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Background: Diabetes ranks among the most common chronic conditions in childhood and adolescence. It is unique among chronic conditions, in that clinical outcomes are intimately tied to how the child or adolescent living with diabetes and their parents or carers react to and implement good clinical practice guidance. It is widely recognized that the individual's perspective about the impact of trying to manage the disease together with the burden of self-management should be addressed to achieve optimal health outcomes. Standardized, rigorous assessment of behavioural and mental health outcomes is crucial to aid understanding of person-reported outcomes alongside, and in interaction with, physical health outcomes. Whilst tempting to conceptualize person-reported outcomes as a focus on perceived quality of life, the reality is that health-related quality of life is multi-dimensional and covers indicators of physical or functional health status, psychological well-being and social well- being., Methods: In this context, this Consensus Statement has been developed by a collection of experts in diabetes to summarize the central themes and lessons derived in the assessment and use of person-reported outcome measures in relation to children and adolescents and their parents/carers, helping to provide a platform for future standardization of these measures for research studies and routine clinical use., Results: This consensus statement provides an exploration of person-reported outcomes and how to routinely assess and incorporate into clincial research., (© 2024 Diabetes UK.)

Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provides additional health benefits but can cause glucose fluctuations, which challenges current AID systems. While an increasing number of clinical trials and reviews are being published on different AID systems and PA, it seems prudent at this time to collate this information and develop a position statement on the topic. This joint European Association for the Study of Diabetes (EASD)/International Society for Pediatric and Adolescent Diabetes (ISPAD) position statement reviews current evidence on AID systems and provides detailed clinical practice points for managing PA in children, adolescents and adults with type 1 diabetes using AID technology. It discusses each commercially available AID system individually and provides guidance on its use in PA. Additionally, it addresses different glucose responses to PA and provides stratified therapy options to maintain glucose levels within the target ranges for these age groups., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Appropriate glycemic control is paramount for people with type 1 diabetes (PwT1D) by the effective delivery of exogenous insulin. However, glycemic variability and the risk of severe hypoglycemia must be reliably controlled., Methods: COMET-T is a prospective, multicenter, observational study conducted in Germany, Austria, and Switzerland during 2021-2022 to assess the effectiveness and safety of insulin glargine 300 U/ml (Gla-300) after switching from other basal insulins. Out of 135 PwT1D, data of 94 patients were analyzed. The primary endpoint was the change in time in range (TIR) approximately 12 and 24 weeks after switching to Gla-300. Secondary endpoints were: change in HbA 1c , fasting plasma glucose (FPG), coefficient of variation (CV%) of plasma glucose, body weight (BW) and insulin dose., Results: Patients had mean age of 48.6 ± 16.5 years, included 39.4% males and had 18.2 ± 15.5 years T1D duration. From baseline (54.3%), TIR changed at week 12 (mean change 0.3% [± 14.3]; p = 0.8383) and at week 24 (+ 4.5% [± 14.9], p = 0.078). At week 24, TIR significantly increased in patients with body mass index > 30 kg/m 2 (8.4% [± 12.8] p = 0.0057) and patients who previously received insulin detemir (10.5%; [± 12.93]; p = 0.0005). At week 24, there was a significant reduction in the HbA 1c value (8.1 ± 0.6% vs. 7.7 ± 0.9%; p < 0.001), a reduction in the CV% of plasma glucose (36.1 ± 12.4% vs. 32.8 ± 9.6%, p = 0.056), and increase in bolus insulin dose (26.5 ± 16.3 vs. 27.9 ± 16.6 U/day; p = 0.042). FPG, BW, and basal insulin doses were not significantly changed., Conclusions: Although switching to Gla-300 in poorly controlled PwT1D did not significantly reduce TIR, it significantly decreased HbA 1c values and glycemic variability without changes in BW and basal insulin dose., Competing Interests: Declarations. Conflict of Interest: Thomas Danne has received speaker fees and research support from or has consulted for Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, Provention Bio, Roche, Sanofi, and Vertex and is a shareholder of DreaMed Ltd. Stefan Gölz has received speaker fees and research support from or has consulted for Abbott, Ascencia, Novo Nordisk, Novartis, Sanofi, Astra Zeneca, MSD, Berlin Chemia, Lilly, Boehringer Ingelheim, Johnson & Johnson, Medical Tribune, Dexcom, Roche, Menarini, Santis, EvivaMed. Julia Mader has received research support from A. Menarini Diagnostics, Novo Nordisk, Sanofi; Advisory Board: Abbott Diabetes Care, Becton–Dickinson/Embecta, Eli Lilly, Medtronic, Novo Nordisk, PharmaSens, Roche Diabetes Care, Sanofi, Viatris; speaker fees from Abbott Diabetes Care, A. Menarini Diagnostics, Becton Dickinson/Embecta, Boehringer-Ingelheim, Eli Lilly, MedTrust, Novo Nordisk, Roche Diabetes Care, Sanofi, Servier, Ypsomed; Shareholder of decide Clinical Software GmbH. Stefan Bilz has received speaker’s fees from or consulted for Amgen, Sanofi, Novartis, Bayer, Daiichi-Sankyo, Novo Nordisk; travel support from Novo Nordisk. Julia Kenzler is an employee of Sanofi-Aventis Deutschland GmbH. Ethical Approval: The study was conducted in accordance with the Helsinki Declaration of 1964. The study received approval from the institutional review board or ethics committee at each participating center. Approval reference numbers were BASEC-Nr. 2020-01997, F-2020-106, 32-605 ex 19/2. A formal written informed consent was obtained from all patients prior to their enrolment in the study. Permissions were obtained to use the DTSQ questionnaire in this study., (© 2024. The Author(s).)

