Type 1 diabetes (T1D) is recognized as a complex metabolic condition associated with hormonal dysregulation and early complications. This study aimed to evaluate salivary metabolic hormones and adipokines in children and young adults with T1D, and to assess their association with early markers of metabolic and vascular complications. Demographic, anthropometric, and clinical data were collected from 349 children and young adults with T1D, classified according to weight status. Salivary concentrations of metabolic hormones and adipokines were measured using a multiplex immunoassay. Compared with normal weight (NW) individuals, overweight/obese (OW) showed worse clinical outcomes, including higher HbA1c, lower eGFR, higher blood pressure, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides. No differences in salivary hormone concentrations were observed according to weight status, while several hormones were significantly associated with clinical outcomes. HbA1c results inversely associated with ghrelin and glucagon-like peptide−1 (GLP-1) (p-value = 0.009 and p-value = 0.027, respectively), and positively with plasminogen activator inhibitor-1 (PAI-1) (p-value = 0.022). Renal function showed associations with ghrelin (p-value = 0.024), leptin (p-value <0.001), and visfatin (p-value = 0.002). Blood pressure was associated with ghrelin (p-value = 0.025) and leptin (p-value = 0.039), while lipid profile parameters were associated with ghrelin (HDL-C, p-value = 0.019) and glucagon (triglycerides, p-value = 0.034). Salivary metabolic hormones and adipokines are associated with early markers of metabolic and vascular dysfunction in young individuals with T1D, independently of weight status. These findings suggest a potential role for these biomarkers in early diabetes-related complications.

CONTEXT:The developing brain is particularly vulnerable to glycemic extremes in early-onset type 1 diabetes (T1D). However, how treatment-specific modalities may influence long-term neurodevelopmental trajectories remains poorly understood. OBJECTIVE:To characterize multimodal MRI neurodevelopmental profiles in pediatric T1D and evaluate treatment-related effects of multiple daily injections (MDI) vs continuous subcutaneous insulin infusion (CSII) on brain structure, function, and test whether glycated hemoglobin (HbA1c)-linked imaging features relate to executive-working-memory performance. METHODS:Sixteen children with T1D (8 MDI and 8 CSII from diagnosis) and eight controls underwent structural MRI, diffusion MRI, and resting-state fMRI. Union Recursive Feature Elimination selected gray matter (GM), white matter (WM), and resting-state functional connectivity (rs-FC) features discriminating groups; regression related selected features to long-term age-adjusted mean HbA1c. NEPSY-II Word List Interference (WI) was administered; control-referenced WI outcomes were examined vs HbA1c and HbA1c-associated structural features, including mediation. RESULTS:Functional features outperformed structural features (balanced accuracy 0.83 vs 0.67). MDI showed reduced GM/WM integrity and disrupted fronto-temporal and subcortical connectivity vs CSII and controls. Right inferior frontal gyrus (IFG) volume correlated with HbA1c (r = 0.71, P < .05) and predicted HbA1c (β = 0.28, P = .015). Higher HbA1c related to poorer WI repetition (r = -0.60, P = .013), and right IFG volume related to poorer WI repetition (r = -0.70, P = .002). Mediation supported an indirect HbA1c effect via right IFG volume (a × b = -0.676; Sobel z = -1.765, one-tailed P = .0388), explaining ∼64% of the total association. CSII had 30% lower hyperglycemia exposure than MDI and higher WI repetition mean ranks (11.19 vs 5.81; P = .023). CONCLUSION:Pediatric T1D is associated with multimodal neuroimaging alterations influenced by insulin treatment modality. CSII may confer neuroprotective benefits by improving metabolic control and preserving functional connectivity. Right IFG volume is a candidate imaging marker linking metabolic regulation to interference-sensitive executive-working-memory vulnerability.

