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To study diabetic cataract in type 1 diabetes in a large pediatric cohort.The 92,633 patients aged 0.5-21 years from German/Austrian multicenter diabetes registry (DPV) were analyzed. The 235 patients (0.25%) with diabetic cataract were found, 200 could be categorized: 67 with early cataract (3 months before diabetes onset - 12 months afterwards), 133 with late cataract (12 months after diabetes onset). Regression models adjusted for age and gender were used to compare clinical parameters at diabetes onset. Regression models for patients with late cataract were implemented for the total documentation period and additionally adjusted for diabetes duration.Rate of cataract development shows a peak at diabetes onset and declines with longer diabetes duration. Patients with cataract showed strong female preponderance. Patients developing early cataract were older at diabetes onset (12.8 years [11.8/13.9] vs. 8.9 [8.9/9.0]; p 0.001) and showed higher HbA1c than patients without cataract (9.0% [8.55/9.38] vs. 7.6% [7.60/7.61]; p 0.001). They had lower height-SDS, (-0.22 [-0.48/0.04] vs. 0.25 [0.24/0.26]; p 0.001), lower weight-SDS (-0.31 [-0.55/-0.08] vs. 0.21 [0.20/0.21]; p 0.001) and lower BMI-SDS (-0.25 [-0.49/-0.02] vs. 0.12 [0.12/0.13); p = 0.002). Patients with late cataract showed higher HbA1c at diabetes onset (8.35% [8.08/8.62] vs. 8.04% [8.03/8.05]; p = 0.023) and higher mean HbA1c during total documentation period (8.00% [7.62/8.34] vs. 7.62% [7.61/7.63]; p = 0.048).Our data confirm known demographic and clinical characteristics of patients developing early cataract. Hyperglycemia-induced osmotic damage to lens fibers at diabetes onset might be the main pathomechanism. Long term glycemic control is associated with cataract development.

OBJECTIVE To investigate the occupational and financial consequences for parents following the onset of type 1 diabetes in their child. RESEARCH DESIGN AND METHODS A questionnaire assessing occupational and financial situations before and in the first year after the onset of diabetes was distributed to all families with a child ≤14 years of age at diagnosis with a diabetes duration of at least 12 months in nine German pediatric diabetes centers. RESULTS Data of 1,144 children (mean age at diagnosis 6.7 [3.6] years; 46.5% female) and their families were obtained. Mothers’ occupational status reflected in paid working hours was significantly reduced in the first year after their child's diabetes diagnosis (P < 0.001). Overall, 15.1% of mothers stopped working, and 11.5% reduced working hours. Mothers of preschool children were particularly affected. Fathers’ working status hardly changed (P = 0.75). Nearly half of the families (46.4%) reported moderate to severe financial losses. Compared with an earlier similar study in 2003, significant negative occupational consequences for mothers and financial burden on families remained unchanged in 2018 (P = 0.59 and 0.31, respectively). CONCLUSIONS Mothers of young children with newly diagnosed diabetes experienced negative consequences in their occupational situation. This inequality for mothers can have long-term negative consequences for their mental health and future economic situation. There is an urgent need for action to reduce the burden on families and to provide professional, social, and regulatory support, especially for mothers of young children with diabetes.

Background: Despite increasing use of technology in type 1 diabetes, persistent ethnic and socio-economic disparities have been reported. We analyzed how the use of insulin pump therapy and continuous glucose monitoring (CGM) evolved over the years in Germany depending on demographics and area deprivation. Method: We investigated the use of insulin pump and CGM between 2016 and 2019 in 37,798 patients with type 1 diabetes aged Results: Between 2016 and 2019, the regional distribution of insulin pump use did not change substantially and the association with area deprivation remained non-linear and statistically non-significant. The effect of area deprivation on CGM use decreased continuously and disappeared in 2019 (OR [95%-CI] Q1 vs Q5: 1.85 [1.63-2.10] in 2016; 0.97 [0.88-1.08] in 2019). The effect of migration background on the use of either technology decreased over the years but remained significant in 2019. Girls had constantly higher odds of using an insulin pump than boys (OR: 1.25 [1.18-1.31] in 2019), whereas no gender difference was identified for CGM use. Conclusions: Although disparities decreased in Germany, access to diabetes technology still depends on migration background in 2019, and gender differences in pump use persist. As technological advances are made, further research is needed to understand the reasons for these persistent disparities.

