Factors associated with diabetic foot ulcers and lower limb amputations in type 1 and type 2 diabetes supported by real-world data from the German/Austrian DPV registry.

AIMS: Diabetic foot ulcer (DFU) is a leading cause of lower limb amputations in people with diabetes. This study was aimed to retrospectively analyze factors affecting DFU using real-world data from a large, prospective central-European diabetes registry (DPV [Diabetes-Patienten-Verlaufsdokumentation]). MATERIALS AND METHODS: We matched adults with type 1 (T1D) or type 2 diabetes (T2D) and DFU to controls without DFU by diabetes type, age, sex, diabetes duration, and treatment year to compare possible risk factors. Cox regression was used to calculate hazard ratios for amputation among those with DFU. RESULTS: In our cohort (N = 63 464), male sex, taller height, and diabetes complications such as neuropathy, peripheral artery disease, nephropathy, and retinopathy were associated with DFU (all p < .001). Glycated hemoglobin (HbA1c) was related to DFU only in T1D (mean with 95% confidence interval [CI]: 7.8 [6.9-9.0] % vs 7.5 [6.8-8.5] %, p < .001). High triglycerides and worse low-density lipoprotein/high-density lipoprotein ratio were also associated with DFU in T1D, whereas smoking (14.7% vs 13.1%) and alcohol abuse (6.4% vs 3.8%, both p < .001) were associated with DFU in T2D. Male sex, higher Wagner grades, and high HbA1c in both diabetes types and insulin use in T2D were associated with increased hazard ratios for amputations. CONCLUSIONS: Sex, body height, and diabetes complications were associated DFU risk in adults with T1D and T2D. Improvement in glycemic control and lipid levels in T1D and reduction of smoking and drinking in T2D may be appropriate interventions to reduce the risk for DFU or amputations.

Distribution and determinants of glycosylated hemoglobin in adolescents - Results from a nationwide population-based survey in Germany.

The role of glycosylated hemoglobin (HbA1c) in youth is largely unclear. The aims of this study are to investigate the distribution and potential determinants of HbA1c among a population-based sample of adolescents. The German Health Interview and Examination Survey for Children and Adolescents (KiGGS) Wave 2 includes a nationwide representative sample of 0-17-year-old participants. For this evaluation, data from a randomly selected subgroup aged 14-17 years and without diagnosed diabetes was included (n = 857). Percentile-based HbA1c values (measured at laboratory in whole blood samples by high performance liquid chromatography) were calculated to examine HbA1c distribution. Multivariable linear regression analyses were performed to investigate factors (age, sex, parental socioeconomic status, body mass index (BMI), birth weight, smoking, alcohol consumption, healthy food diversity, sport activity, oral contraceptive use) associated with HbA1c. The mean HbA1c level was 5.2% (minimum: 3.9%, P10: 4.8%, P50: 5.1%, P90: 5.5%, maximum: 6.7%). Overall, 2.8% of adolescents had an HbA1c value in the prediabetic range (5.7-6.4%) and 0.1% had an undiagnosed diabetes (≥6.5%). Multivariable regression analysis showed an inverse association of age with HbA1c (17 vs. 14 years: ß: -1.18; 95% CI -2.05, -0.31). Higher HbA1c values were observed for higher BMI-standard deviation scores (SDS) (ß: 0.24; 95% CI -0.04, 0.52) and smoking (ß: 0.73; 95% CI -0.12, 1.57), but these tendencies were non-significant. In sex-stratified analysis, smoking and birth weight were significantly associated with HbA1c in boys. Among adolescents without diagnosed diabetes in Germany, HbA1c values ranged from 3.9% to 6.7%. To ensure health in adulthood, the influence of determinants on HbA1c levels in younger age should be further investigated.

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.

Twelve-Month Outcomes after Metabolic and Bariatric Surgery among Youths Participating in a Structured Preparation and Follow-Up Program: Results of the Youth with Extreme Obesity Study.