AIM:To evaluate the impact of anti-islet antibody (IAb) screening on the general population and first-degree relatives (FDRs)/high-risk individuals and evidence-based follow-up modalities. METHODS:We performed this review through systematic searches of PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov and International Clinical Trials Registry Platform between 15 March 2006, and 15 March 2025. We selected studies on children and adolescents screened for T1D IAbs, compared with people who were not screened or IAb+ individuals who were not followed up. PICOS framework was used in the selection process. Outcome data were extracted, and a meta-analysis of DKA risk at T1D onset was performed. Quality of evidence was assessed using the GRADE approach. This study was registered with PROSPERO, CRD42024523781. RESULTS:Sixty-six studies, 53 of moderate-to-high quality, were included. Screening was associated with lower DKA rates by 23% (95% CI 18-29%, I2 = 88.8%). The risk of stage 3 T1D progression was high in younger children with persistent and/or multiple IAb+. Screening was associated with higher indicators of parental anxiety, which decreased during follow-up. Children with IAb positivity were monitored according to age and T1D stage, using HbA1c, oral glucose tolerance testing and continuous glucose monitoring (CGM). Time above 140 mg/dL was a biomarker of progression. CONCLUSIONS:Population screening with IAbs and follow-up of IAb+ individuals helps decrease DKA and allows participation in intervention trials. This systematic review provides evidence for clinical practice on the screening timing, modalities and follow-up. Further studies on the use of CGM are expected.

Type 1 diabetes (T1D) requires lifelong insulin therapy. Although multiple daily injections (MDI) remain widely used, advanced technologies, such as continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) system have demonstrated benefits in glycemic control and quality of life (QoL). However, comparative data on these modalities in pediatric population are still limited. This study examined the associations between therapy type, clinical outcomes, and health-related QoL (HRQoL) in children and adolescents with T1D. Demographic, anthropometric, and clinical data were collected from 262 children and adolescents with T1D. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module. Among participants, 62

Diabetic peripheral neuropathy (DN) is a major complication of type 1 diabetes (T1D), frequently subclinical in youth. Although international pediatric guidelines recommend annual screening, adherence in pediatric care is uncertain. This study aimed to assess DN screening practices in Italian pediatric diabetes centers and identify barriers to implementation. Between December 2024 and May 2025, we conducted a nationwide, cross-sectional survey among Italian centers affiliated with the ISPED Diabetes Study Group. One respondent per center completed a 27-item questionnaire exploring organizational features, DN screening practices, and professional training. Forty-eight centers responded to the survey. Written internal protocols for DN screening were available in 22.9

To evaluate efficacy and safety of continuous glucose monitoring (CGM) and automated insulin delivery (AID) in infants. A retrospective multicenter study (13 centers) of 76 children diagnosed with antibody-positive type 1 diabetes before age 2. Outcomes at 12 months were compared between AID users (n = 47) and multiple daily injections (MDI)/SAP users (n = 29). AID systems included Medtronic 780 G (38%), Tandem Control-IQ (38%), and CamAPS FX (24%). CGM median wear time was 97.0% (93.3; 98.1). AID users achieved significantly higher TIR (65% vs. 56%, P = 0.041) and time in tight range (TITR) (42% vs 32.5%, P = 0.038). In multivariable regression, AID was the sole independent predictor of lower HbA1c (P = 0.035). Zero severe hypoglycemia (SH) events occurred in the AID group (vs. 7.1% in MDI/SAP). Use of CGM is safe in very young children, with AID systems proving superior to traditional therapy. This real-world evidence supports incorporating AID consideration into future international guidelines from the time of pediatric diagnosis.

To use high-fidelity simulation to validate the clinical applicability and safety of the recently updated Italian Society for Pediatric Endocrinology and Diabetes (ISPED) recommendations for the management of diabetic ketoacidosis (DKA). Expert pediatric diabetologists participated in a full-day simulation session. Teams of four managed three advanced scenarios on a pediatric manikin: severe DKA, DKA with cerebral edema, and DKA with acute kidney injury (AKI). During the scenarios, teams utilized the new guidelines as a paper protocol, a digital application, and an AI chatbot. Each session was followed by a structured debriefing to analyze decisions, protocol adherence, and user experience, with feedback collected via questionnaires and discussion. The simulation confirmed the overall robustness and clinical validity of the new guidelines. Participants appreciated the increased detail on managing complications like cerebral edema and AKI. A key learning point emerged regarding uncertainty in the initial choice of fluids (normal saline vs. Ringer’s lactate). A quantitative analysis of user experience revealed a statistically significant preference for the paper protocol, which outperformed digital versions on key usability metrics, including efficiency and dependability (p < 0.001). The AI chatbot, despite being rated as highly novel, was perceived as impractical and inefficient. High-fidelity simulation is an effective methodology for prospectively validating and refining clinical practice guidelines in a controlled environment before official release. We confirm the validity of the new ISPED recommendations while identifying key areas for targeted training and the need for the user-centered design of digital support tools.