OBJECTIVE To investigate temporal trends and contemporary use of insulin pump therapy and glucose monitoring in type 1 diabetes. RESEARCH DESIGN AND METHODS In a population-based study, we analyzed the use of insulin pump therapy, continuous glucose monitoring (CGM), and self-monitoring of blood glucose (SMBG) from 1995 to 2017 in patients with type 1 diabetes identified from the Diabetes Prospective Follow-up (DPV) database in Germany and Austria. Patients were stratified by age, sex, migration background, and country. RESULTS Among 96,547 patients with type 1 diabetes (median age 17.9 years, 53% males), the percentage using insulin pump therapy increased from 1% in 1995 to 53% in 2017, with the highest rates in the youngest patients (92% in preschoolers, 74% in children, 56% in adolescents aged CONCLUSIONS Since 1995, insulin pump use has continuously increased, and insulin pump therapy is now standard in patients aged

Pediatric rheumatology 19(1), 38 (2021). doi:10.1186/s12969-021-00510-8, Published by BioMed Central, London

BACKGROUND To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry). METHODS Registry participants aged

Background Canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) older than 2 years. Objectives The aim of the German Biologics Registry (BiKeR) is the surveillance of JIA patients exposed to biologics. Methods Baseline demographics and disease activity parameters were documented. Efficacy was determined using the JADAS and the proposed criteria for inactive disease on medication. Safety assessments were based on reports of adverse events (AE). All reports have been coded according to MedDRA ®. Results 48 sJIA patients with 82.5 patient-years (PY) of exposure to Canakinumab were recorded in the German BiKeR registry. The total observation time (from date of first dose until last follow-up, censored, if another biologic was started) was calculated with 109.9 PY. The cohort treated with Canakinumab had experienced long disease duration of 2.9+/-3.8 years (mean +/- SD). 21 (44%) were pre-treated with methotrexate, 10 (21%) with Etanercept, 3 (6%) with Adalimumab, 18 (38%) with Anakinra and 19 (40%) with Tocilizumab. Concomitantly, 9 (18.8%) received methotrexate, 22 (45.8%) NSAIDs and 23 (48%) systemic corticosteroids. At last follow up upon treatment, 48%/44%/42%/38% of patients reached PedACR30/50/70/90 improvement. 8 patients (16.7%) had inactive disease according to the Wallace criteria. The median (IQR1-IQR3) JADAS10 score decreased from 12.6 (6.2-15.8) at baseline to 0.5 (0.0-2.8). During ongoing treatment, approximately 82% of patients achieved a JADAS defined minimal disease activity; while 64% reached a JADAS defined remission at last follow-up. 125 adverse events (AE) were recorded (114 events/100PY [95% CI 96-136]). Of these, 22 qualified as serious adverse events (SAE) (20/100PY [13-30]). 100 AEs were observed during exposure or up to 90 days follow up after the last exposure to Canakinumab (121/100PY [99-147]). 19 qualified as SAE (23/100PY [15-36]). Adverse Events of Special Interest were serious and medically important infection (n=4), cytopenia (n=4), macrophage activation syndrome (n=3). There was no opportunistic infection, intestinal perforation, anaphylaxis or other hypersensitivity, thrombotic event, evolving autoimmune disease, cardiac or cerebral event, bleeding, malignancy, or death. A total of 38 patients (79%) discontinued treatment, 8 (17%) due to lack or efficacy, 16 (33%) due to remission and 2 (4%) because of intolerance. Conclusion The current analysis adds to the established safety profile of Canakinumab and demonstrates that safety was comparable and consistent with the overall AE profile of Canakinumab in paediatric patients. MAS occurred in three sJIA patients and might be a JIA-associated feature. Infections were the most frequent AE, but only two serious infections were reported. No new safety signals specific to the paediatric population were identified for Canakinumab; the risk profile of Canakinumab remains positive for the approved paediatric indication sJIA. References [1] Horneff G, Klein A, Klotsche J, Minden K, Huppertz HI, Weller-Heinemann F, Kuemmerle-Deschner J, Haas JP, Hospach A. Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab. Arthritis Res Ther. 2016Nov24;18(1):272 Acknowledgement The authors acknowledge all contributors to BIKER, patients, parents and study staff Disclosure of Interests Gerd Horneff: None declared, Eggert Lilienthal: None declared, Ralf Trauzeddel: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Frank Dressler Paid instructor for: Abbvie, Pfizer, Novartis, Michaela Sailer-Hoeck: None declared, Gerd Ganser: None declared, Frank Weller-Heinemann: None declared, Georg Heubner: None declared, Andreas Urban: None declared, Michael Ruhlmann: None declared, Christoph Rietschel: None declared, Markus Hufnagel: None declared, Wolfgang Emminger: None declared, Ariane Klein: None declared

