Clinical presentation and long-term outcome of patients with KCNJ11/ABCC8 variants: Neonatal diabetes or MODY in the DPV registry from Germany and Austria.

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.

Metabolic control during the SARS-CoV-2 lockdown in a large German cohort of pediatric patients with type 1 diabetes: Results from the DPV initiative.

OBJECTIVE: To assess if metabolic control worsened during the SARS-CoV2 lockdown in spring 2020 in youth with type 1 diabetes (T1D) in Germany. METHODS: Data from 19,729 pediatric T1D patients from the diabetes prospective follow-up (DPV) registry were available. Data sets from four time-periods between January 1 and June 30, 2020, were compared with data from the whole year 2019 in the same patient; differences were adjusted for seasonality, increasing age, and longer diabetes duration. HbA1c values from laboratory measurements and estimates derived from continuous glucose monitoring (CGM) were aggregated into a combined glucose indicator (CGI), expressed in analogy to HbA1c. RESULTS: Based on regression models adjusted for differences of sex, age, diabetes duration, and migratory background between the four time-periods, CGI values in 2020 were slightly higher than in 2019, for example, by 0.044% (0.042-0.046) (median [95% CI]) in the second lockdown month, time-period 3. Insulin dose and BMI-SDS were also marginally higher. In 2020, there were fewer hospitalizations (e.g., incidence risk ratio in time-period 3 compared with 2019: 0.52 [95% CI: 0.46-0.58]). In a subgroup of patients reporting CGM data in both years, metrics in 2020 improved: time in target increased, and mean sensor glucose fell, for example, by 2.8% (2.7-2.9), and by 4.4 mg/dl (4.3-4.6) in time-period 3. CONCLUSION: Before, during, and after the lockdown in spring 2020, metabolic control in youth with T1D in Germany did not differ significantly from the preceding year. Further effects of the ongoing pandemic on pediatric T1D patients need to be evaluated.

Undertreatment of cardiovascular risk factors in the type 1 diabetes exchange clinic network (United States) and the prospective diabetes follow-up (Germany/Austria) registries.

AIM: To examine the control of cardiovascular risk factors in type 1 diabetes (T1D) registries from the United States and Germany/Austria. MATERIALS AND METHODS: Data on individuals aged ≥12 years with T1D for ≥1 year, from the T1D Exchange Clinic Network (T1DX, United States) and the Prospective Diabetes Follow-up Registry (DPV, Germany/Austria) from 1 January 2016 to 31 March 2018 were analysed. Linear and logistic regression models adjusted for age groups, sex, duration of diabetes and minority status were used to compare clinical characteristics and achievement of diabetes management targets between registries. RESULTS: The cohort consisted of 47 936 patients (T1DX, n = 19 442; DPV, n = 28 494). Achievement of HbA1c goals (<7.0%, ages 18-65 years; all others, <7.5%) was better in the DPV for those aged <65 years (all P < .001). However, more older adults (aged ≥65 years) in the T1DX achieved an HbA1c goal of <7.5% compared with DPV (70% vs. 50%, P < .001). The frequency of patients with overweight (53% vs. 51%, P < .001) and obesity (19% vs. 9%, P < .001) was higher in T1DX. The frequency of meeting blood pressure goals (84% vs. 66%, P < .001) and lipid goals (73% vs. 62%, P < .001) was higher in T1DX; this was observed across all age groups (all P < .001). Few young adults aged <26 years received antihypertensive and lipid-lowering medications, respectively, despite indications in both registries (T1DX: 5% and 3%, DPV: 3% and 1%). CONCLUSION: A minority of patients with T1D achieve glycaemic targets and the majority are inadequately treated for hypertension and dyslipidaemia. This highlights the need for improved diabetes and cardiovascular risk management strategies in T1D.

Oral contraception in adolescents with type 1 diabetes and its association with cardiovascular risk factors. A multicenter DPV study on 24 011 patients from Germany, Austria or Luxembourg.