INTRODUCTION: While invasive and associated with risks, metabolic and bariatric surgery (MBS) can promote sustained weight loss and substantial health benefits in youths with extreme obesity. The path toward informed decision making for or against MBS is poorly characterized and postoperative follow-up to assess risks and benefits is inconsistent. In youths with extreme obesity, we aimed to evaluate decision making toward MBS, as well as MBS outcomes and adherence with follow-up and recommendations in the setting of a structured pre- and post-MBS program. METHODS: Participants were recruited in the setting of the multicenter "Youth with Extreme Obesity Study" (YES). YES is a cohort study in adolescents and young adults aged 14-24 years with obesity (BMI ≥30.0 kg/m2) who were recruited at four medical centers and one job center in Germany between 2012 and 2018. Participants at two medical centers with BMI ≥35 kg/m2, aged 14-24 years, and interested in pursuing MBS were included in the subproject 3 "Safety and effectiveness of weight loss surgery in adolescents with severe obesity within a structured pre- and post-surgery treatment program - an observational study" that comprised a 2-months pre- and 12-months post-MBS program. RESULTS: Twenty-eight of 169 youths (17%) with BMI ≥35 kg/m2 were interested in MBS. Twenty-six fulfilled published eligibility criteria for MBS and participated in the structured pre-MBS preparation program. Of these, 9 participants (2 females) decided against, and 17 (n = 11 females) decided for MBS (sleeve gastrectomy). The 12-month follow-up rate was high (16/17 [94%]) and all participants achieved significant weight reduction (ΔBMI: -16.1 ± 5.6 kg/m2). Eleven of 16 participants (69%) reported taking the prescribed dietary supplements in the first year after MBS, but only five of them (31%) did so daily. In contrast to the high 12-month retention rate, follow-up after completion of the structured program was low at 24-months (9/16 [56%]) and at 36-months (5/15 [36%]), respectively. CONCLUSION: Participants demonstrated active decision making for or against MBS and high adherence with the structured pre- and 12 months post-MBS program, but participation was low thereafter. These findings endorse the need for longer term structured post-MBS programs to capture long-term outcomes and provide adequate care in this vulnerable group at the transition to adulthood.

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.

An analysis of DPV and DIVE registry patients with chronic kidney disease according to the finerenone phase III clinical trial selection criteria.

BACKGROUND: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany. METHODS: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 OR eGFR ≥ 60 mL/min/1.73m2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared. RESULTS: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible. CONCLUSIONS: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted.

Changes in cardiovascular risk factors among children and young adults with type 1 diabetes during the COVID-19 pandemic compared to previous years-Results from the German DPV registry.

BACKGROUND: The diverse stages of the COVID-19 pandemic led to several social circumstances that influenced daily life and health behavior. PURPOSE: To evaluate changes in cardiovascular risk factors and physical activity among children and young adults with type 1 diabetes (T1D) during the COVID-19 pandemic in Germany compared to previous years. METHODS: A total of 32 785 individuals aged 6-21 years at baseline with T1D from the German diabetes patient follow-up (DPV) registry contributed data on 101 484 person-years between 2016 and 2021. The first treatment year of each individual within this period was considered as baseline. Based on trends from 2016 to 2019, we estimated differences in body mass index-SD score (BMI-SDS), blood pressure (BP-SDS), and lipid levels (non-high-density lipoprotein [non-HDL]) between observed and predicted estimates for the years 2020 and 2021 using linear regression analysis standardized for age, diabetes duration, sex, and migratory background. The proportion doing organized sports and smoking cigarettes was analyzed using multivariable logistic regression models. RESULTS: BMI-SDS increased constantly from 2016 to 2021 without a significant increase above expected values for 2020/2021. Systolic BP-SDS (difference observed vs. expected with 95% confidence interval, 2020: 0.10 [0.07-0.14], 2021: 0.17 [0.14-0.20]) and non-HDL (2020: 2.7 [1.3-4.1] mg/dl, 2021: 4.1 [2.7-5.5] mg/dl) were significantly increased (all p < .001) in both pandemic years. The proportion of subjects participating in organized sports was reduced from over 70% in prepandemic years to 35%-65% in diverse stages/waves of the COVID-19 pandemic. The percentage smoking cigarettes did not change. CONCLUSIONS: We describe an increase in BP and atherogenic lipid levels coinciding with a reduction in physical activity but no acceleration of the prepandemic increases in BMI-SDS among young people with T1D during the COVID-19 pandemic.

Validation of a risk prediction model for early chronic kidney disease in patients with type 2 diabetes: Data from the German/Austrian Diabetes Prospective Follow-up registry.

