Study protocol of a randomized controlled clinical trial investigating the effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes.

BACKGROUND: Type 1 diabetes is a main health burden with several related comorbidities. It has been shown that endothelial function, vascular structure, and metabolic parameters are considerably disrupted in patients with type 1 diabetes. Omega-3 as an adjuvant therapy may exert profitable effects on type 1 diabetes and its complications by improving inflammation, oxidative stress, immune responses, and metabolic status. Because no randomized clinical trial has examined the effects of omega-3 consumption in children and adolescents with type 1 diabetes; the present study aims to close this gap. METHODS: This investigation is a randomized clinical trial, in which sixty adolescents with type 1 diabetes will be randomly assigned to receive either omega-3 (600 mg/day) or placebo capsules for 12 weeks. Evaluation of anthropometric parameters, flow-mediated dilation (FMD) as an endothelial function marker, carotid intima-media thickness (CIMT) as a vascular structure marker, proteinuria, biochemical factors including glycemic and lipid profile, blood urea nitrogen (BUN), creatinine, high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR), as well as blood pressure will be done at the baseline and end of the trial. Also, dietary intake and physical activity will be assessed throughout the study. Statistical analysis will be performed using the SPSS software (Version 24), and P < 0.05 will be considered statistically meaningful. DISCUSSION: It is hypothesized that omega-3 supplementation may be beneficial for the management of type 1 diabetes and its complications by reducing inflammation and oxidative stress and also modulating immune responses and glucose and lipid metabolism through various mechanisms. The present study aims to investigate any effect of omega-3 on patients with type 1 diabetes. ETHICAL ASPECTS: This trial received approval from Medical Ethics Committee of Iran University of Medical Sciences, Tehran, Iran (IR.IUMS.REC.1400.070). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20210419051010N1 . Registered on 29 April 2021.

Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.

Real-Time Continuous Glucose Monitoring in the Hospital: A Real-World Experience.

BACKGROUND: Glycemic control in the hospital setting is imperative for improving outcomes among patients with diabetes. Bedside point-of-care (POC) glucose monitoring has remained the gold standard for decades, while only providing momentary glimpses into a patient's glycemic control. Continuous glucose monitoring (CGM) has been shown to improve glycemic control in the ambulatory setting. However, a paucity of inpatient experience and data remains a barrier to US Food and Drug Administration (FDA) approval and expanded/non-research use in the hospital setting. METHOD: Amid the COVID-19 pandemic, the FDA exercised its enforcement discretion to not object to the use of CGM systems for the treatment of patients in hospital settings to support COVID-19 health care-related efforts to reduce viral exposure of health care workers. Following this announcement, Scripps Health, a large not-for-profit health care system in San Diego, California, implemented CGM as the new "standard of care" (CGM as SOC) for glucose monitoring and management in the hospital. RESULTS: The present report serves to (1) detail the implementation procedures for employing this new SOC; (2) describe the patients receiving CGM as SOC, their glycemic control, and hospital outcomes; and (3) share lessons learned over two years and nearly 900 hospital encounters involving CGM. CONCLUSIONS: Here, we conclude that CGM is feasible in the hospital setting by using a dedicated diabetes care team and the CGM technology with remote monitoring.

Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes.

BACKGROUND: Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear. METHODS: In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. RESULTS: A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.

AIMS: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. MATERIALS AND METHODS: Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. RESULTS: In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. CONCLUSIONS: Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.

Managing Diabetes in Pregnancy Before, During, and After COVID-19.

Background: Pregnant women with diabetes are identified as being more vulnerable to the severe effects of COVID-19 and advised to stringently follow social distancing measures. Here, we review the management of diabetes in pregnancy before and during the lockdown. Methods: Majority of antenatal diabetes and obstetric visits are provided remotely, with pregnant women attending hospital clinics only for essential ultrasound scans and labor and delivery. Online resources for supporting women planning pregnancy and for self-management of pregnant women with type 1 diabetes (T1D) using intermittent or continuous glucose monitoring are provided. Retinal screening procedures, intrapartum care, and the varying impact of lockdown on maternal glycemic control are considered. Alternative screening procedures for diagnosing hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) are discussed. Case histories describe the remote initiation of insulin pump therapy and automated insulin delivery in T1D pregnancy. Results: Initial feedback suggests that video consultations are well received and that the patient experiences for women requiring face-to-face visits are greatly improved. As the pandemic eases, formal evaluation of remote models of diabetes education and technology implementation, including women's views, will be important. Conclusions: Research and audit activities will resume and we will find new ways for supporting pregnant women with diabetes to choose their preferred glucose monitoring and insulin delivery.