OBJECTIVE: To investigate differences in cardiovascular risk factors and metabolic control in girls with type 1 diabetes with or without use of oral contraceptives (OC) from the multicenter "diabetes prospective follow-up" (DPV) registry. METHODS: Twenty-four thousand eleven adolescent girls (13 to < 18 years of age) from Germany, Austria or Luxembourg with type 1 diabetes from the DPV registry were included in this cross-sectional study. Multivariable regression models were applied to compare clinical characteristics (hemoglobin A1c [HbA1C ], blood pressure, serum lipids, body mass index) and lifestyle factors (smoking, physical inactivity, alcohol consumption) between girls with or without OC use. Confounders: age, diabetes duration and migration background. STATISTICAL ANALYSIS: SAS 9.4. RESULTS: In girls with type 1 diabetes and OC use, clinical characteristics and lifestyle factors were less favorable compared to non-users. Differences were most pronounced for the prevalence of dyslipidemia (OC-users: 40.0% vs non-users: 29.4; P < .0001) and the number of smokers (OC-users: 25.9% vs non-users: 12.5%; P < .0001). OC use, sociodemographic characteristics and lifestyle factors explained between 1 and 7% of the population variance in serum lipids and blood pressure. The use of OC explained a small additional proportion in all variables considered (<1%). CONCLUSIONS: OC use in adolescent girls with type 1 diabetes was associated with a poorer cardiovascular risk profile. Biological risk factors were partly explained by a clustering of sociodemographic and lifestyle factors with a small additional contribution of OC use. Prescription of OC should therefore be combined with a screening for cardiovascular risk factors and targeted education.

Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose-adjusted HbA1c in 3657 children and adolescents from Germany and Austria.

OBJECTIVE: Insulin dose-adjusted hemoglobin A1c (HbA1C, IDAA1c) correlates well with stimulated C-peptide levels, but has not yet been evaluated in a large cohort of patients with Type 1 diabetes (T1D). METHODS: We investigated prevalence of partial remission (PREM) defined by IDAA1c ≤9 in 3657 in children with new-onset T1D who were continuously followed over 6 years. We evaluated the predictors of PREM using the multicenter database from the DPV (Diabetes Patienten Verlaufsdokumentation) registry. RESULTS: PREM occurred in 71% of patients. Median duration was 9 (0-21) months. Compared to children <5 years at T1D onset, those aged 5-10 and ≥10 years had twice the chance of developing PREM (OR: 2.08, CI: 1.67-2.60; P < .001 and OR: 2.16, CI: 1.70-2.75; P < .001). Boys were more likely to develop PREM than girls (OR 1.41, CI: 1.18-1.69; P = .0002). Further predictors for PREM were: ketoacidosis, autoantibodies, and HbA1c at T1D onset. These results were confirmed by quantile regression analysis with duration of PREM as dependent variable. CONCLUSION: This research on a large cohort provides insight into epidemiologic characteristics of PREM in T1D defined by IDAA1c. As IDAA1c does not discriminate between insulin sensitivity and secretion, available data cannot resolve whether the sex-difference in PREM reflects innate higher insulin resistance in girls, or better beta-cell recovery in boys. Further research is needed to clarify the usefulness and performance of IDAA1c in clinical practice.

Non-High-Density Lipoprotein Cholesterol in Children with Diabetes: Proposed Treatment Recommendations Based on Glycemic Control, Body Mass Index, Age, Sex, and Generally Accepted Cut Points.

Percentile-based non-high-density lipoprotein cholesterol levels were analyzed by glycemic control, weight, age, and sex of children with type 1 diabetes (n = 26,358). Ten percent of all children and 25% of overweight adolescent girls require both immediate lipid-lowering medication and lifestyle changes to achieve non-high-density lipoprotein cholesterol levels <120 mg/dL and cardiovascular risk reduction.

Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States.

