OBJECTIVE Evidence for using continuous glucose monitoring (CGM) as an alternative to oral glucose tolerance tests (OGTTs) in presymptomatic type 1 diabetes is primarily cross-sectional. We used longitudinal data to compare the diagnostic performance of repeated CGM, HbA(1c), and OGTT metrics to predict progression to stage 3 type 1 diabetes. RESEARCH DESIGN AND METHODS Thirty-four multiple autoantibody-positive first-degree relatives (FDRs) (BMI SD score [SDS] <2) were followed in a multicenter study with semiannual 5-day CGM recordings, HbA(1c), and OGTT for a median of 3.5 (interquartile range [IQR] 2.0-7.5) years. Longitudinal patterns were compared based on progression status. Prediction of rapid (<3 years) and overall progression to stage 3 was assessed using receiver operating characteristic (ROC) areas under the curve (AUCs), Kaplan-Meier method, baseline Cox proportional hazards models (concordance), and extended Cox proportional hazards models with time-varying covariates in multiple record data (n = 197 OGTTs and concomitant CGM recordings), adjusted for intraindividual correlations (corrected Akaike information criterion [AICc]). RESULTS After a median of 40 (IQR 20-91) months, 17 of 34 FDRs (baseline median age 16.6 years) developed stage 3 type 1 diabetes. CGM metrics increased close to onset, paralleling changes in OGTT, both with substantial intra- and interindividual variability. Cross-sectionally, the best OGTT and CGM metrics similarly predicted rapid (ROC AUC = 0.86-0.92) and overall progression (concordance = 0.73-0.78). In longitudinal models, OGTT-derived AUC glucose (AICc = 71) outperformed the best CGM metric (AICc = 75) and HbA(1c) (AICc = 80) (all P < 0.001). HbA(1c) complemented repeated CGM metrics (AICc = 68), though OGTT-based multivariable models remained superior (AICc = 59). CONCLUSIONS In longitudinal models, repeated CGM and HbA(1c) were nearly as effective as OGTT in predicting stage 3 type 1 diabetes and may be more convenient for long-term clinical monitoring.

Disclosure: J. De Schepper: None. M. Thomas: None. E. Nauwynck: None. M. den Brinker: None. H. Dotremont: None. C. Heinrichs: None. P. Lysy: None. A.M. Rochtus: None. S. Vanderstraaten: None. K. Huysentruyt: None. D. Beckers: None. M. Becker: None. Background. The few studies on pubertal development and growth in short small for gestational age (SGA) children during growth hormone (GH) therapy have reported controversial data. The objective of this retrospective study is to assess pubertal onset, pubertal height gain, menarche (M) and testes volumes (TV) in a large cohort of short SGA children who started GH therapy before puberty.Methods. In the Belux GH registry data on pubertal development and growth were analyzed in 182 short (height SDS < -2.5 and > 1 SDS below mid-parental height) SGA (birth weight and/or length SDS for gestational age < - 2 ) children, who started GH therapy before puberty and had obtained near adult height.Results. A start of GH therapy, median (Q1;Q4) age in females (n= 82) and males (n = 100) (8.8 (6.3; 10.8 ) vs 9.0 (6.6;11.6) years; p=0.188) and height SDS (-3.01 (-3.45;-2.75) vs -2.99 (-3.4;-2.76); p=0.614 ) were similar. 16 girls and 20 boys entered in puberty during the first year of GH therapy and 13 males and 4 females after more than 7 year of therapy. Mean (SD) age at onset of puberty was 1 year earlier in girls (11.7(1.5) vs (12.7(1.21) years; p< 0.001), while pubertal treatment duration was longer in boys (3.8(0.9) vs (3.4(0.7) years ; p=0.001). Absolute mean pubertal height gain was greater in males (25.0 (6.2) vs (18.1 (5.5)cm; p<0.001), while relative height gain SDS was similar ( 0.31(0.65) vs 0.31(0.80); p=0.944). Menarche occurred at a mean age of 13.9 (1.14) years or 2.2 (0.79) years after Tanner B2 stage (missing data in 4 females). At stop of GH therapy (median age : 16.5 (15.9;17.1) years) median left and right TV of 61 adolescents with available measurements was 15 (12;20)ml and 18 (12;20)ml. 10 males had a TV below the reference limit for age. Mean TV correlated positively with height SDS (p = 0.0019) and BMI SDS ( p=0.04) at examination and pubertal absolute height gain (p < 0.001). Pubertal height gain SDS correlated (p<0.001) positively with birthweight SDS and age at start of GH therapy and onset of puberty and negatively with prepubertal height gain SDS and age and height SDS at start of puberty. Age at onset of puberty and age at menarche correlated (p<0.001) negatively with height SDS at start of therapy, but positively with age at start of therapy, while the time interval between B2 and M was negatively correlated with age at start of puberty (p=0.001). Age of pubertal onset in males and females was later (p <0.0001) than in the Belgian reference population: respectively 1.3 years and 1 year. Menarche was delayed with 0.7 years. Conclusion. In Belgian GH treated prepubertal short SGA children, onset of puberty and age of menarche were slightly delayed, while a normal chronology of menarche was observed. Older age and greater height deficit at start of GH therapy are associated with a later pubertal onset, while a lower birth weight and a younger age at start of GH therapy and a greater prepubertal height gain limit the pubertal height gain. Presentation: Sunday, July 13, 2025

