Risk perception, well-being, depression and anxiety in children and adolescents with rheumatic diseases during the COVID-19 pandemic - results from the prospective multicenter KICK-COVID study in Germany.

OBJECTIVE: To investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic. METHODS: As part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents < 21 years and parents of children < 12 years with rheumatic diseases answered questions on perceptions of health risk (PHR) due to SARS-CoV2, stress, well-being (WHO-5) and symptoms of depression (PHQ-9) and anxiety (GAD-7). Data were collected at routine visits from June to December 2021 and assessed for association with demographic and clinical parameters, treatment and patient-reported outcomes by multivariable regression analyses. RESULTS: Data from 1356 individuals (69% female, 50% adolescents) were included. Median PHR on a numeric rating scale (NRS, 0-10) was 4 (IQR 2-6), median perceived stress was 3 (IQR 1-6). Adolescents reported a worse well-being with a significantly lower median WHO-5-score (60, IQR 40-76) than parents reported for their children < 12 years (80, IQR 68-84). Moderate to severe symptoms of depression and anxiety were reported by 14.3% and 12.3% of the adolescents, respectively. PHR was significantly higher in patients with systemic lupus erythematosus, methotrexate or biologic disease-modifying anti-rheumatic drug therapy than in patients without these characteristics, whereas lower WHO-5 or higher PHQ-9 or GAD-7 scores were only associated with poorer patient-reported health status and physical functioning. CONCLUSION: The perception of health risk due to SARS-CoV2 infection was not paralleled by an impairment of mental health, which were, however, significantly correlated with self-rated health status and functional capacity, highlighting the importance of patient-reported outcome assessment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

The role of sex on the prevalence of cardiovascular risk factors in children and adolescents with Type 1 diabetes: The SWEET international database.

OBJECTIVE: To assess the prevalence of cardiovascular risk factors (CVRFs) in children and adolescents with type 1 diabetes (T1D) in the International SWEET registry and the possible role of clinical variables in modifying the risk of having single or multiple CVRFs. STUDY DESIGN: The study is a cross-sectional study. Cut-off points for CVRFs were fixed according to International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines and WHO parameters: LDL cholesterol (LDL-C) > 100 mg/dL; Systolic Blood Pressure (BP-SDS) > 90th percentile for sex, age, and height; BMI-SDS > 2SD for sex and age. Logistic regression models were applied to evaluate variables associated with at least 1 or 2 CVRFs among registry children and adolescents. RESULTS: 29,649 individuals with T1D (6-18 years, T1D ≥ 2 years) participating in the SWEET prospective multicenter diabetes registry were included. In the cohort, 41 % had one or more CVRFs, and 10 % had two or more CVRFs. Thirty-five percent of enrolled individuals had LDL-C > 100 mg/dL, 26 % had BMI-SDS > 2SD, and 17 % had Systolic BP-SDS > 90th percentile. Females had higher frequency than males of having 1 or 2 CVRFs (45.1 % vs 37.4 %, 11.8 % vs 7.8 %; p < 0.001). Multivariable logistic regression models showed that sex (female), HbA1c category (>7.0 %), and age (>10 years) were associated with a higher chance of having at least 1 or 2 CVRFs (p < 0.001). CONCLUSIONS: In children and adolescents with T1D, female sex, in addition to HbA1c above 7 %, and older age (>10 years) was associated with a higher risk of having at least a CVRF (LDL-C, BMI-SDS, BP) according to internationally defined cut-offs.

Psychosocial Burden During the COVID-19 Pandemic in Adolescents With Type 1 Diabetes in Germany and Its Association With Metabolic Control.