INTRODUCTION:Evidence on the long-term durability of glycemic control beyond the first year of automated insulin delivery therapy remains limited, particularly in large multicenter pediatric cohorts. The present study aimed to evaluate long-term effectiveness and identify determinants of sustained optimal outcomes over 3 years of MiniMed™ 780G use in youth with type 1 diabetes (T1D). MATERIALS AND METHODS:In this longitudinal, multicenter, real-world study, 359 youth with T1D (median age 12.2 years, 50.9% female) from 20 Italian pediatric diabetes centers were followed for 3 years after MiniMed 780G initiation. Glucose metrics, insulin delivery parameters, device settings, and engagement indicators were analyzed at 1, 2, and 3 years. Longitudinal changes were assessed using linear mixed-effects models. Multivariable logistic regression identified predictors of achieving time in tight range target (TITR ≥ 50%) at 3 years. RESULTS:Median time in range (TIR) remained within international targets but declined modestly from 75% at 1 year to 74% at 3 years (P = 0.002). The percentage of automatic correction boluses increased over time, whereas user-initiated boluses and carbohydrate entries declined (P < 0.001). Youth with higher TIR at 1 year showed a progressive reduction in TIR and greater increase in automated corrections (time × group interaction P < 0.001). At 3 years, higher SmartGuard use (odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03-1.23; P = 0.007), optimal system settings (OR: 3.21, 95% CI: 1.33-7.77; P = 0.010), and lower automatic correction boluses (OR: 0.84, 95% CI: 0.80-0.89; P < 0.001) were independently associated with achieving TITR ≥50%. CONCLUSIONS:MiniMed 780G provides sustained glycemic control over 3 years. However, progressive reliance on automated corrections and reduced user engagement may attenuate tight glycemic control, highlighting the need for ongoing education and proactive device optimization.

Studies of individuals at risk for developing type 1 diabetes (T1D) have demonstrated that the disease is a continuum that progresses sequentially through distinct identifiable stages before the onset of symptoms. Screening for islet antibodies (IAbs) in at-risk children for T1D (first-degree relatives or those with human leukocyte antigen genetic risk) and in the general population is becoming increasingly common in some countries. The main aim of the T1D screening program is to reduce rates of diabetic ketoacidosis (DKA) at diagnosis and to participate in research protocols that receive T1D-modifying therapies to delay clinical onset. These advantages are generally balanced with the psychological symptoms (such as anxiety and depression) that this information could produce in healthy children-adolescents and their parents, and the costs of the screening. Optimal ages for performing IAb screening in the general population have been established by cohort analyses in several studies. Primary care physicians can be responsible for family enrollment and capillary blood sampling in the general population. For follow-up of individuals who screen positive for IAbs, both age and the number of IAbs detected influence how frequently and intensively monitoring is recommended, as well as whether referral to a specialist care center is advised. Measures considered for monitoring include IAbs, hemoglobin A1c, random blood glucose, oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM). This article describes how such evidence has been implemented in Italy, offering practical insights into integrating screening into routine pediatric care.

CONTEXT:Anti-transglutaminase antibodies (anti-TTG IgA) titer is associated with mucosal damage in celiac disease (CD). OBJECTIVE:The primary focus was to correlate anti-TTG IgA titer, HbA1c when CD occurs (HbA1cCD), and Marsh grade in children and adolescents with type 1 diabetes (T1D) at the time of CD diagnosis. As secondary outcomes, we assessed the optimal anti-TTG IgA upper limit of normal (ULN) cutoff for sparing biopsy, and personal and familial autoimmunity history in the individuals with T1D and CD (T1D-CD) compared with T1D-only. METHODS:In this retrospective observational study, among 6933 individuals with T1D onset (2010-2019), 556 were grouped according to CD onset: before (CD_FIRST), concomitant (CD_CONCOMITANT), or after T1D (T1D_FIRST), and compared with 141 T1D without CD. Measures included HbA1cCD, fold-anti-TTG IgA, anti-TTG IgA cutoff, and autoimmunity history of both groups, as well as Marsh grade in T1D-CD. RESULTS:In youths with T1D, HbA1cCD was associated with increased fold-anti-TTG IgA (Spearman r = 0.14, P = .0047). The optimal anti-TTG IgA cutoff for sparing biopsy was 11 ULN. Autoimmunity was prevalent in T1D-CD individuals, who showed more comorbidities than controls (χ2 25.4, P < .001), particularly the CD_FIRST (P < .001). CONCLUSION:In children with T1D-CD, worse glucometabolic control is associated with an increase in fold anti-TTG IgA and with worse Marsh grade. A slightly higher anti-TTG IgA cutoff may be necessary for sparing biopsy compared to children in the general population. Higher prevalence of autoimmune comorbidities in CD_FIRST suggests that screening for T1D in the CD population should be mandatory.

