Stefanie Lanzinger

Background: Whether socioeconomic status (SES) influences obesity treatment response among children remains unclear. This study aimed to examine the association between SES and response to health behavior and lifestyle pediatric obesity treatment over 3 years in two European countries. Methods and findings: In this two-cohort study, data were obtained from the Swedish Childhood Obesity Treatment Register (BORIS) and the German/Austrian/Swiss Adiposity Patients Register (APV). SES was divided into quintiles, using individual-level indicators as a composite index in Sweden and an area-level index in Germany. Treatment response was assessed as change in body mass index standard deviation score (BMI SDS) using linear mixed-effects models, obesity remission using Cox regression, and treatment discontinuation within six months using mixed-effects logistic regression. Analyses were stratified by country and adjusted for sex, baseline obesity class, age group, and migration background. Among 45,804 children with obesity who received health behavior and lifestyle obesity treatment, 31,293 (18,588 in Sweden and 12,705 in Germany) received at least six months of treatment. In both countries, higher baseline BMI SDS was associated with lower SES, p = 0.143). In Germany, higher SES was associated with greater reductions in BMI SDS ( p < 0.001), with the largest decreases observed in the highest SES quintile after 2 years of treatment, −0.36 (95% CI [−0.38, −0.34]), sustained at 3 years (−0.34, 95% CI [−0.38, −0.29]). The difference in BMI SDS reduction between the highest and the lowest SES was greatest after 2 years, −0.12 (95% CI [−0.13, −0.12]) than after 3 years, −0.05 (95% CI [−0.07, −0.03]). Obesity remission showed a socioeconomic gradient in both countries, with higher adjusted probabilities in the highest versus lowest SES quintile (Sweden: 0.49 versus 0.37; Germany: 0.53 versus 0.45), corresponding to rate ratios of 1.63 (95% CI [1.44, 1.86]; p < 0.001) and 1.35 (95% CI [1.22, 1.50]; p < 0.001), respectively. Treatment discontinuation also differed by country. In Germany, higher SES compared to the lowest SES was associated with lower odds of discontinuation,OR of 0.82 (95% CI [0.74, 0.90]; p < 0.001), whereas no association was observed in Sweden. Residual confounding due to unavailable clinical and familial characteristics could not be ruled out. Conclusions: SES was associated with pediatric obesity treatment outcomes, but patterns differed between countries. While socioeconomic gradients in remission were observed in both settings, inequalities in BMI SDS reduction and treatment discontinuation were evident only in Germany, pointing to potential roles of both measurement differences and contextual factors.

Aims: To test the hypothesis that continuous glucose monitoring (CGM) metrics are independently associated with cardiovascular risk factor (CVRF) exposure, particularly low‐density lipoprotein cholesterol (LDL‐C) and blood pressure (BP), in youth with type 1 diabetes (T1D) enrolled in the international SWEET registry. Materials and Methods: This cross‐sectional study included youth aged 6–18 years with T1D duration ≥ 1 year, not receiving antihypertensive or lipid‐lowering therapy and with available CGM profiles (≥ 14 days), lipid and BP data between January 2019 and June 2023. Associations between CGM metrics and LDL‐C or BP were analysed using multiple linear regression, adjusted for sex and pubertal status (model 1) and additionally for body mass index–SDS (model 2), diabetes duration (model 3) and HbA1c (model 4). Results: Data from 3328 subjects (median age 14.3 years, T1D duration 5.6 years, 52.2% male) were analysed. Time in range (TIR) and time in tight range (TITR) were inversely associated with BP‐SDS and LDL‐C, while time above range (TAR), mean glucose, glucose variability (coefficient of variation (CV)) [%] and glycemia risk index showed positive associations (all p < 0.01). In multivariable regression models 1–3, TIR, TITR, TAR and glycemia risk index remained independently associated with LDL‐C and systolic BP‐SDS ( p < 0.001), with CV also independently associated with systolic BP‐SDS ( p < 0.001). In model 4 associations with SBP‐SDS were attenuated, whereas those with LDL‐C remained significant, although with a reversal direction. Conclusions: Key CGM metrics, particularly TIR and TITR, are independently associated with LDL‐C and BP in youth with T1D, highlighting their potential clinical relevance in the assessment of cardiovascular risk profile, alongside HbA1c.

Cardiovascular disease (CVD) is a major long-term complication and the leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D), with a substantially higher prevalence compared to the general population and driven by multiple interrelated risk factors—underscoring the urgent need for accurate risk assessment. To support more tailored approaches to CVD prevention, recently, five discordant phenotypic risk profiles for CVD were identified in the general population in Europe with diverse relationship between body mass index and cardiometabolic biomarkers. Here, we show their applicability in 44,212 people with T1D. Improved glycemic control was linked to a decrease in CVD risk as people with T1D with lower glycated hemoglobin belonged to the baseline concordant cluster. This supports the contention that glycemic control in people with T1D is an integral part of lowering CVD risk.