Effectiveness of a flash glucose monitoring systems implementation program through a group and telematic educational intervention in adults with type 1 diabetes.

OBJECTIVES: Verifying the clinical effectiveness and the impact on quality-of-life parameters, fear of hypoglycaemia and satisfaction with the treatment obtained with a flash glucose monitoring (MFG) devices implantation program that includes a telematic and group educational intervention in adults with type 1 diabetes. PATIENTS AND METHODS: Prospective quasi-experimental study, carried out during the COVID-19 pandemic period with a 9-month follow-up at the Virgen Macarena University Hospital, Sevilla. RESULTS: Eighty-eight participants were included (men: 46.6%; mean age (years) 38.08, SD: 9.38); years of DM1 evolution: 18.4 (SD: 10.49); treatment with multiple doses insulin (MDI) 70.5% vs 29.5% subcutaneous insulin infusion therapy (CSII)). Baseline HbA1c was 7.74% (1.08). After the intervention, the global decrease in HbA1c was -0.45% (95% CI [-0.6, -0.25], P < 0.01), increasing to -1.08% in the group that started with HbA1c ≥ 8% (P < 0.01). A mean decrease in the Fear of Hypoglycemia 15 (FH15) test score of -6.5 points was observed (P < 0.01). In the global score of the Spanish version of Diabetes Quality Of Life (DQOL-s) test, the decrease was -8.44 points (P < 0.01). In Diabetes Treatment Satisfaction Questionnaire test (DTQ-s), global score increased in + 4 points (P < 0.01). CONCLUSIONS: The incorporation of an educational program in group and telematic format within the development of MFG devices implantation strategies is an effective option, with associated benefits in quality of life and fear of hypoglycemia in adult patients with DM1. This option can be implemented in usual clinical practice.

Weight gain in type 1 diabetes during the SARS-CoV-2 pandemic. Does lockdown affect the metabolic control of pediatric patients?

Background and aims: Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population. Methods: Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed. Results: A total of 185 patients with T1D were included in the study (96 boys), aged 2-18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m2 vs. 20.9 ± 4.1 kg/m2, p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period. Conclusions: The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.

Outpatient Randomized Crossover Comparison of Zone Model Predictive Control Automated Insulin Delivery with Weekly Data Driven Adaptation Versus Sensor-Augmented Pump: Results from the International Diabetes Closed-Loop Trial 4.

Background: Automated insulin delivery (AID) systems have proven effective in increasing time-in-range during both clinical trials and real-world use. Further improvements in outcomes for single-hormone (insulin only) AID may be limited by suboptimal insulin delivery settings. Methods: Adults (≥18 years of age) with type 1 diabetes were randomized to either sensor-augmented pump (SAP) (inclusive of predictive low-glucose suspend) or adaptive zone model predictive control AID for 13 weeks, then crossed over to the other arm. Each week, the AID insulin delivery settings were sequentially and automatically updated by an adaptation system running on the study phone. Primary outcome was sensor glucose time-in-range 70-180 mg/dL, with noninferiority in percent time below 54 mg/dL as a hierarchical outcome. Results: Thirty-five participants completed the trial (mean age 39 ± 16 years, HbA1c at enrollment 6.9% ± 1.0%). Mean time-in-range 70-180 mg/dL was 66% with SAP versus 69% with AID (mean adjusted difference +2% [95% confidence interval: -1% to +6%], P = 0.22). Median time <70 mg/dL improved from 3.0% with SAP to 1.6% with AID (-1.5% [-2.4% to -0.5%], P = 0.002). The adaptation system decreased initial basal rates by a median of 4% (-8%, 16%) and increased initial carbohydrate ratios by a median of 45% (32%, 59%) after 13 weeks. Conclusions: Automated adaptation of insulin delivery settings with AID use did not significantly improve time-in-range in this very well-controlled population. Additional study and further refinement of the adaptation system are needed, especially in populations with differing degrees of baseline glycemic control, who may show larger benefits from adaptation.

The impact of COVID-19 vaccination on glycaemic control in children and adolescents with type 1 diabetes mellitus on continuous glucose monitoring.

