Elevated liver enzymes and comorbidities in type 2 diabetes: A multicentre analysis of 51 645 patients from the Diabetes Prospective Follow-up (DPV) database.

AIM: To assess the prevalence of elevated liver enzymes and associated diabetes-related comorbidities in type 2 diabetes (T2D). SUBJECTS AND METHODS: Between 2010 and 2019, 281 245 patients with T2D (aged 18-75 years) from 501 Diabetes Prospective Follow-up (DPV) centres were evaluated, resulting in analysis of 51 645 patients with complete data on demographics and liver enzymes. RESULTS: Elevated liver enzymes were found in 40.2% of all patients. However, only 8.6% of these patients had International Classification of Diseases-10 codes for nonalcoholic fatty liver disease and/or nonalcoholic steatohepatitis. Adjusted for age, sex, diabetes duration, body mass index and glycated haemoglobin, a higher prevalence of arterial hypertension (P < 0.0001), dyslipidaemia (P < 0.0001), peripheral artery disease (P = 0.0029), myocardial infarction (P = 0.0003), coronary artery disease (P = 0.0001), microalbuminuria (P < 0.0001) and chronic kidney disease (P < 0.0001) was seen in patients with elevated versus normal liver enzymes. The prevalence of elevated liver enzymes was lowest in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors or a combination of SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. CONCLUSION: Elevated liver enzymes are common in patients with T2D and clearly correlate with a higher prevalence of clinically relevant comorbidities. Assessing liver enzymes should be standard clinical routine in T2D due to a possible predictive role for comorbidities and complications.

Glycated hemoglobin at diagnosis of type 1 diabetes and at follow-up in children and adolescents during the COVID-19 pandemic in Germany.

BACKGROUND: This study investigated the diagnostic delay and the subsequent quality of care during the Covid-19 pandemic among children with new-onset type 1 diabetes. METHODS: We compared the HbA1c levels of 3111 children at diagnosis of type 1 diabetes and of 2825 children at a median follow-up of 4.7 months (interquartile range, 4.1-5.4) together with their daily insulin requirement during the Covid-19 pandemic with the two previous years via multivariable linear regression, using data from the German Diabetes Registry DPV. RESULTS: During the Covid-19 pandemic, HbA1c levels were higher at diagnosis of type 1 diabetes (mean estimated difference, 0.33% [95% confidence interval, 0.23-0.43], p < 0.001), but not at follow-up (mean estimated difference, 0.02% [-0.02-0.07]). Children with diabetes onset during the Covid-19 pandemic had a significantly higher daily insulin requirement after initiation of therapy (mean estimated difference, 0.08 U/kg [0.06-0.10], p < 0.001). Both the increase in HbA1c and daily insulin requirement were evident only after the first wave of the pandemic. CONCLUSIONS: This increase in HbA1c at diagnosis of type 1 diabetes during the Covid-19 pandemic may indicate a delay in seeking medical care due to the pandemic. However, this did not affect short-term glycemic control. The increased insulin requirement at follow-up could suggest a more rapid autoimmune progression during the pandemic.

Cataract in children and adolescents with type 1 diabetes. Insights from the German/Austrian DPV registry.

OBJECTIVE: To study diabetic cataract in type 1 diabetes in a large pediatric cohort. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Association of the use of diabetes technology with HbA1c and BMI-SDS in an international cohort of children and adolescents with type 1 diabetes: The SWEET project experience.

OBJECTIVE: To examine the association between the use of diabetes technology (insulin pump [CSII], glucose sensor [CGM] or both) and metabolic control (HbA1c) as well as body adiposity (BMI-SDS) over-time in a cohort of children and adolescents with type 1 diabetes (T1D), that have never used these technologies before. SUBJECTS AND METHODS: Four thousand six hundred forty three T1D patients (2-18 years, T1D ≥1 year, without celiac disease, no CSII and/or CGM before 2016) participating in the SWEET prospective multicenter diabetes registry, were enrolled. Data were collected at two points (2016; 2019). Metabolic control was assessed by glycated hemoglobin (HbA1c) and body adiposity by BMI-SDS (WHO). Patients were categorized by treatment modality (multiple daily injections [MDI] or CSII) and the use or not of CGM. Linear regression models, adjusted for age, gender, duration of diabetes and region, were applied to assess differences in HbA1c and BMI-SDS among patient groups. RESULTS: The proportion of patients using MDI with CGM and CSII with CGM significantly increased from 2016 to 2019 (7.2%-25.7%, 7.8%-27.8% respectively; p < 0.001). Linear regression models showed a significantly lower HbA1c in groups that switched from MDI to CSII with or without CGM (p < 0.001), but a higher BMI-SDS (from MDI without CGM to CSII with CGM p < 0.05; from MDI without CGM to CSII without CGM p < 0.01). CONCLUSIONS: Switching from MDI to CSII is significantly associated with improvement in glycemic control but increased BMI-SDS over-time. Diabetes technology may improve glucose control in youths with T1D although further strategies to prevent excess fat accumulation are needed.