OBJECTIVE: To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D). STUDY DESIGN: International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed. RESULTS: Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant. CONCLUSIONS: Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

Tracking of metabolic control from childhood to young adulthood in type 1 diabetes.

OBJECTIVE: This prospective longitudinal survey was designed to follow patients with diabetes from disease onset in childhood over an extended period of time including puberty until young adulthood with respect to metabolic control. STUDY DESIGN: An electronic diabetes patient documentation system used in diabetes centers in Austria and Germany was utilized for standardized data collection. Complete documentation of metabolic control for prepuberty (≤ 13 years), puberty (14-19 years), and adulthood (≥ 20 years) was available in 1146 patients. RESULTS: Median age at diabetes manifestation was 7.2 (IQR 4.7-9.4) years; 49% were male. In the prepubertal stage, median glycated hemoglobin A1c (HbA1c) was 7.5 (IQR 6.8-8.3), during puberty 8.0 (IQR 7.3-8.9), and after puberty 7.8 (IQR 7.1-9.0). A significant intra-individual correlation was found for prepuberty to puberty HbA1c levels (R = 0.55, P < .001), puberty to adulthood (R = 0.59, P < .001), as well as prepuberty to adulthood (R = 0.30, P < .001). When patients were divided into tertiles of prepubertal HbA1c, HbA1c increased in all 3 groups over time, however, significant group differences tracked into adulthood (P < .001 at all stages). A regression model identified pre-pubertal HbA1c as a significant and relevant predictor of metabolic control in young adulthood adjusted for confounders (P < .001). CONCLUSIONS: This survey provides evidence for long-term tracking of metabolic control from childhood until adulthood, suggesting an early focus on metabolic control.

Algorithm-based cholesterol monitoring in children with type 1 diabetes.

OBJECTIVE: To facilitate child-specific and diabetes-related cholesterol control, we developed a monitoring algorithm derived from population-based reference values. STUDY DESIGN: Low-density lipoprotein (LDL)-, non-high-density lipoprotein (HDL)-, and HDL cholesterol percentile values were calculated for children with type 1 diabetes (T1D) and their peers without T1D within algorithm-based categories of sex, age: 1-10 vs >10-<18 years, body mass index: <90th vs ≥90th percentile, and hemoglobin A1c <6%, 6%-<7.5%, 7.5%-9%, >9%. Analyses included 26 147 patients sampled from a German/Austrian population-based registry for T1D (Diabetes Documentation and Quality Management System) and 14 057 peers without diabetes participating in the national Health Interview and Examination Survey for Children and Adolescents in Germany. RESULTS: Reference percentile values for cholesterol were derived as a diagnostic algorithm aimed at supporting long-term cholesterol control. Taking account of a patient's sex, age-group, weight-, and hemoglobin A1c-category, the flowcharts of the algorithm developed separately for LDL-, non-HDL-, and HDL cholesterol allow comparing his/her cholesterol levels with population-based reference percentile values of peers without T1D. CONCLUSIONS: The population-based algorithmic approach applied to LDL-, non-HDL-, and HDL cholesterol allows referencing children with T1D with regard to their peers without T1D and, if necessary, suggests corrections of glycemic control to optimize long-term cholesterol levels.

Pulse pressure in children and adolescents with type 1 diabetes mellitus in Germany and Austria.