AIMS: To investigate the impact of SARS-COV-2 vaccination on the glycaemic control in children and adolescents with T1DM wearing continuous glucose monitoring (CGM). METHODS: Caregivers of children and adolescents with T1DM were questioned regarding SARS-CoV-2 vaccination during their regular visits at the Pediatric Diabetes Outpatient Clinic. Data regarding Time in Range (TIR) (glucose levels: 70-180 mg/dl) 7 days prior and 7 days after a vaccination dose were collected in patients wearing CGM and data regarding insulin daily doses were also obtained for the insulin pump users. RESULTS: From a total of 135 patients eligible for SARS-CoV-2 vaccination, 70 (51.9%) children (37 boys, 52.9%) were vaccinated with at least one dose. Seven patients received only one dose, whereas two children received a third booster shot. No statistically significant difference was observed in either TIR (64.19% post vs. 65.53% pre, p = 0.158) or total daily insulin dose (40.08 U/day post vs. 39.32 U/day pre, p = 0,282). Additionally, in ten patients on Hybrid Closed-Loop System the percentage of the automated insulin boluses given post-vaccination was not statistically significant different compared to the boluses given pre-vaccination (15.80% vs. 16.90%, p = 0,491). CONCLUSIONS: Vaccination against SARS-CoV-2 in children and adolescents with T1DM is safe and is not associated with immediate glucose imbalance.

Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.

There is a need for safe and effective platform vaccines to protect against coronavirus disease 2019 (COVID-19) and other infectious diseases. In this randomized, double-blinded, placebo-controlled phase 2/3 trial, we evaluate the safety and efficacy of a multi-dose Bacillus Calmette-Guérin (BCG) vaccine for the prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population is made of up of adults with type 1 diabetes. We enrolled 144 subjects and randomized 96 to BCG and 48 to placebo. There were no dropouts over the 15-month trial. A cumulative incidence of 12.5% of placebo-treated and 1% of BCG-treated participants meets criteria for confirmed COVID-19, yielding an efficacy of 92%. The BCG group also displayed fewer infectious disease symptoms and lesser severity and fewer infectious disease events per patient, including COVID-19. There were no BCG-related systemic adverse events. BCG's broad-based infection protection suggests that it may provide platform protection against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogens.

Impact of COVID-19 lockdown on glucemic control in children and adolescents with type 1 diabetes mellitus.

BACKGROUND AND AIMS: To face the rapid spread of SARS-CoV2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D). PATIENTS AND METHODS: Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl) and hyperglycemia (>180 and> 250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications and lockdown of caregivers were assessed via a survey. RESULTS: 80 patients were studied (mean age 12.61±3.32 years, mean time of evolution of the disease 5.85±3.92 years), 66.2% treated with an insulin pump, users of following glucose monitoring systems: Guardian 3 (65%), FreeStyle Libre (18.8%) and Dexcom G6 (16.2%). Time in range in the cohort increased significantly during confinement (72.1±10.5 vs 74.8±10.5%; P=0.011) with lower time in hypoglycemia both <70mg/dl (4.6±3.2 vs 3.2±2.7%; P<0.001) and <54mg/dl (1.2±1.6 vs 0.7±1.2%; P<0.001) and hyperglycemia >250mg/dl (4.6±3.9 vs 3.7±3.7%; P=0.038). CV also decreased (35.8±6.3 vs 33.1±6.1%; P<0.001). Patients treated with multiple doses of insulin and poorer baseline glycemic control experienced greatest improvement. Daily insulin requirements remained stable. Regular practice of physical exercise and caregivers' confinement did not have a significant impact. CONCLUSIONS: Glycemic control in children and adolescents with T1D improved during quarantine, particularly in those with worse baseline control.

The future of telehealth in type 1 diabetes.

PURPOSE OF REVIEW: Although telemedicine and telehealth services have been a part of type 1 diabetes (T1D) clinical care for several decades, the expansion of in-home telemedicine during the COVID-19 pandemic significantly increased interest in long-term use as part of routine care. This review highlights the current literature regarding telemedicine in T1D care as well as the benefits and barriers to use in a postpandemic world. RECENT FINDINGS: Telemedicine has increased patient contact with healthcare providers, allowing for more frequent insulin dose adjustments and improvements in glycemic outcomes. In addition to routine clinical care, T1D device training and mental healthcare have been successful through telemedicine. Significant barriers to continued telemedicine care exist, including patient access and technology knowledge, language, and loss of face-to-face interaction. Healthcare providers additionally face unpredictable reimbursement and loss of continuity across state lines, and lack of resources and training for device downloads and telemedicine software. SUMMARY: Telemedicine can be successfully used in T1D care and has the potential to significantly impact glycemic and long-term outcomes. Due to continued interest for in-person visits by people with T1D and providers, it is likely that long-term telemedicine use will include a hybrid format.

Adolescents with type 1 diabetes can achieve glycemic targets on intensive insulin therapy without excessive weight gain.

