to take part in an intermediate online survey. DISCUSSION: The study will provide a deeper understanding of adaptive, potentially modifiable processes and will therefore help to develop novel, tailored interventions supporting a positive adaptation in youths with a chronic condition. These strategies should not only support those at risk but also promote the maintenance of a successful adaptation. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00025125 . Registered on May 17, 2021.

CD5-expressing CD8+ T-cell subsets differ between children with type 1 diabetes and controls.

Different lymphocyte subsets are involved in autoimmune pathogenesis of type 1 diabetes (T1D). Previous studies suggested a role of CD5-expressing T and B cells including rare unconventional lymphocytes with combined T- and B-cell features [dual expressing (DE) cells]. We performed algorithm-supported multiparameter flow cytometry and quantitative PCR to investigate immune cell subsets and DE cells in children with T1D (n = 20) and matched controls (n = 20). Comparisons of conventional immune cells detected increased proportions of CD3+ T cells in T1D patients, whereas CD19+ B-cell proportions were comparable to controls. Self-organizing maps for flow cytometry analyses (FlowSOM) showed highly similar CD5-expressing B-cell subsets and no differences for DE cells were detected between the study groups by flow cytometry or specific quantitative PCR. Notably, differences in CD8+ T cells were indicated by FlowSOM and similarity-based t-distributed stochastic neighbor embedding (tSNE) analyses. Study group comparisons confirmed significantly reduced CD8+ T-cell proportions with moderate or low CD5 expression in T1D patients. Finally, in vitro experiments showed stable CD5 expression differences of CD8+ T cells after T-cell activation, cytokine stimulation and culture. We observed differences of T-cell coreceptor CD5 expression in T1D patients with potential relevance for immune regulation of CD8+ T-cell activation.

Challenges in management of transient hyperinsulinism - a retrospective analysis of 36 severely affected children.

OBJECTIVES: Transient hyperinsulinism (THI) is a hypoglycemia disorder which resolves spontaneously within the first weeks or months of life. The pathomechanism of THI is not elucidated yet; however, it is known that perinatal stress predisposes for THI. We aimed to characterize the clinical phenotype and treatment of children with THI, and to identify options for improved management. METHODS: A retrospective analysis of 36 children with THI treated at the University Children's Hospital Düsseldorf between 2007 and 2019 was performed. RESULTS: All children had risk factors for neonatal hypoglycemia or indicators of perinatal stress. Eighty three percent were diagnosed with hypoglycemia on day of life (DOL)1. None of the six diagnosed later had routine blood glucose screening and showed significantly lower blood glucose levels at the time of first blood glucose measurement compared to the children diagnosed on DOL1. Ninety seven percent of all children received intravenous glucose, 42% received continuous glucagon and 81% were started on diazoxide. Diazoxide withdrawal and subsequent fasting tests lacked standardization and were based on clinical experience. Three patients had a subsequent episode of hypoglycemia, after fasting studies only demonstrated "clinical" remission without proving the ability to ketogenesis. CONCLUSIONS: Any kind of perinatal stress might pose a risk to develop THI, and postnatal monitoring for hypoglycemia still needs to be improved. Diazoxide is effective in children with THI; however, further studies are needed to guide the development of criteria and procedures for the initiation and discontinuation of treatment. Furthermore, establishing consensus diagnostic criteria/definitions for THI would improve comparability between studies.

Worse glycemic control, higher rates of diabetic ketoacidosis, and more hospitalizations in children, adolescents, and young adults with type 1 diabetes and anxiety disorders.

The aim of the study was to explore the metabolic characteristics and outcome parameters in youth with type 1 diabetes and anxiety disorders. HbA1c levels, rates of severe hypoglycemia, diabetic ketoacidosis (DKA), and hospital admission in children, adolescents, and young adults with type 1 diabetes and an anxiety disorder from 431 diabetes-care-centers participating in the nationwide German/Austrian/Swiss/Luxembourgian diabetes survey DPV were analyzed and compared with youth without anxiety disorders. Children, adolescents, and young adults with type 1 diabetes and anxiety disorders (n = 1325) had significantly higher HbA1c (8.5% vs. 8.2%), higher rates of DKA (4.2 vs. 2.5 per 100 patient-years), and higher hospital admission rates (63.6 vs. 40.0 per 100 patient-years) than youth without anxiety disorders (all p < 0.001). Rates of severe hypoglycemia did not differ. Individuals with anxiety disorders other than needle phobia (n = 771) had higher rates of DKA compared to those without anxiety disorders (4.2 vs. 2.5 per 100 patient-years, p = 0.003) whereas the rate of DKA in individuals with needle phobia (n = 555) was not significantly different compared to those without anxiety disorders. Children, adolescents, and young adults with anxiety disorders other than needle phobia had higher hospitalization rates (73.7 vs. 51.4 per 100 patient-years) and more inpatient days (13.2 vs. 10.1 days) compared to those with needle phobia (all p < 0.001). Children, adolescents, and young adults with type 1 diabetes and anxiety disorders had worse glycemic control, higher rates of DKA, and more hospitalizations compared to those without anxiety disorders. Because of the considerable consequences, clinicians should screen for comorbid anxiety disorders in youth with type 1 diabetes.