Introduction: Type 1 diabetes mellitus (T1DM) is a disorder that arises following the selective autoimmune destruction of the insulin-producing beta cells. Beta-cell protective or beta-cell regenerative approaches have gained wider attention, and pharmacological approaches to protect the patient's own insulin-producing beta-cell mass have been proposed. Verapamil is an L-type calcium channel blocker that has been reported to effectively lowers beta-cell thioredoxin-interacting protein expression in rodent beta cells and islets, as well as in human islets, and thus promotes functional beta-cell mass., Methods and Analysis: The trial is a multicentre, randomised, double-blind, placebo-controlled trial in participants with T1DM, investigating the effect of verapamil on preservation of beta-cell function (Ver-A-T1D). A total of 120 participants will be randomised in a 2:1 ratio between 360 mg verapamil and placebo, administered orally once daily. T1DM patients aged ≥18 and <45 years will be eligible for recruitment within 6 weeks of diagnosis (defined as day of starting insulin therapy). The primary objective will be to determine the changes in stimulated C-peptide response during the first 2 hours of a mixed meal tolerance test at baseline and after 12 months for 360 mg verapamil administered orally once daily versus placebo. Secondary objectives include the effects of 360 mg verapamil on (1) fasting C-peptide, (2) dried blood spot C-peptide, (3) glycated haemoglobin, (4) daily total insulin dose, (5) time in range by intermittent continuous glucose monitoring measures, (6) other biomarkers related to immunological changes and beta-cell death and (6) safety (vital signs, ECG)., Ethics and Dissemination: Ethics approval was sought from the research ethics committee of all participating countries. All participants provided written informed consent before joining the study. Ver-A-T1D received first regulatory and ethical approvals in Austria. The publication policy is set in the innovative approach towards understanding and arresting type 1 diabetes grant agreement (www.innodia.eu)., Trial Registration Number: EudraCT, 2020-000435-45; ClinicalTrials.gov, NCT04545151., Protocol Version: Version 8.0 (08 November 2021)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb + ) children and adults who are at risk of (confirmed single IAb + ) or living with (multiple IAb + ) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb + ; (2) when people who are IAb + are initially identified there is a need for confirmation using a second sample; (3) single IAb + individuals are at lower risk of progression than multiple IAb + individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care., (© 2024. American Diabetes Association and European Association for the Study of Diabetes.)

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data., (© 2024 Diabetes UK.)

Background: Recent advances in insulin research open new avenues for treatment, both, for type 1 and type 2 diabetes. In developed countries, standardized "ultra-rapid-acting insulins" are now also used in addition to rapid-acting insulins. First- and second-generation basal analogs are available. Third-generation basal analogs, which only need to be applied once a week, are in the pipeline., Summary: Second-generation "ultra-rapid-acting insulins" insulins with faster onset and offset of action may be particularly useful for multiple daily injections and automated insulin delivery systems. An improved time-action profile of bolus insulin would be able to cover the rapid increase in glucose after meals with a rapid fall thereafter to avoid postprandial hypoglycemia. The third-generation basal insulins allowing once-weekly dosing made major steps toward becoming a clinical reality. However, issues with insulin affordability and availability remain problematic even in more affluent countries. Biosimilar insulins products can provide people with additional safe, high-quality, and potentially cost-effective options for treating diabetes. Particularly in low-middle income countries insulin therapy is facing issues not only of access but also storage, lack of diabetes education, and stigma., Key Message: With the new bolus insulins, the physiological insulin secretion pattern can be mimicked better and better and hypoglycemia can be avoided. With the ever longer pharmacokinetic action profiles of the basal analogs, the injection frequency is reduced, which leads to better adherence and quality of life, but these insulins are not available for everyone who needs it worldwide., (© 2024 S. Karger AG, Basel.)

Aims/hypothesis: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis., Methods: Data were collected from the large INNODIA cohort of individuals (aged 1.0-45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA 1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10-17 years; and ≥18 years., Results: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0-382.0) pmol/l (AUC 749.3 [466.2-1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA 1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001)., Conclusions/interpretation: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline., (© 2024. The Author(s).)

Competing Interests: TK held lectures for Lilly on the topic of severe hypoglycaemia.

Currently, a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first FDA-approved disease-modifying treatment of preclinical stage 2 diabetes. Research of drugs like golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40 ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes, albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies., (© 2024 S. Karger AG, Basel.)