CONTEXT:Real-world data add value to outcomes from randomized controlled trials on the use of hybrid closed-loop systems in the management of children and adolescents with type 1 diabetes. OBJECTIVE:This multicenter prospective observational cohort study assessed real-world changes in glycemic and person-reported outcomes 1 year after Control-IQ initiation in children and adolescents with type 1 diabetes. METHODS:Between December 2021 and December 2022, all children aged 6-18 years who started Control-IQ at 13 Belgian centers were consecutively recruited. Data were collected at start of Control-IQ and after 4, 8, and 12 months. Person-reported outcomes were evaluated through questionnaires (Diabetes Quality of Life for Youth [DQOLY], Hypoglycemia Fear Survey [HFS], HAPPI-D). Data are reported as mean ± SD or least-squares mean (95% CI). RESULTS:A total of 114 children were included, with a mean age of 12.0 ± 3.2 years and of whom 61.4% were girls. Time in range (3.9-10.0 mmol/L) increased from start (51.6% [47.6-55.5]) to 12 months (64.4% [61.2-67.5]) (P < 0.001). After 12 months, HbA1c decreased from 62 mmol/mol (60-65) (7.8% [7.6-8.1]) to 54 mmol/mol (52-57) (7.1% [6.9-7.3]) and time <3.9 mmol/L from 3.9% (3.1-4.8) to 2.7% (1.9-3.5) (all P < 0.001). Children scored better on DQOLY satisfaction (70.4 [67.8-73.0] vs 74.0 points [71.3-76.6]) and DQOLY impact (54.6 [50.9-58.3] vs 51.3 points [47.4-55.1]), and parents on HAPPI-D (22.5 [21.1-23.9] vs 19.6 points [18.2-21.0]) and HFS worry (25.0 [21.6-28.4] vs 20.3 points [17.0-23.5]) (all P < 0.001). Children missed fewer days of school (287 vs 30 days/100 person-years, P < 0.001) and parents missed fewer days of work (247 vs 47 days/100 person-years, P < 0.001). CONCLUSION:One-year use of Control-IQ was associated with improved glycemic management, more diabetes-related quality of life and fewer school/work absences.

AIMS:This study evaluated 1-year real-world changes in glycaemic management, parent-reported outcomes and safety with an automated insulin delivery (AID) system in young children with type 1 diabetes (T1D). MATERIALS AND METHODS:Children aged 2-6 years whose parents agreed to initiate the Medtronic MiniMed™ 780G were enrolled at 15 centres between October 2022 and December 2023. Data were collected quarterly over 1 year during routine follow-up. Parent-reported outcomes were assessed using questionnaires (HAPPI-D [part of the HAPPI-D Protocol; Hvidøre, Adolescent, Parent, Professional, Instrument, Diabetes] and Hypoglycaemia Fear Survey [HFS]-Parent). The primary endpoint was the evolution of time in range (TIR, 70-180 mg/dL) from start to 12 months after start. Data are reported as mean ± SD or least-squares mean (95% confidence interval). RESULTS:A total of 149 children were included (mean age 4.2 ± 1.4 years; 56.4% girls). Mean T1D duration was 22.0 ± 13.0 months and 75.2% used an insulin pump before. After 1 year, TIR increased from 56.8% (54.4-59.2) to 66.6% (64.7-68.5) and haemoglobin A1c decreased from 7.6% (7.4-7.8) to 7.2% (7.1-7.4) (all p < 0.001). Time <70 mg/dL remained stable (5.0% [4.2-5.8] at start vs. 4.6% [3.9-5.3] at 12 months, p = 0.172). Parents reported less diabetes burden on the HAPPI-D (22.9 points [21.7-24.0] at start vs. 21.7 points [20.5-22.8] at 12 months, p = 0.001), while scores on the HFS-Parent did not change significantly. There were no hospitalisations for severe hypoglycaemic events and one for diabetic ketoacidosis due to infusion set occlusion. CONCLUSIONS:One-year use of an AID system in young children with T1D was safe and associated with improved glycaemic management and reduced parental burden, with limited impact on time in hypoglycaemia and related parental fear.

