Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes.

OBJECTIVES: A connection between thyroid hormones (THs) and diverse metabolic pathways has been reported. We evaluated thyroid function and tissue sensitivity to THs in children and adolescents with T1D in comparison to euthyroid controls. Additionally, we investigate whether a relationship exists between sensitivity indices and metabolic parameters. METHODS: A retrospective analysis was conducted on 80 pediatric patients diagnosed with T1D. Clinical parameters, TSH, FT3, FT4, and the presence of MS were documented. Additionally, indices of peripheral sensitivity (FT3/FT4 ratio) and central sensitivity (TSH index, TSHI; TSH T4 resistance index, TT4RI; TSH T3 resistance index, TT3RI) were assessed. Thirty healthy subjects were considered as controls. RESULTS: The overall prevalence of MS was 7.27 %, with MS identified in 8 out of 80 (10 %) T1D subjects; none of the controls manifested MS (p<0.01). No significant differences were observed in indexes of tissue sensitivity to THs between subjects with or without MS (all p>0.05). Correlations between THs and indexes of THs tissue sensitivity and metabolic parameters in controls and T1D patients were noted. CONCLUSIONS: This study affirms a heightened prevalence of MS in children with T1D compared to controls and underscores the potential role of THs in maintaining metabolic equilibrium.

Safety, Metabolic and Psychological Outcomes of Medtronic MiniMed 780G™ in Children, Adolescents and Young Adults: A Systematic Review.

The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes.

Performance of Tandem Control IQ During Outdoor Physical Activity in Children and Adolescents with Type 1 Diabetes.

Background: Few data are available in children with type 1 diabetes using automated insulin delivery systems during physical activity (PA). We evaluated the time in range (TIR) during 2-h of outdoor PA in children using t:slim X2 with Control-IQ® technology. Materials and Methods: Caucasian children and adolescents, aged 9-18 years using t:slim X2 with Control-IQ technology were recruited during a local sporting event. Participants were divided into two groups: Group A practiced endurance activities for 60 min (1000-meter run, a jump circuit) and then power activities for 60 min (80-meter run, long jump); Group B practiced power activities for 60 min and then followed by endurance activities for 60 min. Ninety minutes before the PA, participants had lunch and self-administered a low-dose insulin, reduced by 50% compared to their regularly calculated meal dose per pump calculator. DexcomG6® data were downloaded. Results: Twenty-six children were recruited, 2 refused PA. Participants were divided as follows: 13 in Group A (7 males, median age 14.6 years) and 11 in Group B (8 males, median age 13.5 year). The mean glucose level when PA started was similar between groups (P = 0.06). Subjects in Group B showed a higher TIR than those in Group A ([50.4%, 95% confidence interval, CI: 33.8-75] vs. 39.6% [95% CI: 26.9-58.3], respectively [P = 0.39]). A significantly better TIR in Group B (53.8%, 95% CI: 30.2-96.1) compared to Group A (17.4%, 95% CI: 7.3-41.7, P = 0.02) was recorded during the first session. During the second session, TIR increased in both groups. There were no episodes of serious or severe hypoglycemia. Conclusions: No serious or severe hypoglycemic episodes were recorded during PA performed 90 min after lunch. Future studies using t:slim X2 with Control-IQ technology are necessary.

Early lung diffusion abnormalities and airways' inflammation in children with type 1 diabetes.

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.

New therapies towards a better glycemic control in youths with type 1 diabetes.

Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.

Corrigendum: The silent epidemic of diabetic ketoacidosis at diagnosis of type 1 diabetes in children and adolescents in italy during the covid-19 pandemic in 2020.

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Twenty years of the International Society for Pediatric and Adolescent Diabetes Science Schools programs: Assessment of their impact on the participants' personal careers and networking development.

OBJECTIVE: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success. METHODS: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities. RESULTS: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards. CONCLUSIONS: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities.

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020.

Aim/Hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019. Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019. Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively). Conclusions/Interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.

Abnormalities of the oculomotor function in type 1 diabetes and diabetic neuropathy.

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.

Immunogenicity and Safety of SARS-CoV-2 mRNA Vaccines in a Cohort of Patients With Type 1 Diabetes.

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.

Neonatal Diabetes in Patients Affected by Liang-Wang Syndrome Carrying KCNMA1 Variant p.(Gly375Arg) Suggest a Potential Role of Ca2+ and Voltage-Activated K+ Channel Activity in Human Insulin Secretion.

Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca2+ and voltage-activated K+ channel (BKC). The KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K+ current. The phenotype of this variant includes developmental delay, and visceral and connective tissue malformations. So far, only three cases of LWAS have been described, one of which also had neonatal diabetes (ND). We present the case of a newborn affected by LIWAS carrying the p.(Gly375Arg) variant who manifested diabetes in the first week of life. The description of our case strongly increases the frequency of ND in LIWAS patients and suggests a role of BK inactivation in human insulin secretion. The knowledge on the role of BKC in insulin secretion is very poor. Analyzing the possible mechanisms that could explain the association of LIWAS with ND, we speculate that BK inactivation might impair insulin secretion through the alteration of ion-dependent membrane activities and mitochondrial functions in ß-cells, as well as the impaired intra-islet vessel reactivity.

Type 1 diabetes onset in Lombardy region, Italy, during the COVID-19 pandemic: The double-wave occurrence.

BACKGROUND: The Italian Lombardy region has been the epicenter of COVID-19 since February 2020. This study analyses the epidemiology of pediatric type 1 diabetes (T1D) onset during the first two pandemic waves and three previous years. METHODS: All the 13 pediatric diabetes centers in Lombardy prospectively evaluated charts of children at T1D onset (0-17 years), during year 2020. After calculating the annual incidence, the data were compared with those of the 3 previous years, using generalized linear models, adjusted for age and sex. Monthly T1D new onsets and diabetic ketoacidosis (DKA) were investigated yearly from 2017 to 2020. Data were extracted from outpatients charts of the pediatric diabetes centers and from the database of the national institute of statistics. FINDINGS: The estimated incidence proportion of T1D was 16/100·000 in 2020, compared to 14, 11 and 12 in 2019, 2018 and 2017, respectively. When adjusting for age and gender, the incidence was significantly lower in 2018 and 2017 compared to 2020 (adjusted incidence ratio: 0.73 and 0.77 respectively, with 95% CI: 0.63 to 0.84, and 0.67 to 0.83; p = 0·002 and p = 0·01), but no difference was found between the years 2020 and 2019. A reduction trend in the percentage of T1D diagnosis during the first wave (March-April) over the total year diagnoses was observed compared to previous years (11·7% in 2020, 17·7% in 2019, 14·1% in 2018 and 14·4% 2017). No difference was observed during the second wave (October-December) (32·8% in 2020, 33·8% in 2019, 34% in 2018, 30·7% in 2017). The proportion of DKA over the total T1D diagnoses during the second wave had higher trend than the first one (41·7% vs 33·3%), while severe DKA over the total DKA appeared higher during the first wave (60% vs 37·1%). INTERPRETATION: The study suggests an increase in the incidence of pediatric T1D in Lombardy throughout the past five years. Pandemic waves may have affected the clinical presentation at onset. FUNDING: None.

"CoVidentary": An online exercise training program to reduce sedentary behaviours in children with type 1 diabetes during the COVID-19 pandemic.

AIM: We explored the physical activity (PA) level and the variation in glycaemic control in children with type 1 diabetes (T1D) before and during the lockdown. Then, we proposed an online training program supported by sport-science specialists. METHODS: Parents of children with T1D (<18 years) filled out an online survey. Anthropometric characteristics, PA, play, sport and sedentary time and the medical related outcomes were recorded. An adapted online program "Covidentary" was proposed through full-training (FT) and active breaks (AB) modality. RESULTS: 280 youth (11.8 ± 3.3 years) were included in the analysis. We reported a decline in sport (-2.1 ± 2.1 h/week) and outdoor-plays (-73.9 ± 93.6 min/day). Moreover, we found an increase in sedentary time (+144.7 ± 147.8 min/day), in mean glycaemic values (+25.4 ± 33.4 mg/dL) and insulin delivery (71.8% of patients). 37% of invited patients attended the training program, 46% took part in AB and 54% in FT. The AB was carried out for 90% of the total duration, while the FT for 31%. Both types of training were perceived as moderate intensity effort. CONCLUSION: A decline of participation in sport activities and a subsequent increase of sedentary time influence the management of T1D of children, increasing the risk of acute/long-term complications. Online exercise program may contrast the pandemic's sedentary lifestyle.

The Diabetic Lung: Insights into Pulmonary Changes in Children and Adolescents with Type 1 Diabetes.

Historically, the lung was not listed and recognized as a major target organ of diabetic injury. The first evidence of diabetic lung involvement was published fifty years ago, with a study conducted in a population of young adults affected by type 1 diabetes (T1D). In recent years, there has been mounting evidence showing that the lung is a target organ of diabetic injury since the beginning of the disease-at the pediatric age. The deeply branched vascularization of the lungs and the abundance of connective tissue, indeed, make them vulnerable to the effects of hyperglycemia, in a way similar to other organs affected by microvascular complications. In this review, we focus on pulmonary function impairment in children and adolescents affected by T1D. We also cover controversial aspects regarding available studies and future perspectives in this field.

Associations Among Taste Perception, Food Neophobia and Preferences in Type 1 Diabetes Children and Adolescents: A Cross-Sectional Study.