Aim: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022., Materials and Methods: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed., Results: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively., Conclusion: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018., Methods: Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021., Results: The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33)., Conclusions: e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network. Significance statement Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data., Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation., Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals., Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Aim: This study compared the pharmacokinetics, glucodynamics and tolerability following single subcutaneous doses of ultra rapid lispro (URLi) versus Humalog in children (6-11 years), adolescents (12-17 years) and adults (18-64 years) with type 1 diabetes mellitus (T1D)., Materials and Methods: The study was a randomized, two-period, subject- and investigator-blind, crossover design in participants with T1D. Participants received a 0.2 U/kg bolus dose immediately before a liquid mixed meal tolerance test. Insulin lispro and glucose concentrations were measured., Results: The study included 13 children, 14 adolescents and 15 adults. Consistently across the age groups, onset of appearance was 4-5 min faster, the early 50% t max was reduced by 7-13 min, and exposure in the first 15 min was increased by 3.5-6.5-fold following URLi compared with Humalog (all p < .01). Exposure after 3 h was decreased by 37-58% (p = .02) and the duration was reduced by 56 min (p = .006) in children and 36 min (p = .022) in adolescents with URLi compared with Humalog. The maximum and overall exposure were similar between treatments. Postprandial glucose at 1 h was reduced by 42 mg/dl in children (p = .008), 19 mg/dl (p = .195) in adolescents and 34 mg/dl (p = .018) in adults following URLi versus Humalog. The glucose excursion during a 5-h test meal period was reduced by 16% in children and 9% in adolescents compared with Humalog. URLi was well tolerated in all age groups., Conclusions: URLi showed an accelerated insulin lispro absorption and greater postprandial glucose reduction compared with Humalog in children, adolescents and adults with T1D., (© 2023 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: This study aimed to evaluate the impact of the COVID-19 pandemic on the nutritional patterns, eating behavior, dietary content, and health-related quality of life (HrQoL) of adolescents with preexisting obesity., Methods: Anthropometric and metabolic parameters were measured, and validated questionnaires on eating habits, nutritional content, and HrQoL were administered to 264 adolescents with obesity during the COVID-19 pandemic (June 2020-June 2022) and 265 adolescents with obesity before the pandemic (from June 2017 to June 2019)., Results: Both study cohorts were comparable in age and sex distribution. Significant differences were found between the COVID-19 and pre-COVID-19 cohorts in HOMA-index (3.8 (interquartile range [IQR])): 3.3; 4.1) vs. 3.2 (IQR: 2.8; 3.5, p < 0.001), total cholesterol (208.8 mg/dL (IQR: 189.9; 214.5) vs. 198.5 mg/dL (IQR: 189.5; 207.4), p < 0.001), and GPT (93.4 (IQR 88.7; 96.5) vs. 72.8 U/L (IQR 68.9; 75.7), p < 0.001). The COVID-19 cohort reported significantly higher consumption of obesity-promoting food components, such as soft drinks, meat, sausages, fast food and delivery food, chocolate, and sweets. There was also a significant decrease in cognitive hunger control ( p = 0.002) and an increase in distractibility potential ( p = 0.001) while eating. HrQoL was significantly lower in the COVID-19 cohort ( p = 0.001)., Conclusions: This study reveals the adverse associations of exposure to the public health measures during the COVID-19 pandemic with nutrition, dietary content, and HrQoL in adolescents with preexisting obesity. These findings underscore the importance of tailored preventive and treatment strategies for addressing the specific challenges of disruptive events such as pandemics, especially in population-based context.

As the most visible and vulnerable organ of the human organism, the skin can provide an impression of its state of health. Rare forms of diabetes and endocrinopathies are often diagnosed late or primarily misinterpreted due to their rarity. Skin peculiarities associated with these rare diseases may be indicative of the underlying endocrinopathy or form of diabetes. At the same time, rare skin changes in diabetes or endocrinopathies can also be a major challenge for dermatologists, diabetologists and endocrinologists in optimal patient and therapy management. Active collaboration between these different specialist groups can therefore lead to increased patient safety, better therapeutic success and more targeted diagnostics.

Objectives: To suggest how continuous glucose monitoring (CGM) may be used intermittently in individuals with type 2 diabetes (T2D)., Materials and Methods: The use of CGM is largely in those with type 1 diabetes (T1D), in whom it makes sense to use CGM continuously as CGM provides a valuable tool to not only adjust their insulin doses but also to match it with their diet, physical activity, and other lifestyle modifications. In the case of T2D, however, especially for those not on insulin, the use of CGM may not be needed on a continuous basis. The use of CGM on an intermittent basis is rarely discussed in the literature. This article tries to provide clinical situations where CGM can be used intermittently., Results: Intermittent use of CGM defined as the "use of CGM once in 2 or 3 months or a fixed frequency," and may be useful in several situations in those with T2D. We suggest the following indications for the intermittent use of CGM in T2D-newly diagnosed patients where treatment is being started, uncontrolled diabetes where treatment is being altered, starting intensive lifestyle modification, during infections, during preoperative control, in children and adolescents with T2D, as a motivational tool to improve behavioral modification, after metabolic surgery, and in patients on steroids, apart from other indications., Conclusion: Intermittent use of CGM in T2D can be useful in special situations and can also be cost saving particularly in resource-constrained regions of the world., (© Journal of the Association of Physicians of India 2011.)

Background: The FIDELIO-DKD and FIGARO-DKD randomized clinical trials (RCTs) showed finerenone, a novel non-steroidal mineralocorticoid receptor antagonist (MRA), reduced the risk of renal and cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Using RCT inclusion and exclusion criteria, we analyzed the RCT coverage for patients with T2DM and CKD in routine clinical practice in Germany., Methods: German patients from the DPV/DIVE registries who were ≥ 18 years, had T2DM and CKD (an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m 2 OR eGFR ≥ 60 mL/min/1.73m 2 and albuminuria [≥ 30 mg/g]) were included. RCT inclusion and exclusion criteria were then applied, and the characteristics of the two populations compared., Results: Overall, 65,168 patients with T2DM and CKD were identified from DPV/DIVE. Key findings were (1) Registry patients with CKD were older, less often male, and had a lower eGFR, but more were normoalbuminuric vs the RCTs. Cardiovascular disease burden was higher in the RCTs; diabetic neuropathy, lipid metabolism disorders, and peripheral arterial disease were more frequent in the registry. CKD-specific drugs (e.g., angiotensin-converting enzyme inhibitors [ACEi] and angiotensin receptor blocker [ARBs]) were used less often in clinical practice; (2) Due to the RCT's albuminuric G1/2 to G4 CKD focus, they did not cover 28,147 (43.2%) normoalbuminuric registry patients, 4,519 (6.9%) albuminuric patients with eGFR < 25, and 6,565 (10.1%) patients with microalbuminuria but normal GFR (≥ 90 ml/min); 3) As RCTs required baseline ACEi or ARB treatment, the number of comparable registry patients was reduced to 28,359. Of these, only 12,322 (43.5%) registry patients fulfilled all trial inclusion and exclusion criteria. Registry patients that would have been eligible for the RCTs were more often male, had higher eGFR values, higher rates of albuminuria, more received metformin, and more SGLT-2 inhibitors than patients that would not be eligible., Conclusions: Certain patient subgroups, especially non-albuminuric CKD-patients, were not included in the RCTs. Although recommended by guidelines, there was an undertreatment of CKD-patients with renin-angiotensin system (RAS) blockers. Further research into patients with normoalbuminuric CKD and a wider prescription of RAS blocking agents for CKD patients in clinical practice appears warranted., (© 2023. The Author(s).)