PURPOSE: To investigate the psychosocial burden during the COVID-19 pandemic in adolescents with type 1 diabetes and its association with metabolic control. METHODS: Prospective multicenter observational cohort study based on data from the German Diabetes Prospective Follow-up Registry. Adolescents aged 12-20 years with type 1 diabetes were asked during routine follow-up visits to complete a questionnaire on psychosocial distress and daily use of electronic media during the COVID-19 pandemic from June 2021 to November 2022. Well-being, anxiety, and depression symptoms were assessed using World Health Organization Five Well-Being Index (WHO-5), General Anxiety Disorder scale 7 (GAD-7), and Patient Health Questionnaire-9 questionnaires. The impact of mental health symptoms on metabolic control was analyzed by using multivariable linear regression models adjusted for sex, diabetes duration, treatment, socioeconomic deprivation, and immigrant background. RESULTS: Six hundred eighty eight adolescents (45.6% females) from 20 diabetes centers participated. Compared with a prepandemic cohort, WHO-5 scores were lower during the COVID-19 pandemic (estimated mean difference -9.6 [95% confidence interval -11.6; -7.6], p < .001), but GAD-7 scores were not different (estimated mean difference 0.6 [95% confidence interval -0.2; 1.5], p = .14). HbA1c was significantly positively associated with GAD-7 and Patient Health Questionnaire-9 and negatively associated with WHO-5 scores (all p < .001). Daily electronic media use was positively associated with adjusted mental health symptoms (all p < .01). DISCUSSION: Although the overall well-being of adolescents with type 1 diabetes was reduced during the later phase of the COVID-19 pandemic, the additional psychological burden was relatively low. However, mental health symptoms were associated with poorer metabolic control and higher use of electronic media.

Demographic, Clinical, Management, and Outcome Characteristics of 8,004 Young Children With Type 1 Diabetes.

OBJECTIVE: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes age <6 years across three international registries: Diabetes Prospective Follow-Up Registry (DPV; Europe), T1D Exchange Quality Improvement Network (T1DX-QI; U.S.), and Australasian Diabetes Data Network (ADDN; Australasia). RESEARCH DESIGN AND METHODS: An analysis was conducted comparing 2019-2021 prospective registry data from 8,004 children. RESULTS: Mean ± SD ages at diabetes diagnosis were 3.2 ± 1.4 (DPV and ADDN) and 3.7 ± 1.8 years (T1DX-QI). Mean ± SD diabetes durations were 1.4 ± 1.3 (DPV), 1.4 ± 1.6 (T1DX-QI), and 1.5 ± 1.3 years (ADDN). BMI z scores were in the overweight range in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN) of participants. Mean ± SD HbA1c varied among registries: DPV 7.3 ± 0.9% (56 ± 10 mmol/mol), T1DX-QI 8.0 ± 1.4% (64 ± 16 mmol/mol), and ADDN 7.7 ± 1.2% (61 ± 13 mmol/mol). Overall, 37.5% of children achieved the target HbA1c of <7.0% (53 mmol/mol): 43.6% in DPV, 25.5% in T1DX-QI, and 27.5% in ADDN. Use of diabetes technologies such as insulin pump (DPV 86.6%, T1DX 46.6%, and ADDN 39.2%) and continuous glucose monitoring (CGM; DPV 85.1%, T1DX-QI 57.6%, and ADDN 70.5%) varied among registries. Use of hybrid closed-loop (HCL) systems was uncommon (from 0.5% [ADDN] to 6.9% [DPV]). CONCLUSIONS: Across three major registries, more than half of children age <6 years did not achieve the target HbA1c of <7.0% (53 mmol/mol). CGM was used by most participants, whereas insulin pump use varied across registries, and HCL system use was rare. The differences seen in glycemia and use of diabetes technologies among registries require further investigation to determine potential contributing factors and areas to target to improve the care of this vulnerable group.

Time trends towards earlier puberty in boys and girls with type 1 diabetes: Insights from the German Diabetes Prospective Follow-up (DPV) registry, 2000 to 2021.

AIM: To examine the time trends and factors associated with the onset of puberty in children with type 1 diabetes (T1D) using data from the German Diabetes Prospective Follow-up (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry. METHODS: A total of 13 127 children with T1D, aged 6 to 18 years, were included in the analysis. Regression analysis was performed to investigate the relationship between diabetes duration, body mass index (BMI) standard deviation score (SDS), glycated haemoglobin (HbA1c) level, migration background, and the onset of puberty, stratified by sex. RESULTS: Our findings revealed a significant trend towards earlier puberty in both girls and boys with T1D over the observed period (2000 to 2021). Puberty onset in girls (thelarche Tanner stage B2) decreased from 11.48 (11.35-11.65) years in 2000 to 10.93 (10.79-11.08) years in 2021 and gonadarche (Tanner stage G2/testicular volume >3 mL) decreased from 12.62 (12.42-12.82) years in 2000 to 11.98 (11.79-12.16) years in 2021 in boys (both P < 0.001). Longer diabetes duration, higher BMI SDS, and lower HbA1c level were associated with earlier puberty in both sexes (P < 0.001). CONCLUSIONS: Our study highlights earlier puberty in children with T1D, influenced by BMI SDS, HbA1c level, and migration background. This has important implications for diabetes management and supporting healthy development. Further research is needed to understand the underlying mechanisms and develop potential interventions for this vulnerable population.

Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity.

OBJECTIVE: The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. METHODS: Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7-13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79-2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. RESULTS: A total of 36.3% of children and adolescents experienced "no BMIz loss." The largest subcluster (44.8%) achieved "moderate BMIz loss," with an average delta-BMIz of -0.23 (IQR: -0.33 to -0.14) at study end. A total of 18.9% had a "pronounced BMIz loss" up to -0.61 (IQR: -0.76 to -0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). CONCLUSIONS: These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success.

Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.

BACKGROUND: Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). METHODS AND RESULTS: Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF. CONCLUSION: These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.

Diabetes care practices and outcomes in 40.000 children and adolescents with type 1 diabetes from the SWEET registry during the COVID-19 pandemic.

AIMS: This study aimed to provide a global insight into initiatives in type 1 diabetes care driven by the COVID-19 pandemic and associations with glycemic outcomes. METHODS: An online questionnaire regarding diabetes care before and during the pandemic was sent to all centers (n = 97, 66,985 youth with type 1 diabetes) active in the SWEET registry. Eighty-two responded, and 70 (42,798 youth with type 1 diabetes) had available data (from individuals with type 1 diabetes duration >3 months, aged ≤21 years) for all 4 years from 2018 to 2021. Statistical models were adjusted, among others, for technology use. RESULTS: Sixty-five centers provided telemedicine during COVID-19. Among those centers naive to telemedicine before the pandemic (n = 22), four continued only face-to-face visits. Centers that transitioned partially to telemedicine (n = 32) showed a steady increase in HbA1c between 2018 and 2021 (p < 0.001). Those that transitioned mainly to telemedicine (n = 33 %) improved HbA1c in 2021 compared to 2018 (p < 0.001). CONCLUSIONS: Changes to models of care delivery driven by the pandemic showed significant associations with HbA1c shortly after the pandemic outbreak and 2 years of follow-up. The association appeared independent of the concomitant increase in technology use among youth with type 1 diabetes.

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

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

Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm.

AIM: To identify predictive factors for diabetic ketoacidosis (DKA) by retrospective analysis of registry data and the use of a subgroup discovery algorithm. MATERIALS AND METHODS: Data from adults and children with type 1 diabetes and more than two diabetes-related visits were analysed from the Diabetes Prospective Follow-up Registry. Q-Finder, a supervised non-parametric proprietary subgroup discovery algorithm, was used to identify subgroups with clinical characteristics associated with increased DKA risk. DKA was defined as pH less than 7.3 during a hospitalization event. RESULTS: Data for 108 223 adults and children, of whom 5609 (5.2%) had DKA, were studied. Q-Finder analysis identified 11 profiles associated with an increased risk of DKA: low body mass index standard deviation score; DKA at diagnosis; age 6-10 years; age 11-15 years; an HbA1c of 8.87% or higher (≥ 73 mmol/mol); no fast-acting insulin intake; age younger than 15 years and not using a continuous glucose monitoring system; physician diagnosis of nephrotic kidney disease; severe hypoglycaemia; hypoglycaemic coma; and autoimmune thyroiditis. Risk of DKA increased with the number of risk profiles matching patients' characteristics. CONCLUSIONS: Q-Finder confirmed common risk profiles identified by conventional statistical methods and allowed the generation of new profiles that may help predict patients with type 1 diabetes who are at a greater risk of experiencing DKA.

A prospective analysis of the long-term impact of the COVID-19 pandemic on well-being and health care among children with a chronic condition and their families: a study protocol of the KICK-COVID study.

