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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year-old children during a camp.
A total of ...30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP).
Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25(th)-75(th) percentiles): 0.0% (0.0-2.2) vs. 2.2% (0.0-12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5) vs. 59.7% (21.2) (P = 0.430), but with increased mean glucose 173 mg/dL (36) vs. 150 mg/dL (39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (13.5) vs. 63.1% (11.0) (P = 0.022) and increased mean glucose 169 mg/dL (23) vs. 147 mg/dL (23) (P < 0.001).
This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.
Highlights
In 2021 as a whole we report an increase (22% to 35%) in incidence of type 1 diabetes compared to the years 2017 to 2020.
A peak of incidence in the last 4 months of 2021, when the “fourth ...wave” of COVID‐19 peaked in Italy, has been observed.
In the last quarter of 2021 there was a significant increased type 1 diabetes incidence in the age group under 12 years.
We speculate that SARS‐CoV‐2 infection may have had an impact on type 1 diabetes incidence in children, especially in age groups not protected by vaccination.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
SARS-CoV-2 causes lesions, in addition to lung, in endocrine organs such as the pancreas through ACE2 receptor. Recently the relationship between SARS-CoV-2 exposition and the incidence or evolution ...of clinical autoimmune diabetes has attracted the attention of diabetologists.
We report the analysis of the clinical history of a child diagnosed for insulin-dependent diabetes mellitus (Type 1 diabetes) at the time a paucisymptomatic COVID-19 infection occurred, followed by well-controlled metabolic status. As opposite to previous findings SARS-CoV2 did not cause ketosis and ketoacidosis. Polydipsia was reported a few months and weight loss 4 weeks before SARS- CoV-2 infection suggesting that SARS-CoV-2 could not be the trigger of Type 1 diabetes in this patient.
SARS-CoV-2 in this patient was an unexpected event in the course of disease. We advance the hypothesis that the SARS-CoV-2 infection, even if paucisymptomatic could have acted in the present case report as a hypothetical downstream precipitating factor; whilst the inciting triggering event of the autoimmune disease, as confirmed by the presence of circulating autoantibodies, could have occurred even before, as generally assumed for this category of disorders. The precipitating mechanism could have been the acute interaction between virus and the ACE receptor on the beta cells, at the time that hyperglycemia and glycosuria were ascertained, and HbA1c levels confirmed a metabolic dysregulation over the previous 3 months in absence of ketoacidosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Acromegaly is a rare disease that results from growth hormone (GH) excess. Diabetes mellitus, hypertension,cardiomyopathy, and obstructive sleep apnoea syndrome( OSAS) are frequent complications.
...Identify a useful system to obtain a reliable remote monitoring of glucose and the most important vital parameters in the acromegalic subjects.
Sixteen acromegalic patients (from 30 to 73 years old) were enrolled. We provided health monitor devices to the patients for continuous acquisition of physiological signals including twelve-lead electrocardiography (EKG) and nocturnal SpO2. At the same time, we applied on the same patients the blinded continuous glucose monitoring system(CGMS).
The lowest saturation peaks at night (<80%) were achieved in patients with a known diagnosis of OSAS. A positive correlation was demonstrated between the lowest oxygen saturation values and the CGM peaks (pV <0,0001) and between the average values of oxygen saturation and CGM (pV<0,0003). Patients with a previous diagnosis of OSAS, obtained by polysomnography, showed on the multiparametric monitor recordings superimposable to their known condition. Instead we noticed a discordance in the two EKG recording: the wireless mode showed an irregular rhythm in 5/16 patients, which was not confirmed by the recording mode with cables.
The health monitor device associated with CGM may be a new useful and versatile tool for fragile patients who can self-manage remote monitoring, and for physicians who can obtain real-time information for the clinical and therapeutic management of patients. It is also a useful tool for the follow-up of patients with OSAS. Moreover, once the interference of the OSAS is excluded, the CGM allows us to obtain a more reliable and accurate diagnosis of DM.
Background Tight glycemic control is essential for the normal growth and development of preschool children. The aim of our study was to evaluate the impact of advanced hybrid closed loop (AHCL) ...systems in a real-life setting in children younger than 6 years. Methods We conducted a two-center prospective study. We enrolled 19 patients with a median age at disease onset of 2.6 years interquartile range (IQR) 1.6; 4.4 and a median disease duration of 1.4 years (IQR 0.9; 2.8) who were switched to AHCL from multiple daily injections or open-loop insulin therapy and with a 6-month follow-up. Clinical data, sensor glycemic metrics, and pump settings were collected and analyzed. Results After 6 months of follow-up, there was a significant reduction in median HbA1c ( p = 0.0007) and glucose management indicator ( p = 0.03). A reduction in both mild (>180 mg/dL) ( p = 0.04) and severe (>250 mg/dL) ( p = 0.01) hyperglycemia was observed after 1 month of auto mode, and in mild hyperglycemia, it persisted up to 6 months ( p = 0.02). A small increase in time below range (<70 mg/dL) was observed ( p = 0.04) without a significant difference in time <54 mg/dL ( p = 0.73). Time in range increased significantly, reaching a 10% increment ( p = 0.03) compared with baseline. A significant reduction in the average sensor glucose was observed ( p = 0.01) while coefficient of glucose variability (CV%) remained stable ( p = 0.12). No episodes of ketoacidosis or severe hypoglycemia have been recorded. Conclusion AHCL systems are effective and safe for children younger than 6 years and should be considered as a valid therapeutic option from diabetes onset.
Autoimmune endocrine disorders, such as type 1 diabetes (T1D) and thyroiditis, at present are treated with only hormone replacement therapy. This emphasizes the need to identify personalized ...effective immunotherapeutic strategies targeting T and B lymphocytes. Among the genetic variants associated with several autoimmune disorders, the C1858T polymorphism of the protein tyrosine phosphatase non-receptor type 22 (
) gene, encoding for Lyp variant R620W, affects the innate and adaptive immunity. We previously exploited a novel personalized immunotherapeutic approach based on siRNA delivered by liposomes (lipoplexes) that selectively inhibit variant allele expression. In this manuscript, we improved lipoplexes carrying siRNA for variant C1858T by functionalizing them with Fab of Rituximab antibody (Ritux
-Lipoplex) to specifically target B lymphocytes in autoimmune conditions, such as T1D. Ritux
-Lipoplexes specifically bind to B lymphocytes of the human Raji cell line and of human PBMC of healthy donors. Ritux
-Lipoplexes have impact on the function of B lymphocytes of T1D patients upon CpG stimulation showing a higher inhibitory effect on total cell proliferation and IgM+ plasma cell differentiation than the not functionalized ones. These results might open new pathways of applicability of Ritux
-Lipoplexes, such as personalized immunotherapy, to other autoimmune disorders, where B lymphocytes are the prevalent pathogenic immunocytes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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⁺CD25high 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-1low and PD-1high 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-1low and PD-1high 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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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