Aims: To perform an integrated analysis of the safety and efficacy of dasiglucagon, a glucagon analogue available in a ready-to-use aqueous formulation, to treat severe hypoglycaemia (SH) in type 1 diabetes (T1D)., Materials and Methods: An integrated analysis of dasiglucagon safety was conducted on data from two placebo-controlled trials (placebo-controlled pool) and two placebo-controlled and four non-placebo-controlled trials (broad pool) in adults with T1D. An integrated analysis of dasiglucagon efficacy was conducted of pooled data and within demographic subgroups from the two placebo-controlled and two non-placebo-controlled trials in adults with T1D., Results: Dasiglucagon had a similar safety and tolerability profile to that of reconstituted glucagon. In the placebo-controlled datasets, no serious adverse events (AEs), AEs leading to withdrawal from the trial, or deaths were reported. The most common causally related AEs were nausea (56.5%) and vomiting (24.6%). The broad pool safety analysis showed similar results. Dasiglucagon efficacy in time to plasma glucose recovery from insulin-induced SH was similar to that of reconstituted glucagon (median 10.0 and 12.0 minutes, respectively) and superior to placebo (median 40.0 minutes; P < 0.0001). The median recovery time was consistent across all placebo-controlled trial subgroups., Conclusions: Dasiglucagon was well tolerated and effective as a rapid rescue agent for insulin-induced SH in people with T1D., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Competing Interests: We declare no competing interests.

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Aim: To validate a recently proposed risk prediction model for chronic kidney disease (CKD) in type 2 diabetes (T2D)., Materials and Methods: Subjects from the German/Austrian Diabetes Prospective Follow-up (DPV) registry with T2D, normoalbuminuria, an estimated glomerular filtration rate of 60 ml/min/1.73m 2 or higher and aged 39-75 years were included. Prognostic factors included age, body mass index (BMI), smoking status and HbA1c. Subjects were categorized into low, moderate, high and very high-risk groups. Outcome was CKD occurrence., Results: Subjects (n = 10 922) had a mean age of 61 years, diabetes duration of 6 years, BMI of 31.7 kg/m 2 , HbA1c of 6.9% (52 mmol/mol); 9.1% had diabetic retinopathy and 16.3% were smokers. After the follow-up (~59 months), 37.4% subjects developed CKD. The area under the curve (AUC; unadjusted base model) was 0.58 (95% CI 0.57-0.59). After adjustment for diabetes and follow-up duration, the AUC was 0.69 (95% CI 0.68-0.70), indicating improved discrimination. After follow-up, 15.0%, 20.1%, 27.7% and 40.2% patients in the low, moderate, high and very high-risk groups, respectively, had developed CKD. Increasing risk score correlated with increasing cumulative risk of incident CKD over a median of 4.5 years of follow-up (P < .0001)., Conclusions: The predictive model achieved moderate discrimination but good calibration in a German/Austrian T2D population, suggesting that the model may be relevant for determining CKD risk., (© 2022 John Wiley & Sons Ltd.)

