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Background : Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods : An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results : The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion : The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

The concept of maintaining blood glucose levels within the 70-180 mg/dL range, known as time-in-range, has raised questions regarding its representation of true physiological euglycemia. Some have speculated that focusing on the time spent within the 70-140 mg/dL range, introduced as time in tight range (TITR) through the International Consensus statement, could serve as a more precise metric for assessing normoglycemia in individuals with type 1 diabetes. This article delves into the current status of TITR as an emerging marker and explores how advanced hybrid closed-loop systems may offer a promising avenue for achieving this higher level of glycemic control.

Physical activity and exercise have many beneficial effects on general and type 1 diabetes (T1D) specific health and are recommended for individuals with T1D. Despite these health benefits, many people with T1D still avoid exercise since glycemic management during physical activity poses substantial glycemic and psychological challenges - which hold particularly true for unannounced exercise when using an AID system. Automated insulin delivery (AID) systems have demonstrated their efficacy in improving overall glycemia and in managing announced exercise in numerous studies. They are proven to increase time in range (70-180 mg/dL) and can especially counteract nocturnal hypoglycemia, even when evening exercise was performed. AID-systems consist of a pump administering insulin as well as a CGM sensor (plus transmitter), both communicating with a control algorithm integrated into a device (insulin pump, mobile phone/smart watch). Nevertheless, without manual pre-exercise adaptions, these systems still face a significant challenge around physical activity. Automatically adapting to the rapidly changing insulin requirements during unannounced exercise and physical activity is still the Achilles' heel of current AID systems. There is an urgent need for improving current AID-systems to safely and automatically maintain glucose management without causing derailments - so that going forward, exercise announcements will not be necessary in the future. Therefore, this narrative literature review aimed to discuss technological strategies to how current AID-systems can be improved in the future and become more proficient in overcoming the hurdle of unannounced exercise. For this purpose, the current state-of-the-art therapy recommendations for AID and exercise as well as novel research approaches are presented along with potential future solutions - in order to rectify their deficiencies in the endeavor to achieve fully automated AID-systems even around unannounced exercise.

Objective: To evaluate the use of faster acting (FIA) and standard insulin aspart (SIA) with hybrid automated insulin delivery (AID) in active youth with type 1 diabetes. Research Design and Methods: In this double-blind multinational randomized crossover trial, 30 children and adolescents with type 1 diabetes (16 females; aged 15.0 ± 1.7 years; baseline HbA1c 7.5% ± 0.9% [58 ± 9.8 mmol/mol]) underwent two unrestricted 4-week periods using hybrid AID with either FIA or SIA in random order. During both interventions, participants were using the hybrid AID (investigational version of MiniMed™ 780G; Medtronic). Participants were encouraged to exercise as frequently as possible, capturing physical activity with an activity monitor. The primary outcome was the percentage of sensor glucose time above range (180 mg/dL [10.0 mmol/L]) measured by continuous glucose monitoring. Results: In an intention-to-treat analysis, mean time above range was 31% ± 15% at baseline, 19% ± 6% during FIA use, and 20% ± 6% during SIA use with no difference between treatments: mean difference = -0.9%; 95% CI: -2.4% to 0.6%; P  = 0.23. Similarly, there was no difference in mean time in range (TIR) (78% and 77%) or median time below range (2.5% and 2.8%). Glycemic outcomes during exercise or postprandial periods were comparable for the two treatment arms. No severe hypoglycemia or diabetic ketoacidosis events occurred. Conclusions: FIA was not superior to SIA with hybrid AID system use in physically active children and adolescents with type 1 diabetes. Nonetheless, both insulin formulations enabled high overall TIR and low time above and below ranges, even during and after documented exercise. Trial Registration Clinicaltrials.gov: NCT04853030.

The Medtronic advanced hybrid closed-loop (AHCL) and MiniMed™ 670G hybrid closed-loop (HCL) systems provide the option to temporarily increase the glucose target to 150 mg/dL (8.3 mmol/L). This analysis investigated the efficacy of the AHCL compared with that of the HCL after the use of this setting. Data from 60 participants in the Fuzzy Logic Automated Insulin Regulation (FLAIR) study were used to compare the AHCL and HCL systems after the use of the temporary target (TT), and during analogous periods where this setting was not used. Differences in time in range 70-180 mg/dL between the systems were similar after the use of the TT setting and during analogous non-TT periods (interaction P  = 0.87). Similar trends were observed for mean glucose, percentage time >180 mg/dL, and percentage time >250 mg/dL. Differences between AHCL and HCL systems were similar after the use of the TT setting compared with those of non-TT periods. ClinicalTrials.gov NCT03040414.