BACKGROUND: There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents. METHODS: We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample. DISCUSSION: The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Clinical characteristics, treatment patterns, and persistence in individuals with type 2 diabetes initiating a glucagon-like peptide-1 receptor agonist: A retrospective analysis of the Diabetes Prospective Follow-Up Registry.

AIMS: To describe clinical characteristics, treatment patterns and glucagon-like peptide-1 receptor agonist (GLP-1 RA) persistence in individuals with type 2 diabetes (T2D) initiating their first GLP-1 RA. MATERIALS AND METHODS: A real-world analysis of adults with T2D initiating GLP-1 RA therapy between 2007 and June 2020 from the multicentre Diabetes Prospective Follow-Up (DPV) Registry, stratified by antidiabetes therapy at the time of GLP-1 RA initiation: oral antidiabetic drugs (OAD), insulin ± OAD or lifestyle modification (LM). GLP-1 RA treatment persistence in individuals with ≥12 months follow-up was determined by Kaplan-Meier analysis. RESULTS: Overall, 15 111 individuals with T2D initiating GLP-1 RA therapy (55% men) were identified; median [interquartile range (IQR)] age [58.7 (50.6-66.7) years], diabetes duration [8.5 (3.6-14.7) years], glycated haemoglobin [HbA1c; 8.2 (7.1-9.8)%]. Median (95% confidence interval) GLP-1 RA persistence in eligible individuals (n = 5189) was 11 (10-12) months; OAD 12 (11-14) months (n = 2453); insulin ± OAD 11 (9-12) months (n = 2204); and LM 7 (5-9) months (n = 532). Median treatment persistence tended to increase from 2007-2012 to 2017-2020. Median (IQR) HbA1c decreased from baseline [8.2 (7.1-9.8)%] to discontinuation [7.5 (6.6-8.7)%], with a greater decrease observed in individuals with persistence >12 months versus ≤12 months. Individuals who discontinued GLP-1 RA therapy predominantly switched to insulin (if not already using) or dipeptidyl peptidase-4 inhibitors. CONCLUSION: Real-world registry data revealed improved outcomes with longer median GLP-1 RA persistence; ~50% of patients overall achieved HbA1c <7% at 12 months. Persistence was highest with baseline OAD and/or insulin, and tended to increase over the period 2007-2020.

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.

Association of Achieving Time in Range Clinical Targets With Treatment Modality Among Youths With Type 1 Diabetes.

Importance: Continuous glucose monitoring (CGM) devices have demonstrated efficacy in adults and more recently in youths and older adults with type 1 diabetes. In adults with type 1 diabetes, the use of real-time CGM compared with intermittently scanned CGM was associated with improved glycemic control, but there are limited data available for youths. Objective: To assess real-world data on achievement of time in range clinical targets associated with different treatment modalities in youths with type 1 diabetes. Design, Setting, and Participants: This multinational cohort study included children, adolescents, and young adults younger than 21 years (hereinafter referred to collectively as youths) with type 1 diabetes for a duration of at least 6 months who provided CGM data between January 1, 2016, and December 31, 2021. Participants were enrolled from the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) registry. Data from 21 countries were included. Participants were divided into 4 treatment modalities: intermittently scanned CGM with or without insulin pump use and real-time CGM with or without insulin pump use. Exposures: Type 1 diabetes and the use of CGM with or without an insulin pump. Main Outcomes and Measures: Proportion of individuals in each treatment modality group achieving recommended CGM clinical targets. Results: Among the 5219 participants (2714 [52.0%] male; median age, 14.4 [IQR, 11.2-17.1] years), median duration of diabetes was 5.2 (IQR, 2.7-8.7) years and median hemoglobin A1c level was 7.4% (IQR, 6.8%-8.0%). Treatment modality was associated with the proportion of individuals achieving recommended clinical targets. Adjusted for sex, age, diabetes duration, and body mass index standard deviation score, the proportion achieving the recommended greater than 70% time in range target was highest with real-time CGM plus insulin pump use (36.2% [95% CI, 33.9%-38.4%]), followed by real-time CGM plus injection use (20.9% [95% CI, 18.0%-24.1%]), intermittently scanned CGM plus injection use (12.5% [95% CI, 10.7%-14.4%]), and intermittently scanned CGM plus insulin pump use (11.3% [95% CI, 9.2%-13.8%]) (P < .001). Similar trends were observed for less than 25% time above (real-time CGM plus insulin pump, 32.5% [95% CI, 30.4%-34.7%]; intermittently scanned CGM plus insulin pump, 12.8% [95% CI, 10.6%-15.4%]; P < .001) and less than 4% time below range target (real-time CGM plus insulin pump, 73.1% [95% CI, 71.1%-75.0%]; intermittently scanned CGM plus insulin pump, 47.6% [95% CI, 44.1%-51.1%]; P < .001). Adjusted time in range was highest among real-time CGM plus insulin pump users (64.7% [95% CI, 62.6%-66.7%]). Treatment modality was associated with the proportion of participants experiencing severe hypoglycemia and diabetic ketoacidosis events. Conclusions and Relevance: In this multinational cohort study of youths with type 1 diabetes, concurrent use of real-time CGM and an insulin pump was associated with increased probability of achieving recommended clinical targets and time in range target as well as lower probability of severe adverse events compared with other treatment modalities.

