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Objective: To describe clinical presentation/longterm outcomes of patients with ABCC8/KCNJ11 variants in a large cohort of patients with diabetes. Research Design and Methods: We analyzed patients in the Diabetes Prospective Follow‐up (DPV) registry with diabetes and pathogenic variants in the ABCC8/KCNJ11 genes. For patients with available data at three specific time‐points—classification as K+‐channel variant, 2‐year follow‐up and most recent visit—the longitudinal course was evaluated in addition to the cross‐sectional examination. Results: We identified 93 cases with ABCC8 (n = 54)/KCNJ11 (n = 39) variants, 63 of them with neonatal diabetes. For 22 patients, follow‐up data were available. Of these, 19 were treated with insulin at diagnosis, and the majority of patients was switched to sulfonylurea thereafter. However, insulin was still administered in six patients at the most recent visit. Patients were in good metabolic control with a median (IQR) A1c level of 6.0% (5.5–6.7), that is, 42.1 (36.6–49.7) mmol/mol after 2 years and 6.7% (6.0–8.0), that is, 49.7 (42.1–63.9) mmol/mol at the most recent visit. Five patients were temporarily without medication for a median (IQR) time of 4.0 (3.5–4.4) years, while two other patients continue to be off medication at the last follow‐up. Conclusions: ABCC8/KCNJ11 variants should be suspected in children diagnosed with diabetes below the age of 6 months, as a high percentage can be switched from insulin to oral antidiabetic drugs. Thirty patients with diabetes due to pathogenic variants of ABCC8 or KCNJ11 were diagnosed beyond the neonatal period. Patients maintain good metabolic control even after a diabetes duration of up to 11 years. [ABSTRACT FROM AUTHOR]

Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio [OR] 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of overweight and obesity in childhood and adolescence are rapidly increasing and influenced by genetic, familial, environmental, socioeconomic and cultural factors. The aim of the study was to compare risk factors for childhood obesity in Ukraine (UA) and Germany (DE) using comparable investigative tools. Methods: Two groups of children, aged 8 to 18 years, from DE (93 children) and UA (95 children) were divided into overweight and obese groups. Anthropometric data and detailed medical history were collected. Results: Risk factors in pregnancy (prematurity, weight gain >20 kg, early contractions) were equally frequent in both groups. Positive correlations of body mass index (BMI)-standard deviation score (SDS) between children and mothers were noted. The proportion of family members with diabetes mellitus was lower in the UA group. Obesity was more frequent at one year of age in DE children. The DE group also became overweight at an earlier age and remained overweight over a longer period of time compared to UA. The mean BMI-SDS of obese children was lower in the UA group. In both groups waist circumference to height ratio was >0.5, indicating presence of a cardiometabolic risk factor. About half of the patients in both groups had blood pressure values exceeding the 95th percentile. Conclusion: Similar risk factors for obesity were observed among two groups of children in UA and DE. Differences were observed regarding the prevalence of specific risk factors for childhood obesity. Population-specific distribution of risk factors needs to be considered in order to optimize prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: With increasing migration to Europe, diabetes diagnosis and treatment of refugees became challenging. To describe the current experience with pediatric refugees in Germany and Austria. Design and Methods: 43,137 patients (<21 years) with type 1 diabetes from the diabetes patient follow -up registry (DPV) were studied and divided by refugee status into patients born in Middle East (n = 365) or Africa (n = 175) and native patients (child and parents born in Germany/Austria; G/A: n = 42,597). Groups were compared using multivariable regression adjusted for age, sex and diabetes duration (SAS 9.4). In refugees the first year after arrival was studied, and for native children the most recent year of care. Results: After adjustment, HbA1c was