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.

Diabetes in all hospitalized cases in Germany 2015-2019 and impact of the first COVID-19 year 2020.

Objective: To analyze the proportion of diabetes among all hospitalized cases in Germany between 2015 and 2020. Methods: Using the nationwide Diagnosis-Related-Groups statistics, we identified among all inpatient cases aged ≥ 20 years all types of diabetes in the main or secondary diagnoses based on ICD-10 codes, as well all COVID-19 diagnoses for 2020. Results: From 2015 to 2019, the proportion of cases with diabetes among all hospitalizations increased from 18.3% (3.01 of 16.45 million) to 18.5% (3.07 of 16.64 million). Although the total number of hospitalizations decreased in 2020, the proportion of cases with diabetes increased to 18.8% (2.73 of 14.50 million). The proportion of COVID-19 diagnosis was higher in cases with diabetes than in those without in all sex and age subgroups. The relative risk (RR) for a COVID-19 diagnosis in cases with vs without diabetes was highest in age group 40-49 years (RR in females: 1.51; in males: 1.41). Conclusions: The prevalence of diabetes in the hospital is twice as high as the prevalence in the general population and has increased further with the COVID-19 pandemic, underscoring the increased morbidity in this high-risk patient group. This study provides essential information that should help to better estimate the need for diabetological expertise in inpatient care settings.

Common procedures and conditions leading to inpatient hospital admissions in adults with and without diabetes from 2015 to 2019 in Germany : A comparison of frequency, length of hospital stay and complications.

OBJECTIVE: To evaluate common surgical procedures and admission causes in inpatient cases with diabetes in Germany between 2015 and 2019 and compare them to inpatient cases without diabetes. METHODS: Based on the German diagnosis-related groups (G-DRG) statistics, regression models stratified by age groups and gender were used to calculate hospital admissions/100,000 individuals, hospital days as well as the proportion of complications and mortality in inpatient cases ≥ 40 years with or without a documented diagnosis of diabetes (type 1 or type 2). RESULTS: A total of 14,222,326 (21%) of all inpatient cases aged ≥ 40 years had a diagnosis of diabetes. More middle-aged females with vs. without diabetes/100,000 individuals [95% CI] were observed, most pronounced in cases aged 40-< 50 years with myocardial infarction (305 [293-319] vs. 36 [36-37], p < 0.001). Higher proportions of complications and longer hospital stays were found for all procedures and morbidities in cases with diabetes. CONCLUSION: Earlier hospitalizations, longer hospital stays and more complications in inpatient cases with diabetes together with the predicted future increase in diabetes prevalence depict huge challenges for the German healthcare system. There is an urgent need for developing strategies to adequately care for patients with diabetes in hospital.

Area deprivation and demographic factors associated with diabetes technology use in adults with type 1 diabetes in Germany.

Introduction: Diabetes technology improves glycemic control and quality of life for many people with type 1 diabetes (T1D). However, inequalities in access to diabetes technology exist in many countries. In Germany, disparities in technology use have been described in pediatric T1D, but no data for adults are available so far. We therefore aimed to analyze whether demographic factors and area deprivation are associated with technology use in a representative population of adults with T1D. Materials and methods: In adults with T1D from the German prospective diabetes follow-up registry (DPV), we analyzed the use of continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), and sensor augmented pump therapy (SAP, with and without automated insulin delivery) in 2019-2021 by age group, gender, migration background, and area deprivation using multiple adjusted regression models. Area deprivation, defined as a relative lack of area-based resources, was measured by quintiles of the German index of Multiple Deprivation (GIMD 2015, from Q1, least deprived, to Q5, most deprived districts). Results: Among 13,351 adults with T1D, the use of technology decreased significantly with older age: CSII use fell from 56.1% in the 18-<25-year age group to 3.1% in the ≥80-year age group, CGM use from 75.3% to 28.2%, and SAP use from 45.1% to 1.5% (all p for trend <0.001). The use of technology was also significantly higher in women than in men (CSII: 39.2% vs. 27.6%; CGM: 61.9% vs. 58.0%; SAP: 28.7% vs. 19.6%, all p <0.001), and in individuals without migration background than in those with migration background (CSII: 38.8% vs. 27.6%; CGM: 71.1% vs. 61.4%; SAP: 30.5% vs. 21.3%, all p <0.001). Associations with area deprivation were not linear: the use of each technology decreased only from Q2 to Q4. Discussion: Our real-world data provide evidence that higher age, male gender, and migration background are currently associated with lower use of diabetes technology in adults with T1D in Germany. Associations with area deprivation are more complex, probably due to correlations with other factors, like the higher proportion of migrants in less deprived areas or the federal structure of the German health care system.