Background: The incidence of type 2 diabetes in young people is increasing, but treatments remain limited. We aimed to assess the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycaemic control in young people with type 2 diabetes., Methods: In this double-blind, placebo-controlled trial done in 108 centres in 15 countries, participants with type 2 diabetes (aged 10-17 years; HbA 1c 6·5-10·5% [48-91 mmol/mol]) who had been previously treated with metformin or insulin were randomly assigned (1:1:1) to oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo. Participants in the empagliflozin group who did not have HbA 1c below 7·0% (<53 mmol/mol) by week 12 underwent a second double-blinded randomisation (1:1) at week 14, either remaining on 10 mg or increasing to 25 mg. Participants in the placebo group were randomly reassigned (1:1:1) in a double-blinded manner at week 26 to linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg). Investigators were masked throughout the trial and received assignments of blinded medication kits through interactive response technology for all participants at the initial randomisation and for the re-randomisations at weeks 14 and 26. The primary outcome was change from baseline in HbA 1c at 26 weeks. For empagliflozin, results were based on a pooled analysis for all participants on empagliflozin. Safety was assessed until week 52. This trial is registered with ClinicalTrials.gov, NCT03429543., Findings: Between April 26, 2018, and May 26, 2022, of 262 screened participants, 158 (60%) were randomly assigned to treatment (53 [34%] to placebo, 52 [33%] to empagliflozin 10 mg, and 53 [34%] to linagliptin). For the primary outcome, the adjusted mean HbA 1c change from baseline at week 26 was -0·84% [-9·2 mmol/mol] in the empagliflozin pooled group versus placebo (95% CI -1·50 to -0·19 [-16·4 to -2·1]; p=0·012); the corresponding change from baseline for linagliptin versus placebo was -0·34% [-3·8 mmol/mol; 95% CI -0·99 to 0·30 [-10·8 to 3·3]; p=0·29). Adverse events occurred in 34 (64%) participants in the placebo group, 40 (77%) in the empagliflozin pooled group, and 37 (71%) in the linagliptin group, up to week 26. Of these, severe adverse events were reported in two (4%) participants in the placebo group, one (2%) in the empagliflozin pooled group, and one (2%) in the linagliptin group. Hypoglycaemia was the most frequently reported adverse event with higher rates for those on active drug treatment compared with placebo. No severe hypoglycaemia cases were reported., Interpretation: Empagliflozin provided clinically relevant placebo-corrected reductions in HbA 1c , whereas linagliptin did not, and might offer a new treatment option for young people with type 2 diabetes., Funding: The Boehringer Ingelheim and Eli Lilly and Company Alliance., Competing Interests: Declaration of interests LML has received consulting fees from Provention, Dompe, Medtronic, Roche, Janssen, Eli Lilly, Dexcom, Novo Nordisk, and Vertex. TD has received speaker, advisory panel, or research support from AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, Insulet, Lifescan, Medtronic, Novo Nordisk, Roche, and Sanofi; and is a shareholder of DreaMed Diabetes. WVT has received consulting fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Medtronic Diabetes. SW has served on a data safety monitoring board for the National Institute of Diabetes and Digestive and Kidney Diseases/US National Institutes of Health; and served on an advisory panel or board for Roche Diagnostics and Medtronic MiniMed. PZ has consulted for Boehringer Ingelheim, Merck, Eli Lilly, Janssen, I-ACT, and Novo Nordisk. DN and JM are employees of Boehringer Ingelheim. GJK declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: To use continuous glucose monitoring (CGM)-based time-in-range (TIR) as a primary efficacy endpoint to compare the second-generation basal insulin (BI) analogues insulin glargine 300 U/ml (Gla-300) and insulin degludec 100 U/ml (IDeg-100) in adults with type 1 diabetes (T1D)., Materials and Methods: InRange was a 12-week, multicentre, randomized, active-controlled, parallel-group, open-label study comparing glucose TIR and variability between Gla-300 and IDeg-100 using blinded 20-day CGM profiles. The inclusion criteria consisted of adults with T1D treated with multiple daily injections, using BI once daily and rapid-acting insulin analogues for at least 1 year, with an HbA1c of 7% or higher and of 10% or less at screening., Results: Overall, 343 participants were randomized: 172 received Gla-300 and 171 IDeg-100. Non-inferiority (10% relative margin) of Gla-300 versus IDeg-100 was shown for the primary endpoint (percentage TIR ≥ 70 to ≤ 180 mg/dl): least squares (LS) mean (95% confidence interval) 52.74% (51.06%, 54.42%) for Gla-300 and 55.09% (53.34%, 56.84%) for IDeg-100; LS mean difference (non-inferiority): 3.16% (0.88%, 5.44%) (non-inferiority P = .0067). Non-inferiority was shown on glucose total coefficient of variation (main secondary endpoint): LS mean 39.91% (39.20%, 40.61%) and 41.22% (40.49%, 41.95%), respectively; LS mean difference (non-inferiority) -5.44% (-6.50%, -4.38%) (non-inferiority P < .0001). Superiority of Gla-300 over IDeg-100 was not shown on TIR. Occurrences of self-measured and CGM-derived hypoglycaemia were comparable between treatment groups. Safety profiles were consistent with known profiles, with no unexpected findings., Conclusions: Using clinically relevant CGM metrics, InRange shows that Gla-300 is non-inferior to IDeg-100 in people with T1D, with comparable hypoglycaemia and safety profiles., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Randomised controlled trials and other prospective clinical studies for novel medical interventions in people with diabetes have traditionally reported HbA 1c as the measure of average blood glucose levels for the 3 months preceding the HbA 1c test date. The use of this measure highlights the long-established correlation between HbA 1c and relative risk of diabetes complications; the change in the measure, before and after the therapeutic intervention, is used by regulators for the approval of medications for diabetes. However, with the increasing use of continuous glucose monitoring (CGM) in clinical practice, prospective clinical studies are also increasingly using CGM devices to collect data and evaluate glucose profiles among study participants, complementing HbA 1c findings, and further assess the effects of therapeutic interventions on HbA 1c . Data is collected by CGM devices at 1-5 min intervals, which obtains data on glycaemic excursions and periods of asymptomatic hypoglycaemia or hyperglycaemia (ie, details of glycaemic control that are not provided by HbA 1c concentrations alone that are measured continuously and can be analysed in daily, weekly, or monthly timeframes). These CGM-derived metrics are the subject of standardised, internationally agreed reporting formats and should, therefore, be considered for use in all clinical studies in diabetes. The purpose of this consensus statement is to recommend the ways CGM data might be used in prospective clinical studies, either as a specified study endpoint or as supportive complementary glucose metrics, to provide clinical information that can be considered by investigators, regulators, companies, clinicians, and individuals with diabetes who are stakeholders in trial outcomes. In this consensus statement, we provide recommendations on how to optimise CGM-derived glucose data collection in clinical studies, including the specific glucose metrics and specific glucose metrics that should be evaluated. These recommendations have been endorsed by the American Association of Clinical Endocrinologists, the American Diabetes Association, the Association of Diabetes Care and Education Specialists, DiabetesIndia, the European Association for the Study of Diabetes, the International Society for Pediatric and Adolescent Diabetes, the Japanese Diabetes Society, and the Juvenile Diabetes Research Foundation. A standardised approach to CGM data collection and reporting in clinical trials will encourage the use of these metrics and enhance the interpretability of CGM data, which could provide useful information other than HbA 1c for informing therapeutic and treatment decisions, particularly related to hypoglycaemia, postprandial hyperglycaemia, and glucose variability., Competing Interests: Declaration of interests TB has received honoraria for participation on advisory boards for Novo Nordisk, Sanofi, Eli Lilly, Boehringer-Ingelheim, Medtronic, and Indigo Diabetes, and as a speaker for AstraZeneca, Eli Lilly, Novo Nordisk, Medtronic, Sanofi, and Roche. TB owns stocks of DreaMed Diabetes and his institution (University Medical Centre Ljubljana, University Children's Hospital) has received research grant support and travel expenses from Abbott Diabetes Care, Medtronic, Novo Nordisk, Sanofi, Sandoz, Novartis. SAA has served on advisory boards for Novo Nordisk and Medtronic and has spoken at educational events sponsored by Novo Nordisk and Sanofi in the last 12 months. She is a co-investigator on the EU IMI Hypoglycaemia Redefining Solutions for Better Lives programme, which has the industry partners Abbott Diabetes Care, Eli