Type 1 diabetes (T1D) is one of the most common systemic diseases in childhood which predisposes the patient to serious short-term and long-term complications, affecting all body systems. Taste and olfactory impairments were first described a long time ago in adult patients affected by diabetes (both type 1 and type 2 diabetes). However, studies evaluating taste perception, behavioral attitudes (e.g., food neophobia), and preferences toward foods in children and adolescents affected by T1D are globally lacking. Therefore, the purpose of this study was to assess taste sensitivity, food neophobia, and preferences among children and adolescents affected by T1D and healthy controls in a cross-sectional study. T1D patients presented a significantly lower ability in general to correctly identify taste qualities, especially bitter and sour tastes. Moreover, they were characterized by fewer fungiform papillae compared to controls, as well as a lower responsiveness to the bitter compound 6-n-propylthiouracil (PROP). There were no significant differences in food neophobia scores between the two groups, but differences were observed in the mean hedonic ratings for some product categories investigated. Diabetic patients showed a greater liking for certain type of foods generally characterized by sourness and bitterness, an observation probably linked to their impaired ability to perceive taste stimuli, e.g., sourness and bitterness. These results may help to enhance the understanding of these relationships in populations with elevated diet-related health risks.

Analysis of Retinal Perfusion in Children, Adolescents, and Young Adults with Type 1 Diabetes Using Optical Coherence Tomography Angiography.

We performed a cross-sectional study to analyze the retinal vasculature in children, adolescent, and young adults with type 1 diabetes using optical coherence tomography angiography (OCTA). Patients underwent funduscopic examination for diabetic retinopathy (DR) screening during an annual visit for the screening of diabetes-related complications which included the evaluation of glycated hemoglobin (HbA1c), microalbuminuria, lipid profile, arterial pressure, and neurological assessment. In addition, OCTA of the retinal vasculature was performed. Quantitative analysis of the OCTA images evaluated the vessel density at the superficial (SCP) and deep (DCP) capillary plexus of the retina. Structural vascular alterations were evaluated qualitatively. Results were compared to those obtained in a group of healthy age-, sex-, and pubertal stage-matched controls. The effect of age, disease duration, age at the disease onset, mean HbA1c since the onset, and lipid profile on vascular density was tested. Fifty-three patients (median age 15.5, IQR 12.4-19.4 years; 57% females) with type 1 diabetes and 48 controls were enrolled. The median (IQR) HbA1c was 7.6% (60 mmol/mol) (6.9-8.1%, 52-65 mmol/mol), and the median (IQR) duration of disease was 6.0 (3.3-10.3) years. Mean vessel density measured with OCTA was lower in patients compared to controls with the temporal sector showing the highest difference both in the SCP (0.55 vs. 0.57, p < 0.001) and the DCP (0.63 vs. 0.65, p < 0.001). None of the predictors was associated with the superficial and deep vascular densities. Only 2 patients had clinically detectable DR. Microvascular structural changes were found on OCTA in both of these patients and in one without funduscopic alterations. In conclusion, patients with type 1 diabetes without clinically detectable DR had decreased capillary density compared to controls on OCTA images. These findings may provide useful information for the screening and the management of patients with type 1 diabetes. Further studies are needed to confirm our results and their clinical relevance.

Performance of the Flash Glucose Monitoring System during exercise in youth with Type 1 diabetes.

AIM: Metabolic changes during exercise may affect the accuracy of glucose sensors impacting on Type 1 diabetes (T1D) management. The present study aimed at assessing the performance of the Flash Glucose Monitoring system (isCGM) during exercise and in free-living condition in youth with T1D. METHODS: Seventeen youth (53% male), aged 13.7 ±â€¯3.8 years, with T1D for 5.4 ±â€¯3.8 years, HbA1c 7.4 ±â€¯1.0% (57 ±â€¯11 mmol/mol), were enrolled. Paired isCGM, plasma (PG) and capillary (CG) glucose values (total of 136) were collected during an interval exercise (45 min at 55% VO2max load with 20 s sprints at 80% VO2max every 10 min). Paired isCGM and CG (total of 832) were collected during free-living condition. RESULTS: During exercise, isCGM absolute relative difference (ARDs) means/medians were 12.5/9.4% versus PG and 15.4/10.8% versus CG. During rest, ARDs means/medians were 16.6/12.0%. The Consensus Error Grid analysis showed 98.4% of readings during exercise and 97.24% during rest in zones A + B. Percentage of readings meeting the ISO criteria for CG levels <5.55 mmol/L was 62.5% during exercise, 53.4% during rest; for CG levels ≥5.55 mmol/L was 64.0% during exercise, 60.4% during rest. CONCLUSIONS: isCGM demonstrated similar clinical safety and performance during exercise and in everyday life; further studies are needed to confirm its accuracy during exercise.

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes.

Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.