INTRODUCTION: The aim of this study was to compare glycemic control and body mass index standard deviation score (BMI-SDS) before and after implementation of intensive insulin therapy using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII) in adolescents with type 1 diabetes (T1D) attending a large multidisciplinary paediatric diabetes clinic in Australia. METHODS: Prospective data were collected for cross-sectional comparison of youth aged 10.0-17.9 years (n = 669) from routine follow-up visits to the diabetes clinic in 2004, 2010, and 2016. Outcome measures included HbA1c; BMI-SDS; and insulin regimen. RESULTS: BMI-SDS remained stable between 2004 to 2016 in the 10-13 and 14-17 year age group (0.7 vs. 0.5, p = .12 and 0.7 vs. 0.7, p = .93, respectively). BMI-SDS was not different across HbA1c groups; <53 mmol/mol (7.0%), 53 to <75 mmol/mol (<7.0 to <9.0%) and >75 mmol/mol (>9.0%) in 2004 (p = .873), 2010 (p = .10) or 2016 (p = .630). Mean HbA1c decreased from 2004 to 2016 in the 10-13 year (69 mmol/mol (8.4%) vs. 57 mmol/mol (7.4%), p = <.001) and 14-17 year group (72 mmol/mol (8.7%) vs. 63 mmol/mol (7.9%), p = <.001). Prior to the implementation of MDI and CSII in 2004 only 10% of 10-13 year olds and 8% of 14-17 year olds achieved the international target for glycemic control (HbA1c 53 mmol/mol [<7.0%]). In 2016, this increased to 31% of 10-13 year olds and 21% of 14-17 year olds. CONCLUSIONS: BMI-SDS did not increase with the change to intensive insulin therapy despite a doubling in the number of adolescents achieving the recommended glycemic target of <7.0% (53 mmol/mol). HbA1c was not associated with weight gain.

Influence of the SARS-CoV-2 pandemic on paediatric patients with type 1 diabetes mellitus after one year of follow-up.

OBJECTIVES: Lockdown during the SARS-CoV-2 pandemic generated uncertainty regarding its effects on the control of type 1 diabetes (DM1). Our study aims to evaluate the influence of the pandemic on the control of paediatric patients with DM1. METHODS: Longitudinal, retrospective, observational study in patients with DM1 attended between 15/10/2019 and 15/03/2020. Data were collected at that visit and at the three subsequent visits. The second was remote in 50% of cases. The variables analysed were: type of insulin therapy, time in range (TIR), time in hypoglycaemia (THypo), time in hyperglycaemia (THyper), coefficient of variation (CV), glycosylated haemoglobin, insulin requirements and anthropometric data. RESULTS: 157 patients were recruited. At the post-lockdown visit, the TIR increased and the THyper decreased with respect to the first (p<0.00) and second (p<0.00) visits. Patients treated with subcutaneous infusion showed a higher TIR at the third visit (p=0.03) and lower insulin requirements at the fourth visit (p=0.03) compared to patients treated with multiple doses. Patients with a remote visit presented a higher TIR (p<0.00), a lower THyper (p=0.00) and lower insulin requirements (p=0.01) at the next visit. Patients aged less than 6 years presented a lower glycosylated haemoglobin (p=0.01) and insulin requirements at the third (p=0.03) and fourth (p=0.01) visits, and a lower increase in body mass index (p=0.03) over the year. CONCLUSIONS: Metabolic control improved at the post-lockdown visit. Patients treated with subcutaneous infusion, those who had a remote visit during strict lockdown and those aged less than 6 years had a better evolution.

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes.

BACKGROUND: The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. METHODS: In this context, we have developed a Master Protocol, based on the "backbone" of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. DISCUSSION: The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.

Closed-Loop Insulin Therapy in Older Adults with Type 1 Diabetes: Real-World Data.

Objective: To assess the impact of initiation of closed-loop control (CLC) on glycemic metrics in older adults with type 1 diabetes (T1D) in the real world. Methods: Retrospective analysis of electronic health records from a single tertiary diabetes center of older adults prescribed CLC between January and December 2020. Results: Forty-eight patients (mean age 70 ± 4 years, T1D duration 42 ± 14 years) were prescribed CLC and 39/48 started on the CLC. Among the CLC starters, 97.5% and 95% were prior pump and continuous glucose monitoring (CGM) users, respectively. CGM metrics showed an increase in time-in-range (62% ± 13% to 76% ± 9%; P < 0.001), a reduction in both time spent <70 mg/dL [2% (1%-3%) to 1% (1%-2%); P = 0.03] and >180 mg/dL (30% ± 11% to 20% ± 9%; P < 0.001) at 3 months. Conclusion: In this real-world data most of the older patients with T1D initiating CLC were prior pump and CGM users. Initiation of CLC improved glycemic control and reduced time spent in hypoglycemia compared with prior therapy.