BACKGROUND: Impaired blood pressure regulation contributes to the development of diabetic complications. The influence of systolic (SBP) vs.diastolic blood pressure (DBP) is still controversial. Peripheral pulse pressure(PP), the difference between SBP and DBP, is an indicator for arterial stiffness. Only little data are available for PP in children. Therefore, we studied PP regulation in type 1 diabetic children and adolescents.Methods: Blood pressure values of 46 737 patients with T1DM younger than 20 years are documented in the DPV database and were compared with the control populations of the '4th report on high blood pressure (4th report)' and the German KIGGS study. RESULTS: PP is increased in 63% (4th report) or 67% (KIGGS) of the patients,respectively. The rate of increased PP remains stable between 59 and 68%,irrespective of sex, age, and the control population. Absolute PP is elevated independently of the control population (PP T1DM 49.13±11.1 vs. 4th report 45.38 ± 3 vs. KIGGS 44.58 ± 4.6 mmHg; all p<0.0001, Wilcoxon test)and increases with age in both sexes. Age, male sex, diabetes duration, insulin dose, and body mass index (BMI) are independent factors contributing to elevated absolute PP levels and to the prevalence of wide PP. HbA1c is negligible negatively related to increased PP levels (multiple linear regression). CONCLUSIONS: In T1DM increased PP is a marker for accelerated arterial stiffness and aging and should be considered as an additional risk factor in the treatment of diabetic children. Elevated PP in children with T1DM may contribute to the high risk for early development of atherosclerosis.

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.

Urinary Protein-Biomarkers Reliably Indicate Very Early Kidney Damage in Children With Alport Syndrome Independently of Albuminuria and Inflammation.

Introduction: Alport syndrome (AS) is a hereditary type IV collagen disease. It starts shortly after birth, without clinical symptoms, and progresses to end-stage kidney disease early in life. The earlier therapy starts, the more effectively end-stage kidney disease can be delayed. Clearly then, to ensure preemptive therapy, early diagnosis is an essential prerequisite. Methods: To provide early diagnosis, we searched for protein biomarkers (BMs) by mass spectrometry in dogs with AS stage 0. At this very early stage, we identified 74 candidate BMs. Of these, using commercial enzyme-linked immunosorbent assays (ELISAs), we evaluated 27 in dogs and 28 in children, 50 with AS and 104 healthy controls. Results: Most BMs from blood appeared as fractions of multiple variants of the same protein, as shown by their chromatographic distribution before mass spectrometry. Blood samples showed only minor differences because ELISAs rarely detect disease-specific variants. However, in urine , several proteins, individually or in combination, were promising indicators of very early and preclinical kidney injury. The BMs with the highest sensitivity and specificity were collagen type XIII, hyaluronan binding protein 2 (HABP2), and complement C4 binding protein (C4BP). Conclusion: We generated very strong candidate BMs by our approach of first examining preclinical AS in dogs and then validating these BMs in children at early stages of disease. These BMs might serve for screening purposes for AS before the onset of kidney damage and therefore allow preemptive therapy.

Association of epilepsy and type 1 diabetes mellitus in children and adolescents: is there an increased risk for diabetic ketoacidosis?

OBJECTIVE: To estimate the prevalence of epilepsy and possible risk factors in children and adolescents with diabetes mellitus. STUDY DESIGN: We conducted an observational cohort study based on the Diabetes Patienten Verlaufsdokumentation database including data from 45 851 patients (52% male) with type 1 diabetes mellitus, age 13.9 ± 4.3 years (mean ± SD) and duration of diabetes mellitus 5.4 ± 4.2 years. The database was searched for the concomitant diagnosis of epilepsy or epileptic convulsions and for antiepileptic medication. RESULTS: A total of 705 patients with epilepsy were identified, giving a prevalence of 15.5 of 1000. A total of 375 patients were treated with antiepileptic medication, and 330 patients were without anticonvulsive therapy. Patients with epilepsy were younger at onset of diabetes mellitus and shorter than patients without epilepsy, and their weight and body mass index were comparable. No difference could be demonstrated for metabolic control, type of insulin treatment, insulin dose, and prevalence of B-cell specific autoantibodies. The frequency of severe hypoglycemia was lower in patients treated with antiepileptic medication. The risk for diabetic ketoacidosis was almost double in patients with epilepsy compared with patients with type 1 diabetes mellitus alone (P < .01). CONCLUSION: Children and adolescents with diabetes mellitus show an increased prevalence of epileptic seizures. For unknown reasons, there is an association between epilepsy and diabetic ketoacidosis in children with type 1 diabetes mellitus.