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength. Transitioning from pediatric to adult care presents challenges, including accurately identifying candidates for continued GH therapy, reevaluating persistent GHD, and preventing treatment discontinuation. Assessing readiness for transition and self-management skills is crucial. This Policy and Practice Review provides a comprehensive overview of current policies, regulations, and guidelines pertinent to managing GHD transition in Belgium. We integrate perspectives from national academic and nonacademic clinical stakeholders in pediatric and adult endocrine care to provide an updated policy framework. This framework underscores the importance of sustained GH therapy during transition, particularly for individuals with persistent GHD, with the goal of optimizing practices and improving outcomes during this critical period.

Hypomagnesemia in patients with type 1 diabetes (T1D) as well as in obesity has been related to insulin resistance in adults, but not yet in pediatric patients. In this observational single-center study, we aimed to investigate the relation between the magnesium homeostasis, insulin resistance, and body composition in children with T1D and in children with obesity. Children with T1D (n = 148) and children with obesity and proven insulin resistance (n = 121) and healthy controls (n = 36) were included in this study. Serum and urine samples were collected to determine magnesium and creatinine. The total daily dose of insulin (for children with T1D), results from the oral glucose tolerance test (OGTT, for children with obesity), and biometric data were extracted from the electronic patient files. Furthermore, body composition was measured via bioimpedance spectroscopy. Serum magnesium levels were decreased in both children with obesity (0.87 ± 0.07 mmol/l) and children with T1D (0.86 ± 0.07 mmol/l) compared to healthy controls (0.91 ± 0.06; p = 0.005). A lower magnesium level was associated with more severe adiposity in children with obesity, while a worse glycemic control was associated with lower magnesium levels in children with T1D. Conclusion: Children with T1D and children with obesity have decreased serum magnesium levels. An increased fat mass is associated with lower magnesium levels in childhood obesity, indicating that the adipose tissue is an important factor in magnesium homeostasis. In contrast, glycemic control was the main determining factor for serum magnesium levels in children with T1D.

Objectives To improve adult height in pubertal girls with a poor height prediction, treatment with growth hormone (GH) can be used in combination with a gonadotropin releasing hormone agonist (GnRHa), to delay closure of the growth plates. However, there are few studies to support this practice, and they show conflicting results. The objective of this trial is to assess the safety and efficacy of this combination treatment in early pubertal girls with a short predicted height, in comparison with matched controls. Design, patients, and methods We designed an open-label, multicenter, interventional case-control study. Early pubertal girls with predicted adult height (PAH) below -2.5 SDS, were recruited in tertiary care centers in Belgium. They were treated for four years with GH and GnRHa. The girls were followed until adult height (AH) was reached. AH vs PAH, AH vs Height at start, and AH vs Target Height (TH) were evaluated, as well as safety parameters. Control data were assembled from historical patient files or from patients who preferred not to participate in the study. Results Sixteen girls with mean age ( ± SD) at start of 11.0 years (± 1.3) completed the study protocol and follow-up. Their mean height ( ± SD) increased from 131.3 ± 4.1 cm (-2.3 ± 0.7 SDS) at start of treatment to 159.8 ± 4.7 cm (-1.1 ± 0.7 SDS) at AH. In matched controls, height increased from 132.3 ± 4.2 cm (-2.4 ± 0.5 SDS) to 153.2 ± 3.4 cm (-2.1 ± 0.6 SDS) (p<0.001). AH surpassed initial PAH by 12.0 ± 2.6 cm in treated girls; and by 4.2 ± 3.6 cm in the controls (p<0.001). Most treated girls reached normal adult height (>-2SD) (87.5%) and 68.7% reached or superseded the target height (TH), which was the case in only a minority of the controls (37.5% and 6.2%, respectively) (p= 0.003 and 0.001). A serious adverse event possibly related to the treatment, was a fracture of the metatarsals. Conclusion A four-year GH/GnRHa treatment in early pubertal girls with a poor PAH seems safe and results in a clinically relevant and statistically significant increase in AH compared with matched historical controls. Clinical trial registration ClinicalTrials.gov , identifier NCT00840944.