Empagliflozin cardiovascular and renal effectiveness and safety compared to dipeptidyl peptidase-4 inhibitors across 11 countries in Europe and Asia: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

BACKGROUND: Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with type 2 diabetes compared to similar therapies. METHODS: The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014-2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined. FINDINGS: Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions. INTERPRETATION: Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.

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

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

Spatiotemporal association between COVID-19 incidence and type 1 diabetes incidence among children and adolescents: a register-based ecological study in Germany.

Objective: Studies have shown an increased incidence of pediatric type 1 diabetes during the COVID-19 pandemic, but the detailed role of SARS-CoV-2 infection in the incidence increase in type 1 diabetes remains unclear. We investigated the spatiotemporal association of pediatric type 1 diabetes and COVID-19 incidence at the district level in Germany. Methods: For the period from March 2020 to June 2022, nationwide data on incident type 1 diabetes among children and adolescents aged <20 years and daily documented COVID-19 infections in the total population were obtained from the German Diabetes Prospective Follow-up Registry and the Robert Koch Institute, respectively. Data were aggregated at district level and seven time periods related to COVID-19 pandemic waves. Spatiotemporal associations between indirectly standardized incidence rates of type 1 diabetes and COVID-19 were analyzed by Spearman correlation and Bayesian spatiotemporal conditional autoregressive Poisson models. Results: Standardized incidence ratios of type 1 diabetes and COVID-19 in the pandemic period were not significantly correlated across districts and time periods. A doubling of the COVID-19 incidence rate was not associated with a significant increase in the incidence rate of type 1 diabetes (relative risk 1.006, 95% CI 0.987; 1.019). Conclusion: Our findings based on data from the pandemic period indirectly indicate that a causal relationship between SARS-COV-2 infection and type 1 diabetes among children and adolescents is unlikely.

Diabetes-related antibody-testing is a valuable screening tool for identifying monogenic diabetes - A survey from the worldwide SWEET registry.

AIMS: To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes. METHODS: 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing. RESULTS: 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome. CONCLUSIONS: Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management. TRIAL REGISTRATION: NCT04427189.

The COVID-19 Pandemic Affects Seasonality, With Increasing Cases of New-Onset Type 1 Diabetes in Children, From the Worldwide SWEET Registry.

OBJECTIVE: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. RESEARCH DESIGN AND METHODS: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. RESULTS: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1-12.2) in 2018 to 21.7 (20.6-22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2-14.0) in 2018 to 26.7 (25.7-27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5-12.9) to 24.7 (24.0-25.5) for adolescents ages 12-18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018-2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic. CONCLUSIONS: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent.

A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes.

AIMS: (1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA). METHODS: The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration. RESULTS: Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2 years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4 years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64 mmol/mol versus 7.96%, 63 mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI - 0.08, 0.25)]. FBG was 9.37 mmol/L (168.9 mg/dL) and 9.58 mmol/L (172.6 mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. - 0.21; (95%CI - 1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI - 1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant. CONCLUSIONS: Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.