highest in refugees (1. ME and 2. AFR vs 3. G/A: 72.3 ± 1.0 and 75.0 ± 1.4 vs 66.0 ± 0.1 mmol/mol, 1 vs 3: P < 0.001 and 2 vs 3: P < 0.001) and microalbuminuria (9.9 and 13.6 vs 6.5%, 1 vs 3: P = 0.039 and 2 vs 3: P = 0.002) was more prevalent. African children experienced severe hypoglycemia (17.8 ± 4.3 and 25.4 ± 8.7 vs 11.5 ± 0.3 per 100 patient years, 1 vs 3: P > 0.05 and 2 vs 3: P = 0.045) significantly more often, whereas hypoglycemia with coma (5.1 ± 1.1 and 4.1 ± 1.6 vs 2.6 ± 0.1 per 100 patient years, 1 vs 3: P = 0.006 and 2 vs 3: P > 0.05) and retinopathy (2.1 and n/a vs 0.2%, 1 vs 3: P < 0.001) were significantly more common in children from Middle E ast compared to natives. Insulin pumps were used in a markedly larger proportion of native patients (7.4 and 13.2 vs 43.0%, 1 vs 3: P < 0.001 and 2 vs 3: P < 0.001). Conclusions: A relevant number of pediatric refugees with type 1 diabetes are treated in German/Austrian diabetes clinics. Refugee children, parents and caregivers are faced with several problems in diabetes therapy and outcome that should be addressed more intensively by pediatric diabetes teams. [ABSTRACT FROM AUTHOR]

Objective: There is evidence that transition from pediatric to adult health care is frequently associated with deterioration of health in youths with type 1 diabetes (T1D). The aim of this study was to compare metabolic control, acute complications and microvascular complications in adolescents and young adults before and after transfer to an adult treatment center with respect to the time between first visit in the adult center and last visit in pediatric treatment. Methods: All data were collected during routine care and retrieved from the German/Austrian DPV database. We analyzed data as of March 2017. Results: We found 1283 young adults with available data of the last pediatric treatment year and the first year after transition to adult care. HbA1c increased significantly from 8.95% (74 mmol/mol) before to 9.20% (77 mmol/mol) in the first year after transition. Frequency of DKA with hospitalization (0.10‐0.191 per annum, P < .0001) and severe hypoglycemia (0.23‐0.46 per annum, P = .013) doubled during transition. Microvascular complications increased dramatically depending on the time between first visit in adult treatment and last visit in pediatric care. We could not find a significant correlation of this rise of microvascular complications to the duration of transition (short or long). Conclusion: This phase of life bears a high risk for detrimental outcome in young adults with T1D. Structured transition programs with case management are therefore needed to improve the transition process and outcomes. [ABSTRACT FROM AUTHOR]

Objective: Worsening of glycemic control in type 1 diabetes during puberty is a common observation. However, HbA1c remains stable or even improves for some youths. The aim is to identify distinct patterns of glycemic control in type 1 diabetes from childhood to young adulthood.Research Design and Methods: A total of 6,433 patients with type 1 diabetes were selected from the prospective, multicenter diabetes patient registry Diabetes-Patienten-Verlaufsdokumentation (DPV) (follow-up from age 8 to 19 years, baseline diabetes duration ≥2 years, HbA1c aggregated per year of life). We used latent class growth modeling as the trajectory approach to determine distinct subgroups following a similar trajectory for HbA1c over time.Results: Five distinct longitudinal trajectories of HbA1c were determined, comprising group 1 = 40%, group 2 = 27%, group 3 = 15%, group 4 = 13%, and group 5 = 5% of patients. Groups 1-3 indicated stable glycemic control at different HbA1c levels. At baseline, similar HbA1c was observed in group 1 and group 4, but HbA1c deteriorated in group 4 from age 8 to 19 years. Similar patterns were present in group 3 and group 5. We observed differences in self-monitoring of blood glucose, insulin therapy, daily insulin dose, physical activity, BMI SD score, body-height SD score, and migration background across all HbA1c trajectories (all P ≤ 0.001). No sex differences were present. Comparing groups with similar initial HbA1c but different patterns, groups with higher HbA1c increase were characterized by lower frequency of self-monitoring of blood glucose and physical activity and reduced height (all P < 0.01).Conclusions: Using a trajectory approach, we determined five distinct longitudinal patterns of glycemic control from childhood to early adulthood. Diabetes self-care, treatment differences, and demographics were related to different HbA1c courses. [ABSTRACT FROM AUTHOR]