An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF.

Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P<0.001 and P <= 0.004 for all three parameters for agreement and disagreement, respectively). The ED-DSS magnitude of insulin dose change was consistently lower than that proposed by the physicians. Conclusions: Recommendations for insulin dose adjustments made by automatization did not differ significantly from recommendations given by expert physicians regarding the direction of change. These results highlight the potential utilization of ED-DSS as a useful clinical tool to manage insulin titration and dose adjustments.

AIMS:To compare insulin dose adjustments made by physicians to those made by an artificial intelligence-based decision support system, the Advisor Pro, in people with type 1 diabetes (T1D) using an insulin pump and self-monitoring blood glucose (SMBG).METHODS:This was a multinational, non-interventional study surveying 17 physicians from 11 countries. Each physician was asked to provide insulin dose adjustments for the settings of the pump including basal rate, carbohydrate-to-insulin ratios (CRs), and correction factors (CFs) for 15 data sets of pumps and SMBG of people with T1D (mean age 18.4 ± 4.8 years; eight females; mean glycated hemoglobin 8.2% ± 1.4% [66 ± 11mmol/mol]). The recommendations were compared among the physicians and between the physicians and the Advisor Pro. The study endpoint was the percentage of comparison points for which there was an agreement on the direction of insulin dose adjustments.RESULTS:The percentage (mean ± SD) of agreement among the physicians on the direction of insulin pump dose adjustments was 51.8% ± 9.2%, 54.2% ± 6.4%, and 49.8% ± 11.6% for the basal, CR, and CF, respectively. The automated recommendations of the Advisor Pro on the direction of insulin dose adjustments were comparable )49.5% ± 6.4%, 55.3% ± 8.7%, and 47.6% ± 14.4% for the basal rate, CR, and CF, respectively( and noninferior to those provided by physicians. The mean absolute difference in magnitude of change between physicians was 17.1% ± 13.1%, 14.6% ± 8.4%, and 23.9% ± 18.6% for the basal, CR, and CF, respectively, and comparable to the Advisor Pro 11.7% ± 9.7%, 10.1% ± 4.5%, and 25.5% ± 19.5%, respectively, significant for basal and CR.CONCLUSIONS:Considerable differences in the recommendations for changes in insulin dosing were observed among physicians. Since automated recommendations by the Advisor Pro were similar to those given by physicians, it could be considered a useful tool to manage T1D.

Objective Real-time continuous glucose monitoring (RT-CGM) can improve metabolic control and quality of life (QoL), but long-term real-world data in children with type 1 diabetes (T1D) are scarce. Over a period of 24 months, we assessed the impact of RT-CGM reimbursement on glycemic control and QoL in children/adolescents with T1D treated with insulin pumps. Research design and methods We conducted a multicenter prospective observational study. Primary endpoint was the change in HbA1c. Secondary endpoints included change in time in hypoglycemia, QoL, hospitalizations for hypoglycemia and/or ketoacidosis and absenteeism (school for children, work for parents). Results Between December 2014 and February 2019, 75 children/adolescents were followed for 12 (n = 62) and 24 months (n = 50). Baseline HbA1c was 7.2 ± 0.7% (55 ± 8mmol/mol) compared to 7.1 ± 0.8% (54 ± 9mmol/mol) at 24 months (p = 1.0). Participants with a baseline HbA1c ≥ 7.5% (n = 27, mean 8.0 ± 0.3%; 64 ± 3mmol/mol) showed an improvement at 4 months (7.6 ± 0.7%; 60 ± 8mmol/mol; p = 0.009) and at 8 months (7.5 ± 0.6%; 58 ± 7mmol/mol; p = 0.006), but not anymore thereafter (endpoint 24 months: 7.7 ± 0.9%; 61 ± 10mmol/mol; p = 0.2). Time in hypoglycemia did not change over time. QoL for parents and children remained stable. Need for assistance by ambulance due to hypoglycemia reduced from 8 to zero times per 100 patient-years (p = 0.02) and work absenteeism for parents decreased from 411 to 214 days per 100 patient-years (p = 0.03), after 24 months. Conclusion RT-CGM in pump-treated children/adolescents with T1D showed a temporary improvement in HbA1c in participants with a baseline HbA1c ≥ 7.5%, without increasing time in hypoglycemia. QoL was not affected. Importantly, RT-CGM reduced the need for assistance by ambulance due to hypoglycemia and reduced work absenteeism for parents after 24 months. Clinical trial registration [ClinicalTrials.gov], identifier [NCT02601729].