Growth in children and adolescents with type 1 diabetes.

OBJECTIVE: To investigate the effect of type 1 diabetes on growth and adult height. STUDY DESIGN: Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients. RESULTS: At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of -0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (-0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (-0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015). CONCLUSION: Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.

Diabetic Ketoacidosis at Manifestation of Type 1 Diabetes in Childhood and Adolescence­Incidence and Risk Factors.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening metabolic disorder that can occur with manifestation of type 1 diabetes mellitus (T1D). The aim of this study was to analyze the incidence of DKA at the time of the diagnosis of T1D in childhood and adolescence, the risk factors, and regional approaches to reduce the incidence of ketoacidosis. METHODS: We investigated the proportion of patients under 18 years of age with DKA (defined as pH <7.3, severe DKA pH <7.1) at the manifestation of T1D in Germany in the period 2000-2019, based on data from the German-Austrian registry of diabetes (Diabetes-Patienten-Verlaufsdokumentation, DPV). The influence of the following factors was evaluated: year of manifestation, age, sex, family history of migration (MiH), and distance from the hospital. Moreover, data from the region with and the region without a pilot screening project from 2015 onwards were compared. RESULTS: Of the 41 189 patients with manifestation of T1D, 19.8% presented with DKA (n = 8154, slight increase [p <0.001] over the study period) and 6.1% (n = 2513) had severe DKA. Children under 6 years of age had DKA more often than adolescents (12-17 years) (21.7% versus 18.6%, OR 1.22 {95% CI: [1.14; 1.30]}). Girls had a higher rate of DKA than boys (20.5% versus 19.2%, OR 1.10 [1.03; 1.14]), and patients with MiH were more likely to have DKA than those without MiH (21.4% versus 18.2%, OR 1.40 [1.32; 1.48]). In the region with a pilot screening project, the DKA rate stayed the same, at 20.6%, while in the control region the rate was 22.7% with a decreasing tendency. CONCLUSION: The frequency of DKA at the time of diagnosis of T1D did not decrease between 2000 and 2019 and increased towards the end of the observation period. Children with MiH, children under 6, and girls were at a higher risk of DKA.

Sex differences over time for glycemic control, pump use and insulin dose in patients aged 10-40 years with type 1 diabetes: a diabetes registry study.

INTRODUCTION: To evaluate sex differences in people with type 1 diabetes concerning changes in glycemic control and trends in insulin pump use and insulin dose over two decades in adolescents and one-and-a-half decades in adults. RESEARCH DESIGN AND METHODS: People aged 10-20 years (data years 1999-2018) and 21-40 years (data years 2004-2018) with type 1 diabetes were identified in the Diabetes Prospective Follow-up Registry (DPV). All available patients' data sets of the respective period were used for linear regression analyses to investigate trends in HbA1c, pump use, insulin doses and body mass index SD scores (BMI-SDS) in females and males. In addition, stratification by migrant background was made for the adolescent group. RESULTS: In the youth group (n=68 662), both boys and girls showed an HbA1c decrease over the period examined. After stratification for migrant background, an HbA1c convergence between boys and girls was seen in those without migrant background as of 2016. Usage of insulin pumps increased continuously from 3% (boys and girls) to 47% (boys) and 54% (girls), respectively. The daily insulin dose in units per kilogram body weight and day increased continuously from 1999 to 2018. An insulin dose leveling between boys and girls occurred. BMI-SDS consistently increased in girls whereas only slight variations were observed in boys.The adult group (n=15 380) showed constant HbA1c sex differences from 2004 to 2018 with lower HbA1c level in females. The use of insulin pump therapy rose from 18% to 35% (males) and 30% to 50% (females). CONCLUSIONS: The gap in metabolic control between boys and girls with type 1 diabetes seems to close, but predominantly in adolescents without a migrant background. Improved HbA1c was associated with increased insulin pump use, especially in girls.In adult patients, sex differences in metabolic control and insulin pump use persist: women show constantly lower HbA1c values and higher insulin pump use.