Lilly, Medtronic, Novo Nordisk, and Sanofi-Aventis. RWB reports that his institution (Jaeb Center for Health Research) has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Eli Lilly and Novo Nordisk; and consulting fees from Insulet, Bigfoot Biomedical, vTv Therapeutics, and Diasome. RMB has received research support from Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, CeQur, Dexcom, Eli Lilly, Hygieia, Insulet, and Medtronic. RMB has received consulting fees from Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, CeQur, Dexcom, Eli Lilly, Hygieia, Insulet, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, United Healthcare, Vertex Pharmaceuticals, and Zealand Pharma. RMB has participated on advisory boards for Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, CeQur, Dexcom, Eli Lilly, Hygieia, Insulet, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, United Healthcare, Vertex Pharmaceuticals, and Zealand Pharma. BAB has received honoraria for participating in advisory boards for Novo Nordisk, Lilly, and Arecor. TD has received honoraria from Abbott, AstraZeneca, Boehringer, Dexcom, Lilly, Medtronic, Novo Nordisk, Roche, Sanofi, and Ypsomed. TD has received research support from Abbott, AstraZeneca, Boehringer, Dexcom, Lilly, Medtronic, Novo Nordisk, Roche, Sanofi, and Ypsomed. TD has received consulting fees from Abbott, AstraZeneca, Boehringer, Dexcom, Lilly, Medtronic, Novo Nordisk, Roche, Sanofi, and Ypsomed. TD is a shareholder of DreaMed Diabetes. RG has received honoraria as an advisor to Lark, Sweetch, and Vida. AC has received honoraria from AstraZeneca, Berlin Chemie, Merck, Novo Nordisk, and Roche Diagnostics. AC has received consulting fees from AstraZeneca, Bayer, Elsevier, Roche Diagnostics, Sevier, and Theras. AC has participated on advisory boards for Eli Lilly and Roche Diagnostics. EC has received speaker fees from Sanofi and Novartis, and institutional research support from Medtronic, Sanofi, and Powder Pharmaceuticals. PC has received honoraria for speaking from Medtronic, Dexcom, Abbott, Glooko, DreaMed, Novo Nordisk, Lilly, and Sanofi, and has received research support from Medtronic, Dexcom, Abbott, and Novo Nordisk. KLC receives subscription revenue for the web blog Close Concerns from Abbott, Biolinq, Dexcom, GlySens, Medtronic, Percusense, and Senseonics. SG has received advisory board honoraria and consulting fees from Bayer, Eli Lilly, Lifescan, Medtronic, Novo Nordisk, and Zealand. He has received research grants from Dario, Dexcom, Eli Lilly, JDFR, Lexicon, Medtronic, Merck, Novo Nordisk, Sanofi, and T1D Exchange. JC, JH, and JK are employees of the diaTribe Foundation, which receives funding support from continuous glucose monitor manufacturers Abbott Diabetes Care, Dexcom, and Medtronic. IBH receives consulting fees from Abbott Diabetes Care, Roche, Lifescan, and GWave, and receives research support from Insulet and Dexcom. LL has received consulting fees from Janssen, Insulet, Boehringer Ingelheim, Medtronic, Dompe, Provention, Eli Lilly, Roche, and Dexcom. LL has participated on advisory boards for Janssen, Insulet, Boehringer Ingelheim, Medtronic, Dompe, Provention, Eli Lilly, Roche, and Dexcom. BK has received honoraria as a speaker from Dexcom and Tandem and reports research support, managed by the University of Virginia, from Dexcom, Novo Nordisk, and Tandem Diabetes Care. BK receives patent royalties, managed by the University of Virginia, for US Patent numbers; #7,815,569 B2, #8,135,548 B2, #8,718,958 B2, #9,882,660 B2, #10,194,850, and #11,289,201. TK has received honoraria from Medtronic, Abbott, Insulet, DexCom, Tandem, Sanofi, Eli Lilly, Novo Nordisk, Merck and Janssen. TK has participated in advisory boards for Medtronic, Abbott, Insulet, Dexcom, Tandem, Sanofi, Eli Lilly, Novo Nordisk, Merck, and Janssen. She has received research support from Abbott and Sanofi. DMaa has consulted for Abbott, Aditxt, Biospex, Dompe, Eli Lilly, the Helmsley Charitable Trust, Insulet, Lifescan, Mannkind, Medtronic, Novo Nordisk, and Sanofi. He has received research support from the Helmsley Charitable Trust, the Juvenile Diabetes Research Foundation, the National Institutes of Health, the National Science Foundation, and his institution (Stanford Diabetes Research Center) has had research support from Dexcom, Insulet, Medtronic, and Tandem. CM has received honoraria from Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Imcyse, Insulet, Zealand Pharma, Avotres, Mannkind, Sandoz, and Vertex. CM has participated on advisory boards for Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Imcyse, Insulet, Zealand Pharma, Avotres, Mannkind, Sandoz, and Vertex. Financial compensation for these activities has been received by KU Leuven. CM has received research support through KU Leuven from Medtronic, Imcyse, Novo Nordisk, Sanofi, and ActoBio Therapeutics. DMau has received honoraria as a speaker and advisory board member for Almirall, Esteve, Ferrer, Janssen, Lilly, Menarini, Merck Sharp and Dohme, Novo Nordisk, and Sanofi. ER serves on advisory boards for Abbott, Air Liquide South Africa, Dexcom, Insulet, Sanofi, Roche Diabetes Care, Novo Nordisk, and Eli Lilly, and has received research support from Dexcom and Tandem. RNim has received speaking and consulting fees from Novo Nordisk, Eli Lilly, and DreaMed Diabetes. He has received research grants from the Helmsley Charitable Trust, Dexcom, Medtronic, Abbott Diabetes Care, and Insulet. RNim owns stock in DreaMed Diabetes. RNis has received honoraria as a speaker for Abbott, Astellas Pharma, Boehringer-Ingelheim, Eli Lilly, Kissei Pharmaceutical, Merck Sharp and Dohme, Medtronic, Novartis, Novo Nordisk, Sanofi, and Takeda. He has received both research fees and research expenses from Abbott, Boehringer-Ingelheim, Ono Pharmaceuticals, Taisho Pharmaceuticals, and Takeda. MS has received honoraria as a speaker and advisory board member from Pfizer, Medtronic, Abbott, Novo Nordisk, Merck, and Sanofi. He has received research grants from Novo Nordisk and is consultant doctor to Biomm and Cristalia. SDP declares grants from AstraZeneca and Boehringer Ingelheim; consulting fees from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hengrui Pharmaceutical, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi; honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi. JR has received consulting fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi, and fees for speaking for Eli Lilly, Novo Nordisk, and Sanofi. JR has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Hanmi, Sanofi, and Zealand and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, Hanmi, Novartis, Intarcia, Merck, Novo Nordisk, Oramed, Pfizer, and Sanofi. KU declares honoraria from Takeda, Novo Nordisk, Nippon, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, AstraZeneca, MSD, Ono, Sumitomo Pharma, Sanofi, Astellas. KU has received grant support from Takeda, Novo Nordisk, Eli Lilly, Nippon, Boehringer Ingelheim, Abbott Japan, Mitsubishi Tanabe Pharma, Merck Sharp and Dohme, Ono, Sumitomo Pharma, Sanofi, Kyowa Kirin, and Daiichi-Sankyo. GEU has received research support, managed by Emory University, from AstraZeneca, Bayer, and Dexcom. SAW has received honoraria from Abbott and Dexcom, has received consulting fees from Zealand, and has received research support for his institution (Sackler Faculty of Medicine, Tel Aviv University) from Abbott and Medtronic. MP has received honoraria for participation on advisory boards from AstraZeneca, Eli Lilly, Insulet, Mannkind, Medtronic Diabetes, Pfizer, Sanofi, and Dompé. MP has received consulting fees from Eli Lilly, Medtronic Diabetes, Novo Nordisk, Pfizer, Sanofi, and Qulab Medical. MP has received research grants from Dexcom, Eli Lilly, Insulet, Medtronic Diabetes, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi, DreaMed Diabetes, NG Solutions, Dompe, Lumos, GWAVE, and OPKO. MP owns stocks in DreaMed-Diabetes and NG Solutions. All other authors declare no competing interests. Support for the CGMs in Clinical Trials consensus meeting and development was provided by the Time in Range Coalition, Abbott Diabetes Care, Novo Nordisk, Dexcom, Eli Lilly, Apple Pickers Foundation, Diasome, Insulet Corporation, Lifescan, Medtronic, Sanofi, Vertex, Zealand Pharma, and Zucara. C-DISC, Embecta, and Novartis also provided funding to support the consensus meeting. The contents of this consensus statement represent the authors' views and do not constitute an official position of the National Institutes of Health or the United States Government., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally., Research Design and Methods: We analyzed data on 17,280 cases of T1D diagnosed during 2018-2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models., Results: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1-12.2) in 2018 to 21.7 (20.6-22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2-14.0) in 2018 to 26.7 (25.7-27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5-12.9) to 24.7 (24.0-25.5) for adolescents ages 12-18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018-2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic., Conclusions: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent., (© 2022 by the American Diabetes Association.)