Non-suicidal self-injury in adolescents and young adults with type 1 diabetes: clinical characteristics from a German diabetes-patient registry (DPV).

The aim was to examine the relations between non-suicidal self-injury (NSSI) and clinical parameters as well as other psychiatric comorbidities in adolescents and young adults with type 1 diabetes mellitus (T1D). Patients aged 8-<=25 years with T1D and documented NSSI from the DPV database (n=167) were compared to a control group with T1D without NSSI or other psychiatric comorbidities (n=76,050) using multivariable regression models, adjusted for demographics. Clinical diabetes-related outcomes (haemoglobin A1c (HbA1c), daily insulin dose, diabetic ketoacidosis (DKA), hypoglycaemia, number of hospital days, number of hospital admissions) were analysed. NSSI patients had significantly higher HbA1c (%): (+1.1 [0.8; 1.4]), higher daily insulin doses: (+0.08 (U/kg), [0.02; 0.13]), more DKA events per patient year: (+1.79 [1.22; 2.37]), more hospital days per patient year: (+0.25 [0.20; 0.29]) and more frequent hospital admissions per patient year: (+0.93 [0.79; 1.06]) compared to T1D patients without NSSI or other psychiatric comorbidities (differences of adjusted estimates [confidence interval]). This is the first study to investigate the association between NSSI and T1D. We revealed that NSSI is significantly related to diabetes outcomes in adolescent T1D patients. There should be an increased awareness for NSSI in the care for adolescents and young adults with T1D.

Continuous Glucose Monitoring in Adults with Type 1 Diabetes: Real-World Data from the German/Austrian Prospective Diabetes Follow-Up Registry.

Background: To analyze key indicators of metabolic control in adults with type 1 diabetes (T1D) using real-time or intermittent scanning continuous glucose monitoring (rtCGM/iscCGM) during real-life care, based on the German/Austrian/Swiss Prospective Diabetes Follow-up (DPV) registry. Methods: Cross-sectional analysis including 233 adults with T1D using CGM. We assessed CGM metrics by gender, age group (18 to <30 years vs. ≥30 years), insulin delivery method (multiple daily injections vs. continuous subcutaneous insulin infusion [CSII]) and sensor type (iscCGM vs. rtCGM), working days versus weekends, and daytime versus night-time using multivariable linear regression models (adjusted for demographic variables) or Wilcoxon signed-rank test. Results: Overall, 79/21% of T1D patients used iscCGM/rtCGM. Those aged ≥30 years spent more time in range (TIR [70-180 mg/dL] 54% vs. 49%) and hypoglycemic range <70 mg/dL (7% vs. 5%), less time in hyperglycemic range >180 mg/dL (38% vs. 46%) and had a lower glucose variability (coefficient of variation [CV] 36% vs. 37%) compared with adults aged <30 years. We found no significant differences between genders. Multivariable regression models revealed the highest Time In Range (TIR) and lowest time with sensor glucose >250 mg/dL, CV and daytime-night-time differences in those treated with CSII and rtCGM. Glucose profiles were slightly more favorable on working days. Conclusions: In our real-world data, rtCGM versus iscCGM was associated with a higher percentage of TIR and improved metabolic stability. Differences in ambulatory glucose profiles on working and weekend days may indicate lifestyle habits affecting glycemic stability. Real-life CGM results should be included in benchmarking reports in addition to hemoglobin A1c (HbA1c) and history of hypoglycemia.

Course of Disordered Eating Behavior in Young People With Early-Onset Type I Diabetes: Prevalence, Symptoms, and Transition Probabilities.

PURPOSE: The aims of this study were to analyze the prevalence and course of disordered eating behavior (DEB) in adolescents with intensively treated type I diabetes, describe differences in age-specific DEB symptoms, and identify predictors of current DEB. METHODS: Data were taken from 332/218 11- to 27-year-old participants (55.7% girls/women, mean age [SD] 17.8 [3.4] years, mean diabetes duration 14.9 [3.0] years) of two/three surveys of a Germany-wide longitudinal study on early-onset and long duration diabetes, respectively. A diabetes-adapted version of the SCOFF questionnaire was used to assess DEB. Both screening-based overall and age- and sex-specific prevalence of DEB and its symptoms were determined. To estimate transition probabilities between DEB states, first-order Markov transition models were implemented adjusting for previous sociodemographic, socioeconomic, and diabetes-specific covariates. RESULTS: The overall screening-based DEB prevalence among all 1,318 observations was 10.8% (95% confidence interval [CI]: 9.2%, 12.6%) with age-specific differences in symptom prevalence. Transition probabilities for developing/persistent DEB were twofold higher among female than male participants (risk ratio [RR] 2.3 [1.4, 3.9]/2.1 [1.3, 3.4]). In multiple adjusted regression, previous DEB (odds ratio [OR] 2.8 [95% CI 1.4, 5.6]), follow-up time (ORper 1-year increase 3.4 [1.4, 8.0]), and sex (ORgirls/women 2.1 [1.1, 3.9]) were the most important predictors of current DEB with further weaker associations for previous age and HbA1c. CONCLUSIONS: Our results contribute to better understanding the course of DEB in patients with early-onset diabetes and emphasize the relevance of regular DEB screenings including the age group of young adults.