Background Anakinra (ANA) is recommended for treatment of systemic juvenile idiopathic arthritis (sJIA) and has recently received EMA approval. Objectives To describe safety and effectiveness of ANA in clinical practice in sJIA patients documented in the German Biologics registry (BiKeR). Methods Demographic and clinical parameters of the patients were recorded at BiKeR enrollment, ANA effectiveness was evaluated by half-yearly evaluation of disease activity using JADAS-10. Safety assessments were based on MedDRA-coded adverse events (AE) reports. Results Until December 1 2018, 50 sJIA patients treated with ANA were registered, representing 113.4 patient-years (PY) of observation, with 10 patients (20%) receiving ANA for at least 4 years. The cohort treated with ANA had experienced a prior disease duration of 3.5+/-3.8 years (mean+/-SD). Most sJIA patients treated with ANA received pretreatment: 35 patients (70%) were pretreated with at least one other biologic, mostly etanercept (n=28), followed by tocilizumab (6) and canakinumab (1). Further pretreatments included methotrexate (MTX, n= 35), ciclosporine A (n=13), azathioprine (n=8) and other DMARDs at lower frequency. 39 patients had received corticosteroids. Concomitant treatment consisted of NSAIDs (n=20), systemic steroids (n=35), MTX (n=29) and other DMARDs (n=8). At month 3, JADAS minimal disease activity (MDA)/JADAS remission and inactive disease according to Wallace [1] were observed in 42%/37%and 47%, respectively. After one year of treatment, the rates were 62%/45% and 56%, respectively (Figure 1). Conclusion The current analysis adds to the established safety profile of Anakinra and demonstrates that in ANA treated patients with sJIA the rate of SAEs was comparable and consistent with the overall AE profile of ANA in pediatric patients. Hospitalisation was the usual reason for classification as serious AE. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients. Disclosure of Interests Ariane Klein: None declared, Veronika Ntam Atemnkeng: None declared, Frank Dressler Paid instructor for: Abbvie, Pfizer, Novartis, Ivan Foeldvari Consultant for: Chugai, Novartis, Rolf Michael Kuster: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Gerd Ganser: None declared, Kirsten Minden Consultant for: AbbVie, Dirk Foell Grant/research support from: not specified, Consultant for: not specified, Speakers bureau: not specified, Frank Weller-Heinemann: None declared, Jasmin Kuemmerle-Deschner Grant/research support from: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Consultant for: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Speakers bureau: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Boris Huegle: None declared, Christoph Rietschel: None declared, Eggert Lilienthal: None declared, Gerd Horneff: None declared

OBJECTIVE Research on β-cell autoimmunity in cystic fibrosis (CF)–related diabetes (CFRD) is still rare. We aimed to analyze the frequency of β-cell autoimmunity and the influence on age at diabetes onset, insulin requirement, type of insulin therapy, and hypoglycemic or ketoacidotic events in patients with CFRD compared with antibody-negative patients with CFRD in the Diabetes Patienten Verlaufsdokumentation (DPV) registry. RESEARCH DESIGN AND METHODS We analyzed data of 837 patients with CFRD in the German/Austrian DPV database by multivariable mixed-regression modeling. RESULTS In our cohort, 8.5% of patients with CFRD (n = 72) were found to be β-cell antibody positive. There was a female preponderance in this patient group: 65.3 vs. 57.6%. Diabetes onset (median [interquartile range]) was earlier (14.00 [10.15–15.90] vs. 16.10 [13.50–21.20] years; P < 0.005), and insulin dose/kg body weight was higher (0.95 [0.61–1.15] vs. 0.67 [0.33–1.04] IU/kg; P < 0.05). There were also differences in the type of insulin treatment. Insulin pump therapy was used significantly more often in patients with CFRD with β-cell autoimmunity (18.2 vs. 6.4%; P < 0.05). The differences for multiple daily injections (ICT) and conventional therapy (CT) were not significant (ICT: 67.7 vs. 79.0%; CT: 15.2 vs. 14.6). Oral antidiabetic agents were rarely used in both groups. Rate of severe hypoglycemia with coma and rate of ketoacidosis were higher in antibody-positive patients (hypoglycemia with coma: 8.0 vs. 1.4, P < 0.05; ketoacidosis: 9.3 vs. 0.9, P < 0.05). CONCLUSIONS Presence of β-cell autoantibodies in our cohort of patients with CFRD (8.5%) appeared to be greater than in the general population and was associated with female sex, earlier onset of diabetes, and higher insulin requirement. Insulin pump therapy was used significantly more often in patients with β-cell antibodies. Severe hypoglycemia and ketoacidosis were significantly more frequent in CFRD with β-cell autoimmunity compared with β-cell antibody-negative patients with CFRD.