Suicide is the leading cause of death among young people aged 20-34 and the second leading cause of death in adolescents aged 15-19. In the general population, among those attempting suicide 7% die by suicide and 23% reattempt with nonfatal consequences. Depression, closely associated with suicidal ideation, is diagnosed in 7%-25% of the United States and European populations. Individuals with type 1 diabetes (T1D) have a two to three times higher prevalence of depression and approximately double the rate of suicide compared to the general population. Rates of self-harm and suicide among people with diabetes are likely to be considerably underestimated due to poor identification. This information is critical to create interventions to decrease rates of suicide and self-harm. This is particularly important in the setting of advanced technologies in T1D, which offer both easier methods of self-injurious behaviors through insulin misuse and can act as identification tools to identify risk insulin behaviors and provide opportunities to develop interventions and prevention efforts in those with depression and suicidal ideation/behavior/acts. To this end, our goal was to identify any literature on coding diabetes correctly in individuals who die by suicide or engage in intentional self-harm. Furthermore, to describe the Reducing Suicide Rates Among Individuals with Diabetes (RESCUE) Collaborative Community and its goals of using multiple approaches to reduce rates of intended self-injury and suicide among people with diabetes. These include detection of cases, understanding support needs, identification of risk factors, and early intervention for individuals at risk.

Background: The MiniMed™ 780G system includes an advanced hybrid closed loop (AHCL) algorithm that provides both automated basal and correction bolus insulin delivery. The preliminary performance of the system in real-world settings was evaluated. Methods: Data uploaded from August 2020 to March 2021 by individuals living in Belgium, Finland, Italy, the Netherlands, Qatar, South Africa, Sweden, Switzerland, and the United Kingdom were aggregated and retrospectively analyzed to determine the mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR), and above (TAR) glycemic ranges, system use, and insulin consumption in users having ≥10 days of sensor glucose (SG) data after initiating AHCL. The impact of initiating AHCL was evaluated in a subgroup of users also having ≥10 days of SG data, before AHCL initiation. Results: Users ( N  = 4120) were observed for a mean of 54 ± 32 days. During this time, they spent a mean of 94.1% ± 11.4% of the time in AHCL and achieved a mean GMI of 6.8% ± 0.3%, TIR of 76.2% ± 9.1%, TBR <70 of 2.5% ± 2.1%, and TAR >180 of 21.3% ± 9.4%, after initiating AHCL. There were 77.3% and 79.0% of users who achieved a TIR >70% and a GMI of <7.0%, respectively. Users for whom comparison with pre-AHCL was possible ( N  = 812) reduced their GMI by 0.4% ± 0.4% ( P  = 0.005) and increased their TIR by 12.1% ± 10.5% ( P  < 0.0001), post-AHCL initiation. More users achieved the glycemic treatment goals of GMI <7.0% (37.6% vs. 75.2%, P  < 0.0001) and TIR >70% (34.6% vs. 74.9%, P  < 0.0001) when compared with pre-AHCL initiation. Conclusion: Most MiniMed 780G system users achieved TIR >70% and GMI <7%, while minimizing hypoglycemia, in a real-world condition.

Background: Development of coordinated management approaches is important to facilitate self-care in people with diabetes (PwD). Gaining a better understanding of suboptimal insulin use is key in this endeavor. This review aimed, for the first time, to systematically identify and narratively summarize real-world evidence on the extent of suboptimal insulin use (missed and mistimed insulin) in PwD. Methods: A systematic literature search of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews identified studies reporting on missed and mistimed insulin dosing. Results: From 3305 studies, 37 publications reporting on 30 unique studies that involved 58,617 PwD were included. Studies were conducted across 12 different countries and most employed cross-sectional surveys. Observations regarding missed and mistimed insulin doses were reported in 25 and 10 studies, respectively. PwD reported missing insulin doses, but rates varied due to differences in reporting methods, participant populations, and insulin regimens. The association between missed dosing and glycemic control was evaluated in ten studies in which the authors reported lower glycated hemoglobin (HbA1c) levels in PwD who did not omit insulin. The proportion of PwD reporting mistiming of insulin was in the range of 20-45%, depending on the study; this was associated with higher rates of hypoglycemia and higher HbA1c as reported by study authors. Reasons for suboptimal insulin use were multifactorial, occurring due to disrupted daily routines, social situations, and hypoglycemia avoidance. Conclusions: This review suggests that suboptimal insulin use is widespread and that PwD using insulin may still be struggling with disease management. There is an unmet need for better integrated support in managing the complexities of insulin therapy and for the development of systems (e.g. digital solutions) that empower people to take control of insulin-treated diabetes.