AIM: To validate a recently proposed risk prediction model for chronic kidney disease (CKD) in type 2 diabetes (T2D). MATERIALS AND METHODS: Subjects from the German/Austrian Diabetes Prospective Follow-up (DPV) registry with T2D, normoalbuminuria, an estimated glomerular filtration rate of 60 ml/min/1.73m2 or higher and aged 39-75 years were included. Prognostic factors included age, body mass index (BMI), smoking status and HbA1c. Subjects were categorized into low, moderate, high and very high-risk groups. Outcome was CKD occurrence. RESULTS: Subjects (n = 10 922) had a mean age of 61 years, diabetes duration of 6 years, BMI of 31.7 kg/m2 , HbA1c of 6.9% (52 mmol/mol); 9.1% had diabetic retinopathy and 16.3% were smokers. After the follow-up (~59 months), 37.4% subjects developed CKD. The area under the curve (AUC; unadjusted base model) was 0.58 (95% CI 0.57-0.59). After adjustment for diabetes and follow-up duration, the AUC was 0.69 (95% CI 0.68-0.70), indicating improved discrimination. After follow-up, 15.0%, 20.1%, 27.7% and 40.2% patients in the low, moderate, high and very high-risk groups, respectively, had developed CKD. Increasing risk score correlated with increasing cumulative risk of incident CKD over a median of 4.5 years of follow-up (P < .0001). CONCLUSIONS: The predictive model achieved moderate discrimination but good calibration in a German/Austrian T2D population, suggesting that the model may be relevant for determining CKD risk.

Differences in retinopathy prevalence and associated risk factors across 11 countries in three continents: A cross-sectional study of 156,090 children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). SUBJECTS AND METHODS: Data on individuals aged 10-21 years with T1D for >1 year during the period 2000-2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. RESULTS: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper-1-year-increase  = 1.04, 95% CI: 1.03-1.04, p < 0.0001), and decreased over time (aORper-1-year-increase  = 0.99, 95% CI: 0.98-1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper-1-mmol/mol-increase-in-HbA1c  = 1.03, 95% CI: 1.03-1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11-1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17-1.44, p < 0.0001). CONCLUSIONS: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking.

A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.

BACKGROUND: Diabetes in childhood and adolescence includes autoimmune and non-autoimmune forms with heterogeneity in clinical and biochemical presentations. An unresolved question is whether there are subtypes, endotypes, or theratypes within these forms of diabetes. METHODS: The multivariable classification and regression tree (CART) analysis method was used to identify subgroups of diabetes with differing residual C-peptide levels in patients with newly diagnosed diabetes before 20 years of age (n=1192). The robustness of the model was assessed in a confirmation and prognosis cohort (n=2722). FINDINGS: The analysis selected age, haemoglobin A1c (HbA1c), and body mass index (BMI) as split parameters that classified patients into seven islet autoantibody-positive and three autoantibody-negative groups. There were substantial differences in genetics, inflammatory markers, diabetes family history, lipids, 25-OH-Vitamin D3, insulin treatment, insulin sensitivity and insulin autoimmunity among the groups, and the method stratified patients with potentially different pathogeneses and prognoses. Interferon-É£ and/or tumour necrosis factor inflammatory signatures were enriched in the youngest islet autoantibody-positive groups and in patients with the lowest C-peptide values, while higher BMI and type 2 diabetes characteristics were found in older patients. The prognostic relevance was demonstrated by persistent differences in HbA1c at 7 years median follow-up. INTERPRETATION: This multivariable analysis revealed subgroups of young patients with diabetes that have potential pathogenetic and therapeutic relevance. FUNDING: The work was supported by funds from the German Federal Ministry of Education and Research (01KX1818; FKZ 01GI0805; DZD e.V.), the Innovative Medicine Initiative 2 Joint Undertaking INNODIA (grant agreement No. 115797), the German Robert Koch Institute, and the German Diabetes Association.

Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes.

AIM: Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed. METHODS: This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis. RESULTS: Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period. CONCLUSIONS: Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

Renal Complications and Duration of Diabetes: An International Comparison in Persons with Type 1 Diabetes.