Background Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. Methods In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) (https://aid-register.de). Data for this retrospective TCZ study were documented by 13 centers. Results From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1–18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. Conclusion Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. Trial registration The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Adult subjects with growth hormone (GH) deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. In adults, these events are associated with elevated circulating concentrations of asymmetric dimethylarginine (ADMA) which is an endogenous inhibitor of L-arginine (Arg)-derived nitric oxide (NO). Low circulating concentrations of homoarginine (hArg) emerged as a cardiovascular risk factor. In adults, hArg seems to antagonize ADMA. In the present work, we tested the hypothesis that children with short stature without or with GHD have altered Arg/NO pathway as compared to children with normal growth. We studied 66 short stature children (38 boys, 28 girls) aged 3.5-17.3 years, who underwent the routine L-Arginine Test to diagnose presence of GHD. GHD was confirmed in 47 children (GHD group; 30 boys, 17 girls) and was absent in the remaining 19 children (non-GHD group; 8 boys, 11 girls). In addition, we investigated 24 healthy age- and gender-matched children (10 boys, 14 girls) with normal growth. In EDTA plasma samples of all children, we determined by mass spectrometry-based methods the concentrations of Arg, hArg and ADMA, and calculated the Arg/ADMA and hArg/ADMA molar ratios. With respect to these biochemical parameters, we did not find statistically significant differences between the GHD and non-GHD groups. Comparing short with normal stature children, we found small differences regarding plasma hArg concentrations [mean ± SD; median (25th-75th percentile)]: 2.06 ± 0.52 µM; 2.12 (1.74-2.36) µM vs. 1.7 ± 0.5 µM; 1.6 (1.4-1.8) µM, P < 0.001. Compared to normal stature children, short stature children had considerably higher plasma concentrations of ADMA [0.77 ± 0.15 µM; 0.77 (0.66-0.85) µM vs. 0.57 ± 0.09 µM; 0.58 (0.50-0.63) µM, P < 0.001], but not of Arg [83.3 ± 19.2 µM; 82.2 (71.9-90.3) µM vs. 86.5 ± 17.8 µM; 84.8 (77.2-94.8) µM, P = 0.336], or the hArg/ADMA ratio [2.74 ± 0.76; 2.7 (2.2-3.1) vs. 3.1 ± 1.2; 2.85 (2.42-3.66), P = 0.161. hArg in the GHD group (r = 0.41, P = 0.004) and the hArg/ADMA ratio in both groups (r = 0.44, P = 0.002 in GHD; r = 0.55, P = 0.01 in non-GHD)], but not ADMA were positively correlated with insulin-like growth factor-1 (IGF-1). hArg and hArg/ADMA differed between girls and boys in the GHD and non-GHD groups but in the normal growth group. The hArg/ADMA ratio increased with age in all groups. Our study suggests that hArg and ADMA are involved in growth in the childhood, presumably in an antagonistic manner, with ADMA slowing and hArg accelerating growth.