Background: To assess changes in HbA1c and weight over time after continuous glucose monitoring (CGM) initiation in adults with type 1 diabetes (T1D). Methods: Retrospective data from 4178 adults with T1D using CGM in Western Europe were analyzed. To assess changes in weight and HbA1c over 24 months after CGM initiation, paired t-tests and group-based multi-trajectory modeling were used. Findings : After 24 months of CGM initiation, a mean weight gain of 1.8kg±5.1 (p<0.0001) and 1.0kg±4.6 (p<0.0001) with a decrease in HbA1c of -1.7±10.7 mmol/mol (-0.2%±1.0; p<0.0001) and -0.7±8.9 mmol/mol (-0.1%±0.8; p<0.0001) were seen in the diabetes registry (DPV) (n=2104) and in the FUTURE/RESCUE (BE) cohort (n=2074), respectively. Three distinct bi-variate trajectories were identified in both cohorts: some weight gain with HbA1c decrease (DPV: 7.0% of cohort, weight +3.8kg, HbA1c -2.3%; BE: 20.5% of cohort, weight +1.3kg, HbA1c -1.1%), stable weight and HbA1c (DPV: 83.2%, weight +0.59kg, HbA1c-0.01%; BE: 68.1%, weight -0.27kg, HbA1c+0.2%), and weight gain with stable HbA1c (DPV: 9.9%, weight +11.1kg, HbA1c +0.01%; BE: 11.4%, weight +8.2kg, HbA1c -0.01%). Interpretation: CGM initiation resulted in a modest weight increase and HbA1c decrease. However, 10% of individuals experienced notable weight gain despite stable HbA1c, underscoring the persistent unmet need for additional strategies to avoid weight gain and improve glucose control.

Guidelines recommend GLP-1 receptor agonists (GLP-1-RA) and SGLT2-inhibitors (SGLT2i) for individuals with type 2 diabetes (T2D) at high risk of atherosclerotic cardiovascular disease (ASCVD). In the context of precision medicine, we evaluated a personalized treatment algorithm to guide the initial decision between these therapies. Using data from the observational Diabetes Prospective Follow-up registry (Germany/Austria) we studied individuals with T2D who initiated GLP-1-RA (n=1433) or SGLT2i (n=2547) in a multicenter, real-world setting. Baseline characteristics included age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), HbA1c, diabetes duration, and history of ASCVD. Non-fatal ASCVD events (myocardial infarction, angina, revascularization, stroke, transient ischemic attack, and peripheral artery disease) were analyzed using dynamic weighted survival modeling to predict the optimal treatment for each individual. The algorithm predicted 48% of individuals to have better ASCVD outcomes with GLP-1-RA and 52% with SGLT2i. GLP-1-RA-optimal individuals had on average a higher BMI (37 vs 31 kg/m2), lower eGFR (71 vs 93 ml/min per 1.73 m2) and less history of ASCVD (9 vs 18%) compared to SGLT2i-optimal individuals. However, an internal model validation showed that the predicted optimal treatment did not statistically significantly prolong the average time to a non-fatal ASCVD event compared to the suboptimal treatment (AFT parameter: 1.13; 95% CI: 0.83-1.56; HR: 0.88; 95% CI: 0.64-1.21). The personalized treatment algorithm for GLP-1-RA and SGLT2i did not result in clear individual ASCVD benefits on either drug, a finding consistent with the clinical equipoise reflected in current T2D treatment guidelines.

Aims: To characterize youth with monogenic diabetes worldwide in the SWEET database and define trends in clinical care and outcomes. Methods: Youth with monogenic diabetes between the ages of 0 and 21 years from 44 worldwide centers in the SWEET registry divided into global regions were studied in this retrospective analysis. This included 690 youth with data at diabetes diagnosis and/or follow-up at 1 year and 214 patients with data at both time points. Demographics, comorbidities, and treatments were evaluated. Results: Globally, mean age and hemoglobin A1c (HbA1c) at diagnosis were 10.1 years (SD 4.57 years) and 6.9% (52 mmol/mol) (SD 1.7%, 18 mmol/mol), respectively. At 1-year follow-up, mean HbA1c decreased by 0.4%. Average body mass index (BMI) at diabetes diagnosis was in the normal range (World Health Organization BMI SD score 0.31). At diabetes diagnosis, 3.6% presented in diabetic ketoacidosis (DKA). Seven percent were treated with oral antidiabetes medications or glucagon-like peptide-1 receptor agonists at diabetes diagnosis, increasing to 15.3% at follow-up. Overall, treatment with insulin increased by 10% at follow-up. Conclusion: Worldwide, patients with monogenic diabetes typically present during late childhood/early adolescence with mild elevation in HbA1c, normal BMI, and lack of DKA. Regional differences in demographics and treatment modalities highlight heterogeneity in presentation and management of monogenic diabetes, impacting clinical care.