Impact of Newborn Screening on Adult Height in Patients With Congenital Adrenal Hyperplasia (CAH).

CONTEXT: Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening. DESIGN: Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively. PATIENTS AND METHODS: We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone.To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4). RESULTS: TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [-0.25 standard deviation score (SDS); -0.44 to -0.06] than in patients without newborn screening (-0.44 SDS; -0.52 to -0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; -0.28-0.59) than without screening (-0.35 SDS; -0.52 to -0.18). CONCLUSIONS: Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.

Posttraumatic stress disorder and diabetes-related outcomes in patients with type 1 diabetes.

Mental comorbidities in patients with type 1 diabetes mellitus (T1D) are common, and can have a negative impact on acute blood glucose levels and long-term metabolic control. Information on the association of T1D and comorbid posttraumatic stress disorder (PTSD) with diabetes-related outcomes is limited. The aim was to examine the associations between a clinical diagnosis of PTSD and diabetes-related outcomes in patients with T1D. Patients with T1D and comorbid documented PTSD from the DPV database (n = 179) were compared to a group with T1D without PTSD (n = 895), and compared to a group with T1D without comorbid mental disorder (n = 895) by matching demographics (age, gender, duration of diabetes, therapy and migration background) 1:5. Clinical diabetes-related outcomes {body mass index (BMI), hemoglobin A1c (hbA1c), daily insulin dose, diabetic ketoacidosis (DKA), hypoglycemia, number of hospital admissions, number of hospital days} were analyzed, stratified by age groups (≤ 25 years vs. > 25 years). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD or patients without mental disorders had significantly higher HbA1c (8.71 vs. 8.30 or 8.24%), higher number of hospital admissions (0.94 vs. 0.44 or 0.32 per year) and higher rates of DKA (0.10 vs. 0.02 or 0.01 events/year). Patients with comorbid PTSD aged ≤ 25 years compared with patients without PTSD had significantly higher BMI (0.85 vs. 0.59) and longer hospital stays (15.89 vs.11.58 days) than patients without PTSD. Patients with PTSD > 25 years compared with patients without PTSD or without any mental comorbidities had significantly fewer hospital admissions (0.49 vs. 0.77 or 0.69), but a longer hospital length of stay (20.35 vs. 11.58 or 1.09 days). We found that PTSD in younger patients with T1D is significantly related to diabetes outcome. In adult patients with T1D, comorbid PTSD is associated with fewer, but longer hospitalizations. Awareness of PTSD in the care of patients with T1D should be raised and psychological intervention should be provided when necessary.

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation.

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation.

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.

Fasting indices of glucose-insulin-metabolism across life span and prediction of glycemic deterioration in children with obesity from new diagnostic cut-offs.

Background: Fasting indices of glucose-insulin-metabolism are an easy and affordable tool to assess insulin resistance. We aimed to establish reference ranges for fasting insulin indices that reflect age-dependent variation over the entire life span and subsequently test their clinical application regarding the prediction of glycemic deterioration in children. Methods: We calculated age- and puberty-dependent reference values for HOMA-IR, HOMA2-IR, HOMA-ß, McAuley index, fasting insulin, and fasting glucose from 6994 observations of 5512 non-obese healthy subjects aged 5-80 years. Applying those references, we determined the prevalence of insulin resistance among 2538 subjects with obesity. Furthermore, we investigated the intraindividual stability and the predictive values for future dysglycemia of these fasting indices in 516 children and adolescents with obesity up to 19 years of follow-up. We validated the results in three independent cohorts. Findings: There was a strong age-dependent variation of all indices throughout the life span, including prolonged recovery of pubertal insulin resistance and a subsequent continuous increase throughout adulthood. Already from age 5 years onwards, >40% of children with obesity presented with elevated parameters of insulin resistance. Applying newly developed reference ranges, insulin resistance among children with obesity doubled the risk for future glycemic deterioration (HOMA-IR HR 1.88 (95% CI 1.1-3.21)), fasting insulin HR 1.89 (95% CI 1.11-3.23). In contrast, fasting glucose alone was not predictive for emerging dysglycemia in children with obesity (HR 1.03 (95% CI 0.62-1.71)). The new insulin-based thresholds were superior to fasting glucose and HbA1c in detecting children eventually manifesting with dysglycemia in prospective analyses. Interpretation: The variation of fasting glucose-insulin-metabolism across the life span necessitates age-specific reference ranges. The improved prediction of future glycemic deterioration by indices based on fasting insulin beyond simple glucose measures alone could help to stratify risk characteristics of children with obesity in order to guide patient-tailored prevention and intervention approaches. Funding: German Research Foundation (DFG)-through SFB 1052, project number 209933838, subproject C5; Federal Ministry of Education and Research, Germany; European Union-European Regional Development Fund; Free State of Saxony. The German Diabetes Association, the CarbHealth consortium (01EA1908B). EU-IMI2-Consortium SOPHIA (grant agreement No 875534), German Center for Diabetes Research (DZD), grant number 82DZD14E03.