Background With increasing obesity in childhood and adolescence, weight gain, and insulin resistance become also more frequent in patients with type 1 diabetes mellitus (T1DM). Especially during puberty, insulin therapy often has to be intensified and higher insulin doses are necessary. Some studies point to a beneficial effect of metformin in addition to insulin in these patients. In order to describe current practice and possible benefits, we compared pediatric T1DM patients with insulin plus metformin (n = 525) to patients with insulin therapy only (n = 57 487) in a prospective multicenter analysis. Methods Auxological and treatment data from 58 012 patients aged <21 yr with T1DM in the German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registry were analyzed by multivariable mixed regression modeling. Results Patients with additional metformin were older [median (interquartile range)]: [16.1 (14.1-17.6) vs. 15.2 (11.5-17.5) yr] with female preponderance (61.0 vs. 47.2%, p < 0.01). They had higher body mass index-standard deviation score (BMI-SDS) [+2.03 (+1.29 to +2.56) vs. +0.51 (−0.12 to +1.15); p < 0.01] and glycated hemoglobin (HbA1c) (9.0 vs. 8.6%, p < 0.01). Hypertension (43.7 vs. 24.8%) and dyslipidemia (58.4 vs. 40.6%) were significantly more prevalent. Adjusted insulin dose was significantly higher (0.98 vs. 0.93 IU/kg bodyweight). In a subgroup of 285 patients followed-up longitudinally (average treatment period 1.42 yr), addition of metformin resulted in a slight reduction of BMI-SDS [−0.01 (−2.01 to +1.40)], but did not improve HbA1c or insulin requirement. Conclusion Additional metformin therapy in T1DM is primarily used in obese females. Additional therapy with metformin was associated with minor benefits. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of hospitalization especially in young children with respiratory tract infections (RTI). Patterns of circulating RSV genotypes can provide a better understanding of the molecular epidemiology of RSV infection. We retrospectively analyzed the genetic diversity of RSV infection in hospitalized children with acute RTI admitted to University Hospital Heidelberg/Germany between October 2012 and April 2013. Nasopharyngeal aspirates (NPA) were routinely obtained in 240 children younger than 2 years of age who presented with clinical symptoms of upper or lower RTI. We analyzed NPAs via PCR and sequence analysis of the second variable region of the RSV G gene coding for the attachment glycoprotein. We obtained medical records reviewing routine clinical data. RSV was detected in 134/240 children. In RSV-positive patients the most common diagnosis was bronchitis/bronchiolitis (75.4%). The mean duration of hospitalization was longer in RSV-positive compared to RSV-negative patients (3.5 vs. 5.1 days; p<0.01). RSV-A was detected in 82.1%, RSV-B in 17.9% of all samples. Phylogenetic analysis of 112 isolates revealed that the majority of RSV-A strains (65%) belonged to the novel ON1 genotype containing a 72-nucleotide duplication. However, genotype ON1 was not associated with a more severe course of illness when taking basic clinical/laboratory parameters into account. Molecular characterization of RSV confirms the co-circulation of multiple genotypes of subtype RSV-A and RSV-B. The duplication in the G gene of genotype ON1 might have an effect on the rapid spread of this emerging RSV strain. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 709–712 (2010) Aims The aim of this study was to elucidate the entities and the frequency of neonatal diabetes mellitus (NDM) in a large representative database for paediatric diabetes patients in Germany and Austria. Methods Based on the continuous diabetes data acquisition system for prospective surveillance (DPV), which includes 51 587 patients with onset of diabetes before the age of 18 years from 299 centres in Germany and Austria, we searched for patients with onset of diabetes mellitus in the first 6 months of life. Results Ninety patients were identified, comprising 0.17% of all paediatric cases in the DPV registry. This represented an incidence of approximately one case in 89 000 live births in Germany. A monogenic basis for NDM was established in 30 subjects (seven UPD6, 10 KCNJ11, seven ABCC8, two FOXP3, two PDX1, one INS, one EIF2AK3). Pancreatic hypoplasia or agenesis was reported in 10 patients and seven subjects were classified as having Type 1 diabetes by their centres. Transient neonatal diabetes (TNDM) accounted for approximately 10% of all cases with NDM. No aetiology was defined in 41 subjects, which may reflect incomplete genetic testing or novel genetic aetiologies. Conclusion Based on a large database, we identified a higher rate of NDM in Germany than has been reported previously. Full molecular genetic testing should be performed in all patients diagnosed before 6 months of age. [ABSTRACT FROM AUTHOR]

Aims: To study the frequency of mutations in the Pax8 gene in a cohort of patients with congenital hypothyroidism (CH) in South West Germany. Methods: A cohort of 95 patients with CH (60 females, 35 males), identified in our newborn screening program, was analyzed for mutations in Pax8 by single-stranded conformational polymorphism (SSCP) and DNA sequencing. Results: SSCP analysis and direct sequencing of exon 3 of a female patient with a hypoplastic thyroid gland revealed two heterozygous mutations in Pax8 resulting in a transition of T to C (codon 34) and G to A (codon 35), replacing isoleucine by threonine and valine by isoleucine. Using allele-specific PCR we could demonstrate that both mutations are located on the same allele. Furthermore, a polymorphism was documented in 24 patients with thyroid hypoplasia in intron 6 at nucleotide +51 (CC, GG, CG). Comparison of the polymorphisms between hypothyroid patients and controls revealed no significant differences suggesting that this polymorphism does not play a role in the pathogenesis of hypothyroidism. No further mutations or polymorphisms were found in the cohort. Conclusions: These findings confirm the contribution of mutations in the Pax8 gene to the etiology of thyroid dysgenesis with a variable penetrance, but also demonstrate the rare overall incidence in CH. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of hopitalisation in young children with respiratory tract infections (RTI). The aim of this research project was to analyse RSV genotypes and the diversification of RSV strains among hospitalised children in Heidelberg, Germany. We prospectively analysed nasopharyngeal swabs (NPS) from children who were hospitalised with acute RTI at the University Hospital Heidelberg, Germany, during winter seasons 2014 to 2017. RSV RT-PCR and RSV sequence analysis of the G gene coding for the attachment glycoprotein were performed. Clinical data was obtained using a standardised questionnaire. RSV was detected in 405 out of 946 samples from hospitalised children. Most RSV positive children were below the age of two years (84.4%) and had a lower RTI (78.8%). The majority of RSV positive children was male, significantly younger than RSV negative children with a median age of 0.39 years and with more severe respiratory symptoms. Out of 405 positive samples, 317 RSV strains were successfully sub-grouped into RSV subtypes A (57.4%; 182/317) and B (42.6%; 135/317). Both RSV subtypes cocirculated in all analysed winter seasons. Phylogenetic analysis of 317 isolates revealed that the majority of RSV-A strains (180/182) belonged to the ON1 genotype, most RSV-B strains could be attributed to the BAIX genotype (132/135). ON1 and BAIX strains showed a sub-differentiation into different lineages and we were able to identify new (sub)genotypes. Analysis of the molecular epidemiology of RSV from different seasons revealed the cocirculation and diversification of RSV genotypes ON1 and BAIX. • RSV is an important cause for hospitalization of children in Heidelberg/Germany. • RSV subtypes A and B cocirculated in all winter seasons 2014–2017. • The majority of RSV-A strains belonged to the ON1 genotype. • Most RSV-B strains could be attributed to the BAIX genotype. • Genotypes ON1 and BAIX cocirculation and diversified across all seasons. [ABSTRACT FROM AUTHOR]