INTRODUCTION: Renal complications are both a marker of previous suboptimal glycaemic control and a major risk factor for cardiovascular disease in persons with type 1 diabetes (T1D). The aim of the study was to evaluate the prevalence of renal complications in persons with T1D in four geographical regions. METHODS: Nationwide registry data from Austria/Germany, Sweden and the US were used to estimate the prevalence of renal complications from January 2016 until September 2018. Chronic kidney disease (CKD) and albuminuria in the study population and each registry were analysed by diabetes duration. Risk factors for renal complications were described by registry. RESULTS: In the total cohort of 78.926 adults with T1D, mean age was 44.4 ± 18.43 years and mean diabetes duration was 21.6 ± 22 years. Mean estimated glomerular filtration rate (eGFR) was 94.0 ± 31.45 ml/min, 13.0% had microalbuminuria and 3.9% had macroalbuminuria. Mean age, diabetes duration, use of insulin pumps and continuous glucose monitoring, as well as presence of albuminuria, varied between registries. Albuminuria was present in approximately 10% of persons with diabetes duration < 20 years and impaired renal function (eGFR < 60 ml/min) was present in 17%. In persons with diabetes duration > 40 years, approximately one-third had albuminuria and 25% had impaired renal function. CONCLUSIONS: This analysis used three nationwide registries of persons with T1D. Despite recent use of more effective diabetes therapies, a substantial proportion of persons with T1D have renal complications at < 20 years after diagnosis. Efficient glucose-lowering and renal-protective strategies are needed in persons with T1D.

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.

Bone Fractures in Children and Young Adults With Type 1 Diabetes: Age Distribution, Fracture Location, and the Role of Glycemic Control.

Type 1 diabetes (T1D) is a known risk factor for fractures, but the underlying pathophysiology is still not fully understood. This study aims to define age peaks and frequent fracture sites of children and young adults with T1D. Additionally, associations of fractures with metabolic and lifestyle factors as well as with additional complications in individuals with T1D were analyzed. A total of 750 individuals with T1D aged ≤25 years with fractures were matched to 3750 patients with T1D without fractures by demographics and insulin regimen. Hemoglobin A1c (HbA1c) values were compared using linear regression, and logistic regression was used to calculate odds ratios (OR) for fractures in individuals with acute complications and diseases. Median (Q1-Q3) age was 12.7 (9.9 to 14.9) years in individuals with fractures and 16.3 (12.6 to 17.8) years in the entire control group with 65% versus 53% males. Peak age for fractures was 7 to <15 years in males and 9 to <11 years in females, which is earlier than reported for the general population. HbA1c (%) was significantly higher in individuals with fractures than in controls (difference of estimated means: 0.26%; 95% confidence interval [CI] 0.07-0.46), especially in postpubertal females (0.68; 0.10-1.26). Significantly higher odds for fractures were observed in individuals with severe hypoglycemia (OR = 1.90; 95% CI 1.47-2.47), especially in prepubertal females (OR = 2.81; 1.21-6.52]) and postpubertal males (2.44; 1.11-5.38), celiac disease (2.02; 1.67-2.45), and with a history of smoking (1.38; 1.02-1.88). The age peak of fractures seems to be earlier in T1D than in the general population. Poor glycemic control is related to fractures, even before puberty. Associations of HbA1c and severe hypoglycemia with fractures highly depend on age and sex. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Immune-checkpoint inhibitor-associated diabetes compared to other diabetes types - A prospective, matched control study.

BACKGROUND: To describe checkpoint inhibitor-induced diabetes mellitus (CPI-DM) and to compare with regular type 1 (T1DM), type 2 (T2DM), and medication-induced diabetes mellitus (MI-DM). METHODS: We included 88 177 adult patients from the Diabetes Patient Follow-Up (DPV) registry with diabetes manifestation between 2011 and 2020. Inclusion criteria were T1DM, T2DM, MI-DM, or CPI-DM. Because of the heterogeneity between the groups, we matched patients by age, sex, and diabetes duration using propensity scores. Patient data were aggregated in the respective first documented treatment year. RESULTS: The matched cohort consisted of 24 164 patients; T1DM: 29, T2DM: 24000, MI-DM: 120, CPI-DM: 15 patients. Median age at manifestation of CPI-DM patients was 63.6 (57.2-72.8) years (53.3% male). Body mass index in CPI-DM patients was significantly lower (26.8 [23.9-28.1] kg/m2 ) compared with T2DM patients (29.8 [26.2-34.3] kg/m2 , P = 0.02). At manifestation, HbA1c was significantly higher in CPI-DM compared with MI-DM, but there was no difference during follow-up. Diabetic ketoacidosis (DKA) was documented in six CPI-DM patients (T1DM: 0%, T2DM: 0.4%, MI-DM: 0.0%). Fourteen CPI-DM patients were treated with insulin, and three received additional oral antidiabetics. The most common therapy in T2DM was lifestyle modification (38.8%), insulin in MI-DM (52.5%). Concomitant autoimmune thyroid disease was present in four CPI-DM patients (T1DM: 0.0%, T2DM: 1.0%, MI-DM: 0.8%). CONCLUSIONS: The data from this controlled study show that CPI-DM is characterized by a high prevalence of DKA, autoimmune comorbidity, and metabolic decompensation at onset. Structured diagnostic monitoring is warranted to prevent DKA and other acute endocrine complications in CPI-treated patients.