Frequency of Autoantibody-Negative Type 1 Diabetes in Children, Adolescents, and Young Adults During the First Wave of the COVID-19 Pandemic in Germany.

OBJECTIVE: The aim of this study was to investigate the frequency of newly diagnosed type 1 diabetes without evidence of autoimmunity and the respective frequencies of ketoacidosis in children, adolescents, and young adults during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with the previous decade. RESEARCH DESIGN AND METHODS: Based on data from the German Diabetes Prospective Follow-up Registry (DPV), we compared data from 715 children, adolescents, and young adults, newly diagnosed with type 1 diabetes during the COVID-19 pandemic in Germany between 1 March and 30 June 2020, with data from 5,428 children, adolescents, and young adults of the same periods from 2011 to 2019. Adjusted differences and relative risks (RRs) of negative ß-cell autoantibody test results and diabetic ketoacidosis were estimated using multivariable log-binomial regression analysis. An upper noninferiority test (margin 1%) was applied to evaluate whether the autoantibody-negativity rate in 2020 was not higher than that in 2011 to 2019. RESULTS: The estimated frequencies of autoantibody negativity in 2020 and 2011-2019 were 6.6% (95% CI 5.1-8.4) and 7.2% (95% CI 6.5-8.0), respectively, with an absolute difference of -0.68% (90% CI -2.07 to 0.71; P upper noninferiority = 0.023). The increase of the estimated frequency of diabetic ketoacidosis during the COVID-19 pandemic was similar between autoantibody-negative and -positive type 1 diabetes (adjusted RRs 1.28 [95% CI 0.80-2.05] and 1.57 [1.41-1.75], respectively). CONCLUSIONS: This study found no evidence that the COVID-19 pandemic leads to a significantly increased number of new cases with autoantibody-negative type 1 diabetes in children, adolescents, and young adults. In addition, autoantibody-negative type 1 diabetes showed no particular susceptibility to ketoacidosis, neither before nor during the pandemic.

Initial insulin therapy in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: The aim of the study was to define parameters that influence the initial insulin dosage in young subjects with type 1 diabetes regarding the amount of daily insulin, the ratios of basal and prandial insulin, and the insulin/carbohydrate ratios. STUDY DESIGN: We used a computer-based registry (with prospectively collected data) in Germany and Austria, a software for the management and data documentation of diabetic patients (DPV), to analyze the initial insulin therapy in 2247 children with newly diagnosed type 1 diabetes to identify factors that influence diabetes therapy within the first 10 d. RESULTS: For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals. The frequency of hypoglycemia correlated with increasing quotient of applied to calculated insulin dosage. CONCLUSION: The predictive factors of insulin requirement may exert beneficial effects on the assessment and adjustment of insulin therapy in young diabetic subjects at disease onset. On the basis of a multiple, linear regression, we suggest a formula to calculate the initial insulin therapy.

Bone maturation in 1788 children and adolescents with diabetes mellitus type 1.

Diabetes mellitus type 1 might interfere with pubertal development. Particularly, long-term metabolic control and intensity of insulin treatment have been reported to contribute to a delay in pubertal onset. Data on somatic development in diabetic children are conflicting; therefore we studied bone age in 1788 children from Germany and Austria with type 1 diabetes. Bone age was retarded by -0.27 +/- 1.1 years in the whole group, but particularly in the adolescents at the end of puberty (>16 years; -0.76 +/- 1.29y). Bone age delay was more pronounced in boys, and in children with long-term median HbAlc levels of 7.5 - 9.0%. No associations were found with current HbAlc levels or the intensity of insulin treatment. Bone age determinations in diabetic children should only be performed when clinical signs of impaired somatic development are present. In addition, the potential influence of diabetes on bone development needs to be considered in the interpretation of carpograms.