Background: Glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) improve glycemic outcomes in people with type 2 diabetes, but their generalizability to routine clinical practice remains uncertain. Aim: To evaluate the real‐world effectiveness of sustained GLP‐1 RA use on haemoglobin A1c (HbA1c) over 1 to 4.5 years, using dipeptidyl peptidase 4 inhibitors (DPP‐4is) as an active comparator. Methods: Using Danish nationwide registries (2012–2022), we emulated a target trial assessing the glycemic effectiveness of GLP‐1 RAs. The primary outcome was the probability of improvement in defined HbA1c categories within 1 year. Longitudinal Targeted Minimum Loss‐based Estimation was used to estimate the primary outcome under sustained use of GLP‐1 RA and DPP 4i, controlling for baseline and time‐varying confounding. Results: We included 16 619 GLP‐1 RA initiators and 34 196 DPP‐4i initiators, each with 2.8 HbA1c measurements per patient‐year. At 1 year, the probability of any HbA1c improvement was 82.7% (95% CI: 82.0% to 83.4%) under sustained GLP‐1 RA versus 67.1% (95% CI: 66.5% to 67.6%) under DPP‐4i, an absolute difference of 15.7% (95% CI: 14.8% to 16.5%). GLP‐1 RA treatment was also associated with a lower all‐cause mortality risk, with absolute reductions of 0.4% (95% CI: 0.1% to 0.7%) at 1 year and 1.1% (95% CI: 0.3% to 2.0%) at 3 years. Conclusion: Within the limitations of this nationwide study and the available data, sustained GLP‐1 RA therapy provided superior glycemic control and was associated with a modest mortality benefit compared with DPP‐4i therapy.

Aims: Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) is a common complication that increases the risk of cardiovascular (CV) events and kidney failure. Recent therapies, including sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) and dipeptidyl peptidase IV (DPP‐4) inhibitors, show promise in improving outcomes. However, evidence of their comparative effectiveness in reducing CV and renal outcomes is scarce. Materials and Methods: We searched electronic databases such as PubMed, Scopus, and clinical trial registries for randomized controlled trials (RCTs) published between 2014 and 2024. A network meta‐analysis (NMA) was employed to evaluate the effectiveness of antidiabetic drugs on cardiorenal outcomes. Primary outcomes were (1) major adverse CV events (MACE), (2) composite renal outcomes, (3) all‐cause mortality. Other outcomes included heart failure (HF), stroke, macroalbuminuria, and a decline in estimated glomerular filtration rate (eGFR) >40% or renal replacement therapy. Results: Twenty‐six studies with 143 296 participants with T2DM and CKD were included. SGLT2 inhibitors were highly effective in reducing the risk of renal outcomes such as composite events (P‐score: 0.94), eGFR decline >40% or renal replacement therapy (0.99) and CV outcomes such as MACE (0.93) and HF (1.00) followed by GLP‐1 RA. While GLP‐1 RA was particularly effective in reducing the risk of MI (0.87), macroalbuminuria (0.86) and stroke (0.83) compared to SGLT2 inhibitors. Both SGLT2 inhibitors and GLP‐1 receptor agonists are highly effective (0.83) in reducing all‐cause mortality. DPP‐4 inhibitors had limited benefits compared to SGLT2 inhibitors and GLP‐1 RA. Conclusion: SGLT2 inhibitors followed by GLP‐1 RA provide strong benefits for CV and kidney health in patients with T2DM and CKD. SGLT2 inhibitors demonstrate superior benefit over GLP‐1 receptor agonists for HF and renal outcomes, highlighting their preferred role in these clinical scenarios.

Aim: Hospital certifications by the German Diabetes Association (DDG) are intended to ensure high-quality diabetological care. We aimed to compare Germany-wide characteristics and outcomes of hospitalized adults with diabetes in diabetes certified vs. non-diabetes certified hospitals. Methods: We analyzed in the German Diagnosis Related Groups (DRG) statistics for 2021-2023 all inpatient cases aged ≥ 20 years with and without diabetes (all types) as a main or secondary diagnosis based on ICD-10 codes. Using Wilcoxon and Chi ² -tests, characteristics of inpatient cases with diabetes were compared between diabetes certified hospitals (n=300) and non-diabetes certified hospitals (n=1,103). Results: Of 43.4 million total inpatient cases in the period from 2021 to 2023, 8.1 million (18.5%) had a documented diabetes diagnosis (94% of the cases as secondary diagnosis). In certified hospitals, 19.0% of inpatient cases had diabetes compared to 18.3% in non-certified hospitals. Although inpatient cases with diabetes had more hospital-acquired and procedure-related complications (17.2% vs. 16.7%, p<0.001), as well as higher rates of hypoglycemia (3.2% vs. 2.1%, p<0.001) and metabolic disorder (diabetic ketoacidosis: 0,5% vs. 0,4%; acute metabolic disorder with multiple complications: 2.3% vs. 1.0%, p<0.001) in certified hospitals vs. non-certified hospitals, in-hospital mortality for all diabetes cases was similar (4.5% in both). However, among those with diabetes as the main diagnosis, in-hospital mortality was significantly lower in diabetes certified hospitals (type 1 diabetes: 0.6% vs. 1.1% and type 2 diabetes: 2.3% vs. 2.9%, both p<0.001), despite a higher complication burden. Conclusions: Hospitalized people with diabetes as the main diagnosis had lower in-hospital mortality in diabetes-certified hospitals, even though they had a higher disease burden. These findings suggest that expanded use of DDG-certified departments, including consultation services for patients whose diabetes is a secondary diagnosis, may further improve clinical outcomes.