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Introduction: Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious diseases and a higher risk of infections-related hospitalization and death. In this study, we delineated the "vaccinome" landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618,396 patients with diabetes (T1D and T2D)., Methods: Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry of the healthcare system of Lombardy Region (Italy) in 618,396 patients with diabetes and in 9,534,087 subjects without diabetes. Type of diabetes, age, mortality, and hospitalizations were retrospectively analyzed in vaccinated and unvaccinated patients., Results: Among patients with diabetes (T1D and T2D), 44.6% received the influenza vaccine, 10.9% the pneumococcal vaccine, 2.5% the anti-meningococcus vaccine and 0.7% the anti-zoster vaccine. Patients with diabetes immunized for influenza, zoster and meningococcus showed a 2-fold overall reduction in mortality risk and a decrease in hospitalizations. A 3-fold lower risk of mortality and a decrease in hospitalizations for both cardiac and pulmonary causes were also observed after influenza, zoster, and meningococcus immunization in older patients with diabetes., Conclusions: Immunization coverage is still far from the recommended targets in patients with diabetes. Despite this, influenza vaccination protected nearly 3,800 per 100,000 patients with diabetes from risk of death. The overall impressive decrease in mortality and hospitalizations observed in vaccinated patients strengthens the need for scaling up the "vaccinome" landscape in patients with diabetes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Pancreatic endocrine cells employ a sophisticated system of paracrine and autocrine signals to synchronize their activities, including glutamate, which controls hormone release and β-cell viability by acting on glutamate receptors expressed by endocrine cells. We here investigate whether alteration of the excitatory amino acid transporter 2 (EAAT2), the major glutamate clearance system in the islet, may occur in type 2 diabetes mellitus and contribute to β-cell dysfunction. Increased EAAT2 intracellular localization was evident in islets of Langerhans from T2DM subjects as compared with healthy control subjects, despite similar expression levels. Chronic treatment of islets from healthy donors with high-glucose concentrations led to the transporter internalization in vesicular compartments and reduced [H 3 ]-d-glutamate uptake (65 ± 5% inhibition), phenocopying the findings in T2DM pancreatic sections. The transporter relocalization was associated with decreased Akt phosphorylation protein levels, suggesting an involvement of the phosphoinositide 3-kinase (PI3K)/Akt pathway in the process. In line with this, PI3K inhibition by a 100-µM LY294002 treatment in human and clonal β-cells caused the transporter relocalization in intracellular compartments and significantly reduced the glutamate uptake compared to control conditions, suggesting that hyperglycemia changes the trafficking of the transporter to the plasma membrane. Upregulation of the glutamate transporter upon treatment with the antibiotic ceftriaxone rescued hyperglycemia-induced β-cells dysfunction and death. Our data underscore the significance of EAAT2 in regulating islet physiology and provide a rationale for potential therapeutic targeting of this transporter to preserve β-cell survival and function in diabetes. NEW & NOTEWORTHY The glutamate transporter SLC1A2/excitatory amino acid transporter 2 (EAAT2) is expressed on the plasma membrane of pancreatic β-cells and controls islet glutamate clearance and β-cells survival. We found that the EAAT2 membrane expression is lost in the islets of Langerhans from type 2 diabetes mellitus (T2DM) patients due to hyperglycemia-induced downregulation of the phosphoinositide 3-kinase/Akt pathway and modification of its intracellular trafficking. Pharmacological rescue of EAAT2 expression prevents β-cell dysfunction and death, suggesting EAAT2 as a new potential target of intervention in T2DM.

Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic β cells. We herein investigated the role of GLP-1R on T lymphocytes during immune response. Our data showed that a subset of T lymphocytes expresses GLP-1R, which is upregulated during alloimmune response, similarly to PD-1. When mice received islet or cardiac allotransplantation, an expansion of GLP-1R pos T cells occurred in the spleen and was found to infiltrate the graft. Additional single-cell RNA sequencing (scRNA-seq) analysis conducted on GLP-1R pos and GLP-1R neg CD3 + T cells unveiled the existence of molecular and functional dissimilarities between both subpopulations, as the GLP-1R pos are mainly composed of exhausted CD8 T cells. GLP-1R acts as a T cell-negative costimulatory molecule, and GLP-1R signaling prolongs allograft survival, mitigates alloimmune response, and reduces T lymphocyte graft infiltration. Notably, GLP-1R antagonism triggered anti-tumor immunity when tested in a preclinical mouse model of colorectal cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims of the Study: Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls., Method: Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test., Results: In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls., Conclusions: Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Autism spectrum disorders (ASDs) impair many aspects of everyday life and may prevent access to dental care, often limiting it to emergencies. Impaired oral health has long-lasting negative consequences on health status and on the acquisition of oral habits (e.g., oral respiration and grinding) or competencies (e.g., proper speech production). Children with ASD may be scared in the dental setting, which is rich in sensory stimuli and requires physical contact. Due to their behavioral manifestations, they represent a challenge for dentists and hygienists. We created a dedicated pathway with behavioral support for children with ASD to allow dental care and possibly limit the use of general anesthesia., Methods: We evaluated the effects of behavioral support in a quasi-experimental design by comparing two groups of children with ASD. The first group ( n = 84) was visited every 2 months for 3 years and received additional support (visual aids, caregiver training, and longer visit duration). A control group, matched for age and sex, was visited at least twice a year or more, if needed, according to standard healthcare guidelines., Results: Compliance with the schedule was high throughout the 3 years. The degree of collaboration significantly improved after 1 year in the supported group, while the control group did not change. At the end of the study, collaboration remained significantly higher than at the beginning in the supported group. Half of dental treatments were possible without general anesthesia in supported children. No adverse effect was apparent on collaboration due to COVID-19 restrictions., Discussion: Behavioral techniques improved the compliance of ASD children to regular dentistry visits and treatment. Furthermore, oral hygiene at home was similarly improved, addressing oral health from a lifelong perspective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Pastore, Bedin, Marzari, Bassi, Gallo and Mucignat-Caretta.)

Apoptotic pathways have always been regarded as a key-player in preserving tissue and organ homeostasis. Excessive activation or resistance to activation of cell death signaling may indeed be responsible for several mechanisms of disease, including malignancy and chronic degenerative diseases. Therefore, targeting apoptotic factors gained more and more attention in the scientific community and novel strategies emerged aimed at selectively blocking or stimulating cell death signaling. This is also the case for the TMEM219 death receptor, which is activated by a circulating ligand, the Insulin-like growth factor binding protein 3 (IGFBP3) and induces a caspase-8-dependent apoptosis of the target cells. Interestingly, stimulation of the IGFBP3/TMEM219 axis exerts an anti-proliferative effect, while blockade of the TMEM219 deleterious signal protects TMEM219-expressing cells of the endocrine pancreas, lung, and intestine from damage and death. Here, we summarize the most updated reports on the role of the IGFBP3/TMEM219 apoptotic axis in disease conditions, including intestinal disorders and diabetes, and we describe the advancements in designing and testing novel TMEM219-based targeting approaches in emerging potential clinical applications., (© 2023 The Authors. BioEssays published by Wiley Periodicals LLC.)