Background In type 1 diabetes (T1D), the use of continuous subcutaneous insulin infusion (CSII) has increased steadily in the last years. Compared with conventional insulin injection regimes, major advantages might be a nearly physiological insulin secretion, lower rates of hypoglycemia, higher flexibility in daily life, and increased quality of life. Data on CSII in cystic fibrosis-related diabetes (CFRD) are scarce. Objective To analyze current use of insulin pumps in CFRD and compare demographics of pump-treated patients between CFRD and T1D. Methods Data from the prospective German/Austrian diabetes patient registry on insulin-treated patients with either CFRD (n = 515) or T1D (n = 43 165) aged >10 yr at manifestation of diabetes were analyzed. Results A total of 4.1% (n = 21) of CFRD and 17.7% (n = 7647) of T1D patients received insulin pump treatment within the recent year of care (p < 0.001). Pump-treated patients with CFRD had a significantly shorter duration of diabetes [median (Q1; Q3): 5.8 (2.9; 9.5) vs. 7.8 (4.3; 20.4) yr, p = 0.026] and tended to be younger [22.0 (18.2; 30.1) vs. 24.9 (17.3; 45.9) yr] than pump-treated T1D patients. Age at initiation of CSII seemed to be lower in CFRD [19.2 (16.5; 29.2) vs. 23.3 (14.8; 43.5) yr]. Insulin pump therapy was used slightly more often in male CFRD patients than females (4.7 vs. 3.6%), whereas in T1D the opposite was observed (14.9 vs. 21.2%, p < 0.001). Discontinuation rate of CSII was higher in CFRD than T1D (30.0 vs. 12.7%, p = 0.005). Conclusions Despite potential advantages, insulin pump therapy was rarely used among adolescent and young adult CFRD patients.

OBJECTIVE The prevalence of cystic fibrosis–related diabetes (CFRD) has increased with improved life expectancy of patients. Clinical and care characteristics were compared with type 1 diabetes mellitus (T1DM) in a multicenter analysis of pediatric data. RESEARCH DESIGN AND METHODS Auxological and treatment data from 47,227 patients aged younger than 21 years with CFRD or T1DM in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by multivariable mixed regression modeling. RESULTS Diabetes onset (mean [interquartile range]) occurred later in individuals with CFRD (14.5 [11.8–16.3] years) than in individuals with T1DM (8.5 [4.9–11.8] years), with female preponderance in CFRD (59.1% vs. 47.5%; P < 0.01). CFRD patients had lower BMI standard deviation scores (−0.85 [−1.59 to −0.12] vs. +0.52 [−0.10 to +1.16]; P < 0.01) and lower HbA1c (6.87% vs. 7.97%; P < 0.01). Self-monitoring of blood glucose was more frequent in patients with T1DM (4.5 vs. 3.5; P < 0.01); 72% of CFRD patients received insulin. In insulin-treated patients, insulin dosage adjusted for age, sex, and diabetes duration differed significantly (T1DM: 0.79 IE per kilogram of body weight; CFRD: 0.83 IE per kilogram of body weight). Use of short-acting and long-acting insulin analogs was significantly more frequent in T1DM (47% vs. 39% and 37% vs. 28%; both P < 0.05). Metabolic control in CFRD patients without insulin was better compared with CFRD on insulin (HbA1c: 6.00 vs. 7.12; P < 0.01), but duration of disease was significantly shorter (0.8 years [0.1–2.4] compared with 2.4 years [0.6–4.6]). There was no significant difference for BMI standard deviations scores between CFRD patients with or without insulin treatment. CONCLUSIONS Pediatric patients with CFRD show clear auxological and metabolic differences from those with T1DM, with different treatment choices.

High circulating levels of asymmetric dimethylarginine (ADMA) and low circulating levels of homoarginine (hArg) are known cardiovascular risk factors in adults. While in adults with type 1 diabetes mellitus (T1DM) circulating ADMA is significantly elevated, in children and adolescents the reported ADMA data are contradictory. In 102 children with T1DM and 95 healthy controls (HC) serving as controls, we investigated the l-arginine (Arg)/nitric oxide (NO) pathway. Children with T1DM were divided into two groups, i.e., in children with newly diagnosed diabetes mellitus [T1DM-ND; n = 10; age, 8.8 (4.4–11.2) years; HbA1c, 13 (8.9–13.9) %] and in those with long-term treatment [T1DM-T; n = 92; age, 12.5 (10.5–15.4) years; HbA1c, 8.0 (7.2–8.6) %]. The age of the HC was 11.3 (8–13.3) years. Amino acids and NO metabolites of the Arg/NO pathway, creatinine and the oxidative stress biomarker malondialdehyde (MDA) were measured by GC–MS or GC–MS/MS. Plasma hArg, ADMA and the hArg/ADMA molar ratio did not differ between the T1DM and HC groups. There was a significant difference between T1DM-T and HC with regard to plasma nitrite [0.53 (0.48–0.61) vs 2.05 (0.86–2.36) µM, P

Ein Erratum zu diesem Beitrag ist unter http://dx.doi.org/10.1007/s00112-014-3236-0 zu finden.