Abstract Current markers of β-cell function poorly reflect glucose homeostasis after diabetes onset, mainly because of the lack of integration of parameters of insulin sensitivity and β-cell responsiveness to glucose. Recently, the widespread use of continuous glucose monitoring (CGM) helped stratify glucose control in patients with long-term diabetes in new clinically relevant glucotypes. In our DIATAG study, we investigated how CGM metrics may help to segregate patients with new-onset type 1 diabetes (T1D) entering or not in partial remission (PR). We collected data from 66 pediatric patients with T1D (10.4±4.7 yo) during the first year after diabetes onset (Δ). Clinical parameters (i.e. A1C, insulin daily dose, insulin-dose adjusted A1c [IDAA1C]) and CGM data were collected at Δ+3, +6, +9, +12 months (n=168, 57% remitters [IDAA1C <9]). A panel of 46 CGM metrics was calculated on an hourly and daily basis using iglu package (1). Using unsupervised hierarchical clustering based on daily CGM metrics and clinical parameters, we identified four clusters of glucose metrics that differed from each other (p<0.05). Cluster 1 was characterized by an increased glucose stability (coefficient of variation [CV] 32±5%) within time in target (TIT [63-140 mg/dL], 83±6%) with 9% of sensor values in 63-70 mg/dL range in the early morning period. Cluster 2 exhibited a progressive decrease of TIT (60±14%) and an increase of target above range (TAR [>180 mg/dL], 20±9%) especially during the day while target in range (TIR [70-180 mg/dL]) was nearly equivalent to Cluster 1 (80±8%). Notably, CV remained low (32±5%) with little time spent below range (TBR [<70 mg/dL], 5±2%). Cluster 3 demonstrated a net increase of CV during all the nycthemere (46±7%) concomitantly to an increase of TBR (14±7%). Interestingly, TIT and TAR remained close to values from Cluster 2 (55±11%; 23±10%). Finally, Cluster 4 demonstrated major hyperglycemias (TAR, 55±13%) with increased CV (47±9%) and decreased TBR (8±6%). Interestingly, clustering allowed clinically relevant segregation of intermediate values of IDAA1C (i.e. 7.5-10) between Cluster 2 and Cluster 3, independently of the remission status. Moreover, participants at Δ+3 months distributed across all clusters (with respectively 38% in Cluster 1, 26% in Cluster 2, 29% in Cluster 3 and 7% in Cluster 4) highlighting the usefulness of CGM in characterizing disease heterogeneity from diabetes onset. In our study, a combination of CGM metrics and clinical parameters unraveled key clinical milestones of glucose homeostasis and remission status during the first year of T1D. 1. Broll et al, 2021;16(4): e0248560. Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.

BackgroundInvolving pediatric nephrological input in the clinical diagnostic work-up of children with short stature, gave rise to the hypothesis that the presence of an underlying renal tubular disorder in children with short stature is possibly underestimated. This study focussed on the added value of calculated urinary fractional excretion (FE) in the early detection of tubular disorders in children with growth failure. MethodsThis trial was designed as an observational study analyzing the medical files of children between 5 and 16 years who had been referred for short stature to the pediatric endocrinology outpatient clinic at the University Hospital Antwerp between 25/01/2015 and 01/03/2019. Based on the laboratory results of the simultaneously taken blood and urine sample, the fractional excretions of Sodium, Chloride, Potassium, Calcium, Phosphate, and Magnesium were calculated. ResultsOf the 299 patients, 54 patients had at least one deviating fractional excretion value, requiring further investigation (control sample of blood and urine, kidney ultrasound or 24 h urine collection). Genetic screening for tubulopathies was performed in 19 patients. In 5 patients (1.7% of the total population) a tubulopathy was confirmed based on genetic analysis. ConclusionThis study explored the possibility of using fractional excretions as a screening test to obtain an earlier diagnosis of tubular disorders in children with short stature. Of the 299 patients, 5 patients were diagnosed with a genetically confirmed tubulopathy. Based on these results, we propose a flowchart for an additional work-up in all children with a deviating fractional excretion.