Objective: The international SWEET registry (NCT04427189) was initiated in 2008 to improve outcomes in pediatric diabetes. A 10-year follow-up allowed studying time trends of key quality indicators in 22 centers from Europe, Australia, Canada, and India in youth with type 1 diabetes (T1D). Methods: Aggregated data per person with T1D <25 years of age were compared between 2008-2010 and 2016-2018. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration groups. Results: The first and second time periods included 4930 versus 13,654 persons, 51% versus 52% male, median age 11.3 [Q1; Q3: 7.9; 14.5] versus 13.3 [9.7; 16.4] years, and T1D duration 2.9 [0.8; 6.4] versus 4.2 [1.4; 7.7] years. The adjusted hemoglobin A1C (HbA1c) improved from 68 (95% confidence interval [CI]: 66-70) to 63 (60; 65) mmol/mol ( P  < 0.0001) or 8.4 (95% CI: 8.2-8.6) to 7.9 (7.6; 8.1) % ( P  < 0.0001). Across all age groups, HbA1c was significantly lower in pump and sensor users. Severe hypoglycemia declined from 3.8% (2.9; 5.0) to 2.4% (1.9; 3.1) ( P  < 0.0001), whereas diabetic ketoacidosis events increased significantly with injection therapy only. Body mass index-standard deviation score also showed significant improvements 0.55 (0.46; 0.64) versus 0.42 (0.33; 0.51) ( P  < 0.0001). Over time, the increase in pump use from 34% to 44% preceded the increase in HbA1c target achievement (<53 mmol/mol) from 21% to 34%. Conclusions: Twice yearly benchmarking within the SWEET registry was associated with significantly improved HbA1c on a background of increasing pump and sensor use for 10 years in young persons with T1D. Trial Registration: NCT04427189.

The increasing prevalence of diabetes, combined with a growing global shortage of health care professionals (HCP), necessitates the need to develop new approaches to diabetes care delivery to expand access to care, lessen the burden on people with diabetes, improve efficiencies, and reduce the unsustainable financial liability on health systems and payers. Use of digital diabetes technologies and telehealth protocols within a digital/virtual diabetes clinic has the potential to address these challenges. However, several issues must be resolved to move forward. In February 2020, organizers of the Advanced Technologies & Treatments for Diabetes Annual Conference convened an international panel of HCP, researchers, patient advocates, and industry representatives to review the status of digital diabetes technologies, characterize deficits in current technologies, and identify issues for consideration. Since that meeting, the importance of using telehealth and digital diabetes technologies has been demonstrated amid the global coronavirus disease (COVID-19) pandemic. This article summarizes the panel's discussion of the opportunities, obstacles, and requisites for advancing the use of these technologies as a standard of care for the management of diabetes.

Many people with insulin-treated diabetes continue to experience inadequate glycemic control and a high incidence of hypoglycemic events, despite improvements in therapeutic strategies. While glycated hemoglobin (HbA 1c ) is currently recognized as the gold-standard for assessing glycemic control, the measure reflects mean blood glucose levels over a period of time, does not inform on acute glycemic deviations, and can be unreliable in certain populations. Continuous glucose monitoring (CGM) facilitates the acquisition of blood glucose data around the clock and, importantly, predicts and/or captures acute hyper- and hypoglycemic episodes. In light of the recent publication of the Time in Range (TIR) International Consensus Group report on key CGM metrics, we performed a review of current CGM evidence for second-generation basal insulins in both people with type 1 and type 2 diabetes. The identified studies highlight the varied CGM-related metrics used to assess basal insulins, which complicate comparisons. Furthermore, all studies had small sample sizes and typically were of short duration, which may account for the lack of statistically significant between-treatment differences observed. Differences were seen in the titration approaches used and the settings in which participants were observed. These results highlight the need for further studies of second-generation basal insulin analogs that are designed to capture the standard metrics proposed by the TIR consensus group, with additional consideration given to sample size and study duration.

Background: The prevalence of type 2 diabetes (T2D) in youth is increasing. Treatment options beyond metformin and insulin are needed. The safety, tolerability, pharmacokinetics, and pharmacodynamics of liraglutide once daily in youth (10-17 years old) with T2D were investigated in a randomized, double-blind, placebo-controlled trial., Subjects and Methods: Youth treated with diet/exercise alone or with metformin and having a hemoglobin A1c (HbA1c) level of 6.5-11% were randomized to liraglutide (n=14) or placebo (n=7). Starting at 0.3 mg/day, doses were escalated weekly to 0.6, 0.9, 1.2, and 1.8 mg/day (or placebo equivalent) for 5 weeks., Results: Nineteen participants completed the trial. Baseline characteristics were similar between groups, with mean (SD) values for age of 14.8 (2.2) years, weight of 113.2 (35.6) kg (range, 57-214 kg), diabetes duration of 1.7 (1.4) years, and HbA1c level of 8.1% (1.2%). No serious adverse events (AEs), including severe hypoglycemia, occurred. Transient gastrointestinal AEs were most common at lower liraglutide doses during dose escalation. No significant changes in safety and tolerability parameters occurred. There was no evidence of pancreatitis or lipase elevations above three times the upper normal limit; calcitonin levels remained within the normal range. For liraglutide 1.8 mg, mean half-life was 12 h, and clearance was 1.7 L/h. After 5 weeks, the decline in HbA1c level was greater with liraglutide versus placebo (-0.86 vs. 0.04%, P=0.0007), whereas mean body weight remained stable (-0.50 vs. -0.54 kg, P=0.9703)., Conclusions: Liraglutide was well tolerated in youth with T2D, with safety, tolerability, and pharmacokinetic profiles similar to profiles in adults.