Comparison of cardiovascular risk factors between children and adolescents with classes III and IV obesity: findings from the APV cohort.

OBJECTIVE: Obesity is associated with many cardiovascular risk factors (CVRF) in childhood. There is an ongoing discussion whether there is a linear relationship between degree of overweight and deterioration of CVRFs justifying body mass index (BMI) cut-offs for treatment decisions. METHODS: We studied the impact of BMI-SDS on blood pressure, lipids, and glucose metabolism in 76,660 children (aged 5-25 years) subdivided in five groups: overweight (BMI-SDS 1.3 to <1.8), obesity class I (BMI-SDS 1.8 to <2.3), class II (BMI-SDS 2.3-2.8), class III (BMI-SDS > 2.8-3.3), and class IV (BMI-SDS > 3.3). Analyses were stratified by age and sex. RESULTS: We found a relationship between BMI-SDS and blood pressure, triglycerides, HDL cholesterol, liver enzymes, and the triglycerides-HDL-cholesterol ratio at any age and sex. Many of these associations lost significance when comparing children with obesity classes III and IV: In females < 14 years and males < 12 years triglycerides and glucose parameters did not differ significantly between classes IV and III obesity. Prevalence of dyslipidemia was significantly higher in class IV compared to class III obesity only in females ≥ 14 years and males ≥ 12 years but not in younger children. In girls < 14 years and in boys of any age, the prevalences of type 2 diabetes mellitus did not differ between classes III and IV obesity. CONCLUSIONS: Since a BMI above the highest BMI cut-off was not associated consistently with dyslipidemia and disturbed glucose metabolism in every age group both in boys and girls, measurements of CVRFs instead of BMI cut-off seem preferable to guide different treatment approaches in obesity such as medications or bariatric surgery.

Involving patients' perspective in the development of an internet- and mobile-based CBT intervention for adolescents with chronic medical conditions: Findings from a qualitative study.

OBJECTIVE: A user-centered approach is critical for increasing the adherence to and effectiveness of an internet- and mobile-based intervention program. Therefore, potential future intervention users were involved in the development of an internet- and mobile-based cognitive behavioral therapy program (iCBT) for adolescents and young adults (AYA) with chronic medical conditions and comorbid symptoms of anxiety or depression. We aimed to identify challenges and coping strategies of the intended target group, as well as their needs and preferred intervention characteristics for an iCBT program. METHODS: Twenty AYA (aged 14-20, 60% females) with either type 1 diabetes (55%), juvenile idiopathic arthritis (25%) or cystic fibrosis (20%) were interviewed in condition-specific focus groups (4-11 participants per group) either via videoconferencing or face-to-face. Transcript verbatim data was analyzed using content analysis. RESULTS: Frequently reported disease-specific burdens were among others fear of disease progression, non-acceptance of disease and stressful incidents related to and aversions against medical therapy. Most frequently reported coping strategies included, seeking social support and accepting the disease. Recommendations for the content of an iCBT for comorbid symptoms of anxiety and depression comprised: dealing with disease-related fears and getting advice on health-promoting lifestyles. iCBT characteristics considered preferable by participants were: providing individual feedback by a real-person; implementation of a feature to monitor treatment progress; youthful and varied content presentation; time per session not exceeding 1 h; non-involvement of parents. A mobile-based reminder feature was considered useful, and individual tailoring and self-determination of iCBT content was considered desirable. CONCLUSIONS: The findings highlight important patient perspectives and age-specific recommendations which can help design more optimal iCBT interventions for AYA with chronic medical conditions.

Transition from gynaecomastia to lipomastia in pubertal boys.