Background In Germany/Austria, data on medical care for cystic fibrosis-related diabetes (CFRD) is limited. Methods Anonymized data from 659 CFRD patients were analyzed and compared to the latest ADA/CFF guidelines. Results Specialized diabetes clinics were attended less frequently than recommended (3.1 vs. 4.0 times yearly). 7.9% of patients had a complete profile of examinations: diabetes education (44.9%), HbA 1c (88.8%), blood pressure (79.5%), BMI (86.5%), lipid status (37.5%), retinopathy (29.9%), microalbuminuria (33.2%), and self-monitoring of blood glucose (71.6%). HbA 1c and blood pressure were measured less frequently than recommended (2.3 and 2.0 vs. 4.0 times yearly). Overall, guidelines were followed more frequently in children than adults. Contrary to recommendations, not all patients were treated with insulin (77.2 vs. 100.0%). Insulin therapy was initiated earlier in children than adults, but there was still a substantial delay (0.9 vs. 2.7years after diagnosis, p Conclusion In CFRD patients studied, adherence to care guidelines was suboptimal.

Korrektur zu 10.1007/s00112-013-3074-5

Familial Mediterranean fever (FMF) is one the most common autoinflammatory disease (AID). Pathogenomic relevant mutations in the MEFV gene show autosomal recessive inheritance, but co-dominant mutations have been described.

The interaction of three positive inotropic compounds, which are modulators of sodium channels, with the cardiac glycoside ouabain was investigated in isolated guinea pig atria. In the presence of DPI 201-106 (3 x 10(-7) M), of its new acetidine derivative BDF 9148 (10(-7) M), or of veratridine (10(-6) M), the threshold ouabain concentration to induce toxicity was lowered by a factor of 2. This effect can be explained by the observation that specific equilibrium [3H]ouabain binding in intact atria was elevated by these compounds in the appropriate concentrations. The binding results were analyzed by means of a previously established model of "positive cooperative ouabain binding to intact myocardium," which describes the relationship between cellular sodium homeostasis and ouabain binding. The extent to which the compounds increased ouabain binding was in good quantitative agreement with the observed shift in the threshold concentration of ouabain toxicity. The increase of specific [3H]ouabain binding is likely initiated by a gain in cytosolic sodium. It takes place at the cellular level only, since a direct enhancement of [3H]ouabain binding to isolated cardiac membranes was not found. In conclusion, at least under some conditions, new inotropic drugs acting as sodium channel modulators can increase the risk of digitalis toxicity.

Systemic juvenile idiopathic arthritis (SJIA) is regarded as an autoinflammatory disease (AID) of unknown etiology related to abnormalities of the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines as interleukin (IL)-6 and IL-1.

Objectives In recent years, CF-related diabetes (CFRD) became more prevalent and is associated with a negative effect on CF outcome. To study demographics and clinical characteristics of CFRD patients documented in the standardized, multicenter German/Austrian DPV registry. Methods Until September 2014, data on 777 CFRD patients were included in the registry. Since 2013, the participating centers document lung function and type of CFTR mutation (n = 105) additionally to diabetes-related parameters. Descriptive statistics were carried out using SAS 9.4. χ 2 -test was applied for group comparisons. Results Patients aged on average 19.3 [IQR: 16.5–26.1] years and median age at CFRD diagnosis was 16.0 [13.4–20.6] years. Females were predominantly affected (58 vs. 42%, p 2 ) was present in 49.2% of patients. Glycemic control assessed by HbA1c was 6.5 [5.7–7.8]%. 75.4% of patients were treated with insulin or in combination with other glucose-lowering agents. Oral antidiabetic drugs only were used in 6.7% of patients and 17.9% received no glucose-lowering pharmacological therapy. The most common CF mutation ‘F508del homozygote' was present in 76.2% of patients. Compared to the latest national CF benchmarking report from 2012, this mutation was more common in CFRD patients (p Conclusion The study presents current data on CFRD from daily routine care. Diabetes onset is mostly around transition from pediatric care to internal medicine. Therefore, a successful and planned transition is important to provide optimal care. The previously described association between CFRD and ‘F508del homozygote' is confirmed by our data.