Background:Automated insulin delivery (AID) systems have demonstrated significant improvements in glycemic control in children and adults with type 1 diabetes, but long-term real-world data in preschool-aged children remain limited, particularly in Europe, where Control-IQ is not approved for children under 6 years. This study aimed to evaluate the long-term effectiveness and safety of the t:slim X2 insulin pump with Control-IQ technology in children aged 0.5-5 years compared with those aged 6-10 years in a real-world multicenter Italian cohort. Methods:In this longitudinal, observational study conducted from 2020 to 2023, data were collected from 32 Italian centers on children <11 years diagnosed with type 1 diabetes for at least six months and using the t:slim X2 with Control-IQ technology (CIQ). Participants were grouped into 0.5-5 years or 6-10 years at CIQ initiation. Primary endpoints were the percentage of time spent in range (TIR, 70-180 mg/dL) and in tight range (TITR, 70-140 mg/dL) in the two age groups, evaluated according to children's demographic, socioeconomic, and clinical characteristics using mixed-effects models for repeated measures. Findings:We evaluated 253 children with 18-month follow-up, 131 into the 0.5-5-year group and 122 in the 6-10-year group. In the 0.5-5-year group, TIR and TITR increased significantly from baseline to 6 months and were then maintained through 18 months. In the 6-10-year group, similar improvements were observed, with no statistically significant differences between age groups in the TIR or TITR trajectories. In the adjusted mixed-effects models, TIR increased from baseline to 6 months by 5.45% (95% CI 3.78-7.11) and TITR increased by 5.56% (95% CI 3.60-7.51), with stabilization thereafter. Children of parents with a high level of education had a significantly greater mean TIR. A longer interval between T1D diagnosis and CIQ initiation was associated with a lower mean TITR (-1.21%, 95% CI -2.32 to -0.10). During observation, there were no episodes of severe hypoglycemia in younger children and only one episode in a 6-10-year-old. One episode of DKA occurred after the start of CIQ in a younger child. Interpretation:CIQ was associated with sustained improvements in glycemic outcomes, especially within the first six months. Adverse events were rare. These findings support potential supervised off-label use in young children. Funding:No specific funds were received for this study.

Background:To assess the real-world effectiveness of switching from first-generation basal insulins (1BIs) to either glargine U300 (Gla-300) or degludec U100 (Deg-100) in children and adolescents with type 1 diabetes (T1D), using data from the Italian ISPED CARD clinical registry. Materials and Methods:This multicenter retrospective observational study included 1063 pediatric patients with T1D from 22 diabetes centers across Italy who switched from 1BI to either Gla-300 (64.6%) or Deg-100 (35.4%) between 2021 and 2023. Propensity score matching (PSM) was applied to create comparable groups (n = 353 per group). Primary endpoint was the change in HbA1c at 6 months. Secondary endpoints included fasting blood glucose (FBG), standardized body mass index (BMI/SDS), and insulin doses at 6 and 12 months. Longitudinal models for repeated measures were used to assess treatment effectiveness. Results:Both groups showed significant and clinically relevant reductions in HbA1c at 6 months from ~ 8.7% to ~ 7.4% (-1.3 percentage points), maintained at 12 months, with no significant differences between groups. FBG also decreased significantly in both groups, slightly favoring Deg-100, but without statistical significance between groups. BMI/SDS remained stable. Gla-300 was associated with a slight increase in basal insulin dose over 12 months, while Deg-100 showed a temporary reduction at 6 months. A significant reduction in short-acting insulin dose (-0.03 U/kg) was observed in both groups. Conclusion:Switching from 1BI to either Gla-300 or Deg-100 significantly improves glycemic control in pediatric T1D patients without weight gain. Although both insulins showed comparable effectiveness, differences in titration patterns highlight the need for individualized treatment strategies and improved clinician education in insulin optimization. Safety outcomes, particularly hypoglycemia, could not be assessed.