Diabetic kidney disease (DKD) is the first cause of end-stage kidney disease in patients with diabetes and its prevalence is increasing worldwide. It encompasses histological alterations that mainly affect the glomerular filtration unit, which include thickening of the basement membrane, mesangial cell proliferation, endothelial alteration, and podocyte injury. These morphological abnormalities further result in a persistent increase of urinary albumin-to-creatinine ratio and in a reduction of the estimated glomerular filtration rate. Several molecular and cellular mechanisms have been recognized, up to date, as major players in mediating such clinical and histological features and many more are being under investigation. This review summarizes the most recent advances in understanding cell death mechanisms, intracellular signaling pathways and molecular effectors that play a role in the onset and progression of diabetic kidney damage. Some of those molecular and cellular mechanisms have been already successfully targeted in preclinical models of DKD and, in some cases, strategies have been tested in clinical trials. Finally, this report sheds light on the relevance of novel pathways that may become therapeutic targets for future applications in DKD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: The purine nucleotide adenosine triphosphate (ATP) is released into extracellular spaces as extracellular ATP (eATP) as a consequence of cell injury or death and activates the purinergic receptors. Once released, eATP may facilitate T-lymphocyte activation and differentiation. The purpose of this review is to elucidate the role of ATP-mediated signaling in the immunological events related to type 1 diabetes (T1D)., Recent Findings: T lymphocytes mediate immune response during the onset of T1D and promote pancreatic islet or whole pancreas rejection in transplantation. Recent data suggest a potential role for eATP in early steps of T1D onset and of allograft rejection. In different preclinical experimental models and clinical trials, several drugs targeting purinergic signaling have been employed to abrogate lymphocyte activation and differentiation, thus representing an achievable treatment to prevent/revert T1D or to induce long-term islet allograft function., Summary: In preclinical and clinical settings, eATP-signaling inhibition induces immune tolerance in autoimmune disease and in allotransplantation. In this view, the purinergic system may represent a novel therapeutic target for auto- and allo-immunity., Competing Interests: Conflicts of interests P.F. is owner of patent n. 11452781. All other authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D)., Methods: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated., Results: Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001)., Discussion: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of β-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D., Competing Interests: MR has received funding for research from NovoNordisk, Sanofi, Alfasigma, Artsana, AstraZeneca, Johnson&Johnson, Medtronic, Shionogi, SOBI, Meteda and Theras. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Berra, Rossi, Mirani, Ceccarelli Ceccarelli, Romano, Sassi, Peretti, Favacchio, Pastore, Folini, Graziano, Lunati, Solerte and Fiorina.)

Insulin represents a life-saving treatment in patients with type 1 diabetes, and technological advancements have improved glucose control in an increasing number of patients. Despite this, adequate control is often still difficult to achieve and insulin remains a therapy and not a cure for the disease. β-cell replacement strategies can potentially restore pancreas endocrine function and aim to maintain normoglycemia; both pancreas and islet transplantation have greatly progressed over the last decades and, in subjects with extreme glycemic variability and diabetes complications, represent a concrete and effective treatment option. Some issues still limit the adoption of this approach on a larger scale. One is represented by the strict selection criteria for the recipient who can benefit from a transplant and maintain the lifelong immunosuppression necessary to avoid organ rejection. Second, with regard to islet transplantation, up to 40% of islets can be lost during hepatic engraftment. Recent studies showed very preliminarily but promising results to overcome these hurdles: the ability to induce β-cell maturation from stem cells may represent a solution to the organ shortage, and the creation of semi-permeable membranes that envelope or package cells in either micro- or macro- encapsulation strategies, together with engineering cells to be hypo-immunogenic, pave the way for developing strategies without immunosuppression. The aim of this review is to describe the state of the art in β-cell replacement with a focus on its efficacy and clinical benefits, on the actual limitations and still unmet needs, and on the latest findings and future directions., (© The Author(s) 2022. Published by Oxford University Press.)

Aims: Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID-19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID-19 pneumonia only accounts for a part of COVID-19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well-known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients., Materials and Methods: In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID-19 admitted to a third-level Hospital in Milan., Results: We found an increased mortality in subjects with COVID-19 and diabetes, together with an altered inflammatory profile., Conclusions: This may support the hypothesis that diabetes and COVID-19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794)., (© 2022 John Wiley & Sons Ltd.)

Aims: Abnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function in patients with type 1 diabetes., Methods: We used the SRLab-Tobii TX300 Eye tracker®, an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes., Results: Among the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes (p < 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class (p = 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy., Conclusions: Abnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy., Trial: NCT04608890., (© 2022. The Author(s).)

Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (-0.6 ± 1.8%) as well as in BMI (-1.5 ± 5.2 kg/m 2 ). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) may have important benefits for the elderly with type 2 diabetes (T2D), however some safety concerns still limit their use in patients over 70 years of age. The SOLD study (SGLT2i in Older Diabetic patients) is a multicenter study, aimed to evaluate the effectiveness and safety of SGLT2i in the older diabetic patients in a real-life setting., Materials and Methods: We analyzed a population of 739 adults (mean age 75.4 ± 3.9 years, M/F 420/319) with T2D, which started a SGLT2i-based treatment after the age of 70, with at least one year of follow-up. Data were collected at baseline, at 6 and 12 months of follow-up., Results: SGLT2i (37.5% Empagliflozin, 35.7% Dapagliflozin, 26.1% Canagliflozin, 0.7% Ertugliflozin) were an add-on therapy to Metformin in 88.6%, to basal insulin in 36.1% and to other antidiabetic drugs in 29.6% of cases. 565 subjects completed the follow up, while 174 (23.5%) discontinued treatment due to adverse events which were SGLT2i related. A statistically significant reduction of glycated hemoglobin (baseline vs 12 months: 7.8 ± 1.1 vs 7.1 ± 0.8%, p < 0.001) and body mass index values (baseline vs 12 months: 29.2 ± 4.7 vs 28.1 ± 4.5 kg/m 2 , p < 0.001) were evident during follow-up. Overall, estimated glomerular filtration rate remained stable over time, with significant reduction of urinary albumin excretion. In the subgroup of patients which were ≥ 80 years, a significant improvement in glycated hemoglobin values without renal function alterations was evident. Overall discontinuation rate during the follow-up period was different across age groups, being urinary tract infections and worsening of renal function the most common cause., Conclusion: SGLT2i are well-tolerated and safe in the elderly and appear as an effective therapeutic option, though some caution is also suggested, especially in more fragile subjects., (Copyright © 2022. Published by Elsevier Ltd.)

In the last few years, a great interest has emerged in investigating the pleiotropic effects of Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs). While GLP-1RAs ability to lower plasma glucose and to induce weight loss has allowed them to be approved for the treatment of diabetes and obesity, consistent evidences from in vitro studies and preclinical models suggested that GLP-1RAs have anti-inflammatory properties and that may modulate the immune-system. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions. This review examines some of the currently proposed molecular mechanisms of GLP-1RAs actions and explores their potential benefits in reducing inflammatory responses, which may well suggest a future therapeutic use of GLP-1RAs in new indications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Patients with type 1 diabetes (T1D) may develop severe outcomes during coronavirus disease 2019 (COVID-19), but their ability to generate an immune response against the SARS-CoV-2 mRNA vaccines remains to be established. We evaluated the safety, immunogenicity, and glycometabolic effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in patients with T1D. A total of 375 patients (326 with T1D and 49 subjects without diabetes) who received two doses of the SARS-CoV-2 mRNA vaccines (mRNA-1273, BNT162b2) between March and April 2021 at ASST Fatebenefratelli Sacco were included in this monocentric observational study. Local and systemic adverse events were reported in both groups after SARS-CoV-2 mRNA vaccination, without statistical differences between them. While both patients with T1D and subjects without diabetes exhibited a parallel increase in anti-SARS-CoV-2 spike titers after vaccination, the majority of patients with T1D (70% and 78%, respectively) did not show any increase in the SARS-CoV-2-specific cytotoxic response compared with the robust increase observed in all subjects without diabetes. A reduced secretion of the T-cell-related cytokines interleukin-2 and tumor necrosis factor-α in vaccinated patients with T1D was also observed. No glycometabolic alterations were evident in patients with T1D using continuous glucose monitoring during follow-up. Administration of the SARS-CoV-2 mRNA vaccine is associated with an impaired cellular SARS-CoV-2-specific cytotoxic immune response in patients with T1D., (© 2022 by the American Diabetes Association.)

Background: Automated insulin delivery is a game changer for type 1 diabetes treatment., Objective: To describe the benefits of automated insulin delivery in a specific complex setting., Methods: We are herein presenting a case of a patient with type 1 diabetes, in which Hybrid Closed Loop (Medtronic Minimed 670G on Auto Mode) was used over a year during automated peritoneal dialysis. The patient was previously on insulin therapy with sensor augmented pump and we switched him to Hybrid Closed Loop shortly before the begin of dialysis., Results: Automated insulin delivery produced an increase of time in range (70-180 mg/dl) from 63% to 72%, after 3 months and to 74% after one year. Moreover, no hypoglycemia/hyperglycemia urgencies occurred overall during the year., Conclusions: The case detailed here is the first report of Hybrid Closed Loop in a patient on automated peritoneal dialysis and it shows an improvement of time in range with a satisfying safety profile in a fragile, aged patient., (© 2022. The Author(s).)