Background: Continuous glucose monitoring (CGM) might have beneficial effects on glycemic control and body mass index (BMI) in adults with type 1 (T1D) or type 2 diabetes (T2D). Methods: The diabetes prospective follow-up registry was used to identify individuals with T1D or T2D ≥18 years starting CGM management in 2015 or later and follow-up information available. Hemoglobin A1c (HbA1c), BMI, and event rates of severe hypoglycemia in the year before CGM start were compared with two follow-up periods: (1) CGM use for 3-6 months and (2) CGM use for >6 months. Repeated measurements linear and negative binomial regressions were used (adjustment for sex, age at diabetes onset, and baseline parameters) and stratified by diabetes type. Results: Mean follow-up time was 1.8 years in T1D ( n  = 2994) and 1.9 years in T2D ( n  = 1440). In T1D, adjusted mean HbA1c decreased significantly from 7.65% (95% confidence interval: 7.62-7.68) at baseline to 7.54% (7.51-7.57) during follow-up. BMI increased slightly (baseline: 25.4 kg/m 2 [25.3-25.5], follow-up >6 months: 25.8 kg/m 2 [25.7-25.9]), whereas event rates of severe hypoglycemia were significantly lower after >6 months with CGM (9.0 events/100 patient-years [PY; 8.0-10.1]) compared with baseline (11.3 events/100 PY [10.4-12.2]) in adults with T1D. In T2D, HbA1c decreased from 7.21% (7.17%-7.25%) to 7.00% (6.95%-7.04%) and BMI did not change after CGM initiation. Conclusion: Our results provide real-world evidence on CGM management in adult individuals with T1D or T2D. We suggest strengthening patients' and physicians' readiness toward diabetes technology in T2D and more openness of health insurance to cover cost based on proven benefits.