OBJECTIVE: Gynaecomastia is frequent in pubertal boys and is regarded as a self-limiting abnormality. However, longitudinal studies proving this hypothesis are scarce. DESIGN: Longitudinal follow-up study (median 2.4, range 1.0-4.8 years). METHODS: The regression of breast diameter was analysed in 31 pubertal boys aged 11.7-16.1 (median 13.2) years with gynaecomastia. Furthermore, weight changes (as BMI-SDS) and pubertal stage, oestradiol [E2], oestriol, oestrone, androstenedione, testosterone [T], dihydrotestosterone, gonadotropins, IGF-1, and IGFBP-3 serum concentrations determined at first clinical presentation were related to breast diameter regression determined by palpation and disappearance of breast glandular tissue in ultrasound in follow-up to identify possible predictors of breast regression. RESULTS: During the observation period, the breast diameter decreased (in median -1 (interquartile range [IQR] -5 to +1) cm). At follow-up, 6% of boys had no breast enlargement any more, and 65% developed lipomastia. Gynaecomastia was still present in 29%. None of the analysed hormones was related significantly to breast diameter regression or disappearance of breast glandular tissue. In multiple linear regression analyses adjusted for observational period, as well as age and BMI-SDS at first presentation, changes in BMI-SDS (ß-coefficient 6.0 ± 2.3, p = .015) but not the E2/T ratio or any other hormone determined at baseline was related to changes in breast diameter. CONCLUSIONS: Breast diameter regression seems not to be predictable by a hormone profile in pubertal boys with gynaecomastia. In pubertal boys presenting with gynaecomastia, conversion to lipomastia of smaller volume is common. The reduction of weight status was the best predictor of breast diameter regression.

Type 2 diabetes in older patients: an analysis of the DPV and DIVE databases.

BACKGROUND: The clinical profile differs between old and young patients with type 2 diabetes mellitus (T2DM). We explored, based on a large real-world database, patient and disease characteristics and actual treatment patterns by age. METHODS: The analysis was based on the DIVE and DPV registries of patients with T2DM. Patients were analyzed by age groups 50-59 (middle-young), 60-69 (young-old), 70-79 (middle-old), 80-89 (old), and 90 years or more (oldest-old). RESULTS: A total of 396,719 patients were analyzed, of which 17.7% were 50-59 years, 27.7% 60-69 years, 34.3% 70-79 years, 18.3% 80-89 years and 2.0% at least 90 years. We found that (a) T2DM in old and oldest-old patients was characterized much less by the presence of metabolic risk factors such as hypertension, obesity, dyslipidemia and smoking than in younger patients; (b) the HbA1c was much lower in oldest-old than in middle-young patients (7.2 ± 1.6% versus 8.0 ± 2.2%; p < 0.001), but it was associated with higher proportions of patients with severe hypoglycemia (7.0 versus 1.6%; p < 0.001); (c) this was potentially associated with the higher and increasing rates of insulin use in older patients (from 17.6% to 37.6%, p < 0.001) and the particular comorbidity profile of these patients, for example, chronic kidney disease (CKD); (d) patients with late diabetes onset had lower HbA1c values, lower bodyweight and less cardiovascular risk factors; (e) patients with a longer diabetes duration had a considerable increase in macrovascular and even more microvascular complications. CONCLUSION: In very old patients there is a need for frequent careful routine assessment and a tailored pharmacotherapy in which patient safety is much more important than blood-glucose-lowering efficacy.

Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database.

BACKGROUND: Wolcott-Rallison syndrome (WRS) is characterized by permanent early-onset diabetes, skeletal dysplasia and several additional features, e.g. recurrent liver failure. This is the first multicentre approach that focuses on diabetes management in WRS. We searched the German/Austrian Diabetes-Patienten-Verlaufsdokumentation (DPV) registry and studied anthropometric characteristics, diabetes treatment, glycaemic control and occurrence of severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in 11 patients with WRS. Furthermore, all local treatment centres were personally contacted to retrieve additional information on genetic characteristics, migration background and rate of consanguinity. RESULTS: Data were analysed at diabetes onset and after a median follow-up period of 3 (1.5-9.0) years (time from diagnosis to latest follow-up). Median age at diabetes onset was 0.2 (0.1-0.3) years, while onset was delayed in one patient (aged 16 months). Seventy percent of patients manifested with DKA. At follow-up, 90% of patients were on insulin pump therapy requiring 0.7 [0.5-1.0] IU of insulin/kg/d. More than two third of patients had HbA1c level ≥ 8%, 40% experienced at least one episode of SH in the course of the disease. Three patients died at 0.6, 5 and 9 years of age, respectively. To the best of our knowledge three patients carried novel mutations in EIF2AK3. CONCLUSION: Insulin requirements of individuals with WRS registered in DPV appear to be comparable to those of preschool children with well-controlled type 1 diabetes, while glycaemic control tends to be worse and episodes of SH tend to be more common. The majority of individuals with WRS in the DPV registry does not reach glycaemic target for HbA1c as defined for preschool children (< 7.5%). International multicentre studies are required to further improve our knowledge on the care of children with WRS.