Idiopathic Frozen Shoulder in Individuals with Diabetes: Association with Metabolic Control, Obesity, Antidiabetic Treatment and Demographic Characteristics in Adults with Type 1 or 2 Diabetes from the DPV Registry.

AIMS: To examine the association of frozen shoulder (FS) with demographic and diabetes-related outcomes in individuals with type 1 (T1D) or type 2 (T2D) diabetes aged ≥30 years. MATERIALS AND METHODS: Multivariable logistic regression models, adjusted for demographics were used to calculate the proportion of FS in association with age, gender, diabetes duration, body mass index (BMI), haemoglobin A1C (HbA1c) and diabetes treatment. RESULTS: The unadjusted percentage of FS was higher in T1D compared to T2D (0.22% vs. 0.06%). In T1D, adjusted regression models revealed higher prevalence of FS in women than men (0.26 [0.20-0.34] % vs. 0.15 [0.11-0.21] %, p=0.010). No significant relationship of age and BMI with FS was found in both diabetes types. Longer diabetes duration was associated with a higher proportion of FS in T1D (p<0.001) and T2D (p=0.004). In T1D, HbA1c >7% was related to a higher proportion of FS compared to HbA1c ≤7% (0.25 [0.19-0.32] vs. 0.12 [0.08-0.20] %, p=0.007), while an inverse relationship was found in T2D (HbA1c ≤7%: 0.08 [0.07-0.10] vs. HbA1c >7%: 0.05 [0.04-0.06] %, p=0.001). CONCLUSIONS: Different associations of FS with gender and HbA1c were observed for T1D and T2D; however, longer diabetes duration increases the risk for FS independent of diabetes type. Musculoskeletal diseases are still underreported in individuals with diabetes and awareness should be raised for FS as a specific diabetes complication.

Incidence of Type 1 Diabetes in Children and Adolescents During the COVID-19 Pandemic in Germany: Results From the DPV Registry.

OBJECTIVE: The aim of this study was to investigate the incidence of type 1 diabetes in children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with previous years. RESEARCH DESIGN AND METHODS: Based on data from the multicenter German Diabetes Prospective Follow-up Registry, we analyzed the incidence of type 1 diabetes per 100,000 patient-years in children and adolescents from 1 January 2020 through 30 June 2021. Using Poisson regression models, expected incidences for 2020/21 were estimated based on the data from 2011 to 2019 and compared with observed incidences in 2020/21 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS: From 1 January 2020 to 30 June 2021, 5,162 children and adolescents with new-onset type 1 diabetes in Germany were registered. The observed incidence in 2020/21 was significantly higher than the expected incidence (24.4 [95% CI 23.6-25.2] vs. 21.2 [20.5-21.9]; IRR 1.15 [1.10-1.20]; P < 0.001). IRRs were significantly elevated in June 2020 (IRR 1.43 [1.07-1.90]; P = 0.003), July 2020 (IRR 1.48 [1.12-1.96]; P < 0.001), March 2021 (IRR 1.29 [1.01-1.65]; P = 0.028), and June 2021 (IRR 1.39 [1.04-1.85]; P = 0.010). CONCLUSIONS: A significant increase in the incidence of type 1 diabetes in children was observed during the COVID-19 pandemic, with a delay in the peak incidence of type 1 diabetes by ∼3 months after the peak COVID-19 incidence and also after pandemic containment measures. The underlying causes are yet unknown. However, indirect rather than direct effects of the pandemic are more likely to be the cause.

Twenty years of newborn screening for congenital adrenal hyperplasia and congenital primary hypothyroidism - experiences from the DGKED/AQUAPE study group for quality improvement in Germany.

