The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2), responsible for the coronavirus disease COVID‐19, was first identified in Wuhan, China in December 2019. Diabetes, as well as other cardiovascular comorbidities, has been recognized as a major risk factor for outcomes and mortality in adults with COVID19, particularly in the elderly with type 2 diabetes. Based on these conclusions, COVID‐19 data on adults have been generalizedto youth with diabetes. Nevertheless, experience from Pediatric Diabetes practices in China (Wuhan), Italy, Spain (Catalonia) and the US (San Francisco Bay Area) consistently report only a single severe case of COVID‐19 in a 20‐year‐old female youth with type 1 diabetes (T1D) that was hospitalized for bilateral pneumonia and was subsequently discharged without complications. In Italy, information on COVID‐19 in all children with diabetes is collected on a weekly basis andthose with positive swab test or infection‐related symptoms reported to a dedicated national registry. Of a total of 15,500 children tested,11subjects with T1D (age 8‐17y) tested positive for COVID‐19; 6/11 were asymptomatic and the rest presented with mild symptoms. In the rest of locations, youth with T1D diagnosed with COVID‐19 were based on clinical suspicion and a confirmatory PCR test(Wuhan:0; Catalonia‐HSJD:3; California‐Stanford:2) and all of them were asymptomatic or had a mild course.We suggest that COVID‐19 data from adults should not be generalizedto children, adolescents and youth with diabetes as their outcomes and prognosis seem to be similar to their non‐diabetic‐peers and consistently milder than adults with diabetes.

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4⁺CD25^high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1⁺, PD-1^low and PD-1^high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1⁺, PD-1^low and PD-1^high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface.

Type 1 diabetes mellitus is a heterogeneous disorder characterized by destruction of pancreatic β cells, culminating in absolute insulin deficiency. The goals of Type 1 diabetes care, established by the Diabetes Control and Complications Trial (DCCT), are to achieve good glycemic control, to prevent hyperglycaemia (which is associated with long-term microvascular and macrovascular complications) and to avoid recurrent episodes of hypoglycaemia (which may have adverse effects on cognitive function). However, despite continuing optimization of insulin therapy regimes, the actual hormonal substitutive administration acts only to treat the symptoms without an effect on disease pathology and etiopathogenesis. In recent decades, a great deal of interest has been focused on prevention approaches in high-risk individuals, based on the hypothesis that a therapeutic intervention, if applied at the early stage of disease, might contribute to maintaining endogenous β cell function by preserving the residual β cell reservoir from autoimmune attack. This manuscript provides an overview of the most important immunotherapeutic interventions established so far for Type 1 diabetes treatment at different stages of disease that have reached an advanced stage of assessment.

Aims: The accurate prediction of blood glucose (BG) levels is critical for managing Type-1 Diabetes (T1D) in pediatric patients, where variability due to factors like physical activity and developmental changes presents significant challenges. Methods: This work explores the application of foundational models, particularly the encoder–decoder model TimeGPT, for BG forecasting in T1D pediatric patients. Methods: The performance of TimeGPT is compared against state-of-the-art models, including ARIMAX and LSTM, and multilayer perceptron (MLP) architectures such as TiDE and TSMixer. The models were evaluated using continuous glucose monitoring (CGM) data and exogenous variables, such as insulin intake. Results: TimeGPT outperforms or achieves comparable accuracy to the state of the art and MLP models in short-term predictions (15 and 30 min), with most predictions falling within the clinically safe zones of the Clarke Error Grid. Conclusions: The findings suggest that foundational models like TimeGPT offer promising generalization capabilities for medical applications and can serve as valuable tools to enhance diabetes management in pediatric T1D patients.