Recent studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may induce metabolic distress, leading to hyperglycemia in patients affected by coronavirus disease 19 (COVID-19). We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. Although there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed toxicity on human pancreatic islets, which could be abrogated by the use of anti-interleukin-1β (IL-1β), anti-IL-6, and anti-tumor necrosis factor α, cytokines known to be highly upregulated during COVID-19. Interestingly, the receptors of those aforementioned cytokines were highly expressed on human pancreatic islets. An increase in peripheral unmethylated INS DNA, a marker of cell death, was evident in several patients with COVID-19. Pathology of the pancreas from deceased hyperglycemic patients who had COVID-19 revealed mild lymphocytic infiltration of pancreatic islets and pancreatic lymph nodes. Moreover, SARS-CoV-2-specific viral RNA, along with the presence of several immature insulin granules or proinsulin, was detected in postmortem pancreatic tissues, suggestive of β-cell-altered proinsulin processing, as well as β-cell degeneration and hyperstimulation. These data demonstrate that SARS-CoV-2 may negatively affect human pancreatic islet function and survival by creating inflammatory conditions, possibly with a direct tropism, which may in turn lead to metabolic abnormalities observed in patients with COVID-19., (© 2022 by the American Diabetes Association.)

Introduction: Predictive low-glucose suspend (PLGS) and hybrid closed-loop (HCL) systems may improve glucose control and quality of life in type 1 diabetic individuals. This is a cross-sectional, single-center study to compare the effect on metabolic control and glucose variability of PLGS and HCL systems as compared to standard sensor-augmented pump (SAP) therapy., Methods: We retrospectively analyzed 136 adults (men/women 69/67, mean age 47.3 ± 13.9 years) with T1D on insulin pump therapy, divided accordingly to type of insulin pump system ( group 1 : SAP, 24 subjects; group 2 : PLGS, 49 subjects; group 3 : HCL, 63 subjects). The groups were matched for age, gender, years of disease, years of CSII use, and CGM wear time., Results: The analysis of CGM metrics, in the three groups, showed a statistically significant different percentage of time within the target range, defined as 70-180 mg/dl, with a higher percentage in group 3 and significantly less time spent in the hypoglycemic range in groups 2 and 3. The three groups were statistically different also for the glucose management indicator and coefficient of variation percentage, which were progressively lower moving from group 1 to group 3. In the HCL group, 52.4% of subjects reached a percentage of time passed in the euglycemic range above 70%, as compared to 32.7% in those with PLGS and 20.2% in those with SAP. A positive correlation between the higher percentage of TIR and the use of auto-mode was evident in the HCL group. Finally, the three groups did not show any statistical differences regarding the quality-of-life questionnaire, but there was a significant negative correlation between CV and perceived CSII-use convenience (r = -0.207, p = 0.043)., Conclusion: HCL systems were more effective in improving glucose control and in reducing the risk of hypoglycemia in patients with type 1 diabetes, thereby mitigating risk for acute and chronic complications and positively affecting diabetes technologies' acceptance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lunati, Morpurgo, Rossi, Gandolfi, Cogliati, Bolla, Plebani, Vallone, Montefusco, Pastore, Cimino, Argenti, Volpi, Zuccotti and Fiorina.)

During the past years, solid allograft rejection has been considered the consequence of either cellular- or antibody-mediated reaction both being part of the adaptive immune response, whereas the role of innate immunity has been mostly considered less relevant. Recently, a large body of evidence suggested that the innate immune response and its soluble mediators may play a more important role during solid allograft rejection than originally thought. This review will highlight the role of novel soluble mediators that are involved in the activation of innate immunity during alloimmune response and solid allograft rejection. We will also discuss emerging strategies to alleviate the aforementioned events. Hence, novel, feasible, and safe clinical therapies are needed to prevent allograft loss in solid organ transplantation. Fully understanding the role of soluble mediators of innate immune system activation may help to mitigate solid allograft rejection and improve transplanted recipients' outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)