Congenital primary hypothyroidism (CH) and congenital adrenal hyperplasia (CAH) are targeted by the German and Austrian newborn screening. For both diseases, there are registries for quality improvement, based on standardized observational data from long-term patient follow-up, under the auspices of the DGKED study group. By September 2021, the CH registry HypoDOK includes datasets from 23,348 visits of 1,840 patients, and the CAH registry contains datasets from 36,237 visits of 1,976 patients. Here, we report on the recruitment process, patient characteristics, and research contributions from the registries, and underline that the registries are an important tool to improve patient care and outcomes. Registries for rare conditions should thus be considered as an important public health measure and they should be adequately institutionalized and funded.

Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries.

BACKGROUND: An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic. METHODS: For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker. FINDINGS: 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p<0·0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1·037 (95% CI 1·024 to 1·051; p<0·0001) per ten-unit increase in the Stringency Index for 2020 and 1·028 (1·009 to 1·047; p=0·0033) for 2021, but was not significantly associated with excess all-cause mortality. INTERPRETATION: During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents. FUNDING: German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.

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).

The Association between Treatment Modality, Lipid Profile, Metabolic Control in Children with Type 1 Diabetes and Celiac Disease-Data from the International Sweet Registry.

BACKGROUND AND AIMS: A higher frequency of dyslipidemia is reported in children with type 1 diabetes (T1D) and celiac disease (CD). Recently, continuous subcutaneous insulin infusion (CSII) has been associated with better lipid profiles in patients with T1D. The aim of this study was to investigate the association between treatment modality and lipid profile, metabolic control, and body mass index (BMI)-SDS in children with both T1D and CD. METHODS: Cross-sectional study in children registered in the international SWEET database in November 2020. Inclusion criteria were children (2-18 years) with T1D and CD with available data on treatment modality (CSII and injections therapy, IT), triglyceride, total cholesterol, HDL, LDL, dyslipidemia, HbA1c, and BMI-SDS. Overweight/obesity was defined as > +1 BMI-SDS for age. Data were analyzed by linear and logistical regression models with adjustment for age, gender, and diabetes duration. RESULTS: In total 1009 children with T1D and CD (female 54%, CSII 54%, age 13.9 years ±3.6, diabetes duration 7.2 years ±4.1, HbA1c 7.9% ±1.4) were included. Significant differences between children treated with CSII vs. IT were respectively found; HDL 60.0 mg/dL vs. 57.8 mg/dL, LDL 89.4 mg/dL vs. 94.2 mg/dL, HbA1c 7.7 vs. 8.1%, BMI-SDS 0.4 vs. 0.6, overweight and obesity 17% vs. 26% (all p < 0.05). CONCLUSIONS: CSII is associated with higher HDL and lower LDL, HbA1c, BMI-SDS, and percentage of overweight and obesity compared with IT in this study. Further prospective studies are required to determine whether CSII improves lipid profile, metabolic control and normalize body weight in children with both T1D and CD.

Incidence of COVID-19 and Risk of Diabetic Ketoacidosis in New-Onset Type 1 Diabetes.

OBJECTIVES: With this study, our aim was to quantify the relative risk (RR) of diabetic ketoacidosis at diagnosis of type 1 diabetes during the year 2020 and to assess whether it was associated with the regional incidence of coronavirus disease 2019 (COVID-19) cases and deaths. METHODS: Multicenter cohort study based on data from the German Diabetes Prospective Follow-up Registry. The monthly RR for ketoacidosis in 2020 was estimated from observed and expected rates in 3238 children with new-onset type 1 diabetes. Expected rates were derived from data from 2000 to 2019 by using a multivariable logistic trend regression model. The association between the regional incidence of COVID-19 and the rate of ketoacidosis was investigated by applying a log-binomial mixed-effects model to weekly data with Germany divided into 5 regions. RESULTS: The observed versus expected frequency of diabetic ketoacidosis was significantly higher from April to September and in December (mean adjusted RRs, 1.48-1.96). During the first half of 2020, each increase in the regional weekly incidence of COVID-19 by 50 cases or 1 death per 100 000 population was associated with an increase in the RR of diabetic ketoacidosis of 1.40 (95% confidence interval, 1.10-1.77; P = .006) and 1.23 (1.14-1.32; P < .001), respectively. This association was no longer evident during the second half of 2020. CONCLUSIONS: These findings suggest that the local severity of the pandemic rather than health policy measures appear to be the main reason for the increase in diabetic ketoacidosis and thus the delayed use of health care during the pandemic.