Purpose: In Europe, >2 million individuals with familial hypercholesterolemia (FH) are currently undiagnosed. Effective screening strategies for FH diagnosis in childhood are urgently needed. We assessed the overall performances of 2 different FH screening programs in children: universal screening program with opt-out and opt-in type participation., Methods: We analyzed the data from 2 independent populations based on >166,000 individuals screened for hypercholesterolemia. Genetic analyses of FH-related genes were finalized in 945 children and 99 parents., Results: A total of 305 (32.3%) children were genotyped as positive or with a variant of uncertain significance in FH-related genes. For low-density lipoprotein cholesterol levels of 3.5 mmol L (135.3 mg/dL), the overall sensitivity and specificity for confirming FH were 90.5% and 55.3%, respectively. As part of child-parent screening, in >90% of the families, the parent with reported higher cholesterol levels was positive for the familial genetic variant. The cohort-based prevalence of FH from the opt-out universal screening program was estimated to be 1 in 431 individuals (95% CI = 1/391-1/472)., Conclusion: Universal 3-step FH screening approach in children enabled detection of most children and their parents in every generation screened at reasonable costs. Opt-out screening strategy might be preferable over opt-in screening strategy., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Competing Interests: TK Speakers Honoraria Lilly, Merck Serono.

Short-term glycemic variability is associated with the risk of hypoglycemia and hyperglycemia in people living with type 1 diabetes and can potentially affect clinical outcomes. Continuous glucose monitoring (CGM) is of increasing importance to evaluate glycemic variability in greater detail. Specific metrics for assessing glycemic variability were proposed, such as the SD of mean glucose level and associated coefficient of variation, and time in target glucose range to guide study designs, therapy and allow people with diabetes more transparency in interpreting their own CGM data. Randomized controlled trials (RCT) and real-world evidence provide complementary information about the efficacy/effectiveness and safety of interventions. Insulin glargine 300 U/mL (Gla-300) has a longer lasting and less variable action than insulin glargine U100 (Gla-100) with a lower risk of hypoglycemia. While insulin degludec U100 (iDeg-100) was associated with lower glucose values but more time below range in one randomized study compared with Gla-300, Gla-300 was associated with a higher per cent time in range, but also above the therapeutic range. However, a real-world study did not find differences during the day between Gla-300 and iDeg-100. The upcoming InRange RCT is the first head-to-head comparison of Gla-300 with iDeg-100 using CGM in an international population using CGM metrics as the primary endpoint. The non-interventional COMET-T real-world study will determine the real-world effectiveness of Gla-300 using CGM metrics and cover a broad spectrum of clinical practice decisions irrespective of the prior basal insulin., Competing Interests: Competing interests: JKM is a member of the advisory board of Abbott Diabetes Care, Boehringer Ingelheim, Becton-Dickinson, Eli Lilly, Medtronic, Novo Nordisk, Prediktor, Roche Diabetes Care, and Sanofi-Aventis and received speaker honoraria from Abbott Diabetes Care, AstraZeneca, Becton-Dickinson, DexCom, Eli Lilly, MSD, Novo Nordisk, Roche Diabetes Care, Sanofi, and Servier. JKM is a shareholder of decide Clinical Software. TD has received speaker’s honoraria and research support from or has consulted for Abbott, AstraZeneca, Boehringer, DexCom, Lilly, Medtronic, Novo Nordisk, Roche, Sanofi and Ypsomed and is a shareholder of DreaMed Ltd. SG has received speaker’s honoraria from Sanofi, Eli Lilly, Novo Nordisk, Abbott Diabetes Care, AstraZeneca, DexCom, VitalAire, Berlin Chemie-Menarini, Pfizer, MSD, Ascensia, and Amgen and has consulted for Abbott Diabetes Care, Roche, Medtronic, Berlin Chemie-Menarini and EvivaMed. SG has volunteered for the German Diabetes Society (Deutsche Diabetes Gesellschaft) and Diabetology Working Group Baden-Württemberg (Arbeitsgemeinschaft Diabetologie Baden-Württemberg). SB is a member of the advisory board of Amgen, Novartis, Sanofi, Novo Nordisk, and Daiichi Sankyo and has received speaker’s honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, and Sanofi. PB has received research funding and honoraria for consultancy from a number of companies including AstraZeneca, Bayer, Boehringer, Roche, and Sanofi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)