Background: This study estimated temporal trends of metabolic control over 12 years in a national cohort of childhood-onset type 1 diabetes., Subjects and Methods: Data from the prospective childhood-onset diabetes register, which included 886 case subjects from 0 to 17.99 years of age at diagnosis and at least 1 year of follow-up until the age of 22.99 years, were analyzed using multivariable linear and logistic regression models in the observational period between 2000 and 2011., Results: Hemoglobin A1c (HbA1c) significantly decreased over 12 years, from 78 mmol/mol (interquartile range [IQR], 68-88 mmol/mol) (9.26% [IQR, 8.41-10.24%]) in the year 2000 to 61 mmol/mol (IQR, 55-67 mmol/mol) (7.75% [IQR, 7.20-8.30%]) in the year 2011 (P<0.001). HbA1c was significantly associated with age, treatment modality, and duration of diabetes (P<0.001), with females having on average 1.02% higher HbA1c (P=0.01; 95% confidence interval [CI] 1.005-1.035). The overall use of insulin pumps was 74%. The incidence rate of severe acute complications was low: 1.07 per 100 patient-years for severe diabetic ketoacidosis (95% CI 0.81-1.40) and 1.21 per 100 patient-years for severe (requiring intravenous or intramuscular therapy) hypoglycemia (95% CI 0.81-1.40)., Conclusions: The metabolic control of the entire nationwide pediatric type 1 diabetes population significantly improved during the 12-year observational period with a low rate of severe acute complications events. The improvement was associated with the treatment modality. Additional efforts and solutions are necessary to further improve metabolic control and the quality of life of young people with type 1 diabetes.

Background: Compared with multiple daily injections (MDI), sensor-augmented pump (SAP) insulin therapy may reduce glycemic variability and oxidative stress in type 1 diabetes in a glycosylated hemoglobin (A1C)-independent manner., Subjects and Methods: The STAR 3 study compared SAP with MDI therapy for 1 year. Week-long continuous glucose monitoring studies were conducted at baseline and 1 year for assessment of glycemic variability in both groups. Soluble CD40 ligand (CD40L), a biomarker of inflammation and thrombocyte function, was measured at baseline and 1 year. Subjects were classified according to treatment group and 1-year A1C levels (<6.5%, 6.5-6.9%, 7-7.9%, ≥8%). Glycemic parameters were compared between SAP and MDI subjects in each A1C cohort., Results: At 1 year, sensor glucose values at A1C levels ≥6.5% were similar in the SAP and MDI groups. However, sensor glucose SD and coefficient of variation (CV) values were lower at A1C levels <8% among SAP than among MDI subjects; the overall between-group difference was significant for both SD (P<0.01) and CV (P=0.01). The overall mean amplitude of glycemic excursion was similar in MDI and SAP groups (P=0.23). CD40L levels fell over the course of the study in both groups, but the between-group difference was not significant (P=0.18). CD40L concentrations were unrelated to A1C, change in A1C from baseline, or glycemic variability., Conclusions: At comparable A1C levels of <8%, SAP reduced glycemic variability as measured by SD and CV compared with MDI. SAP may provide beneficial reductions in the number and severity of glycemic excursions.

Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been shown to display beneficial effects on glycemic control. SMBG is not only associated with a reduction of hemoglobin A1c but has also been demonstrated to increase patients' awareness of the disease. SMBG has also the potential to visualize and predict hypoglycemic episodes. International guidelines by the International Diabetes Federation, the European Society of Cardiology, and the European Association for the Study of Diabetes and also the International Society for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of self-management. More recently, two European consensus documents have been published to give recommendations for frequency and timing of SMBG also for various clinical scenarios. Recently, a European expert panel was held to further facilitate and enhance standardized approaches to SMBG. The aim was to present simple, clinically meaningful, and standardized SMBG strategies for type 2 diabetes. The panel recommended a less intensive and an intensive scheme for SMBG across the type 2 diabetes continuum. The length and frequency of SMBG performance depend on the clinical circumstances and the quality of glycemic control. The expert panel also recommended further evaluation of various schemes for SMBG in type 2 diabetes in clinical studies.

Background: studies investigating the effect of real-time continuous glucose monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1 diabetes are increasing. Pump therapy is well established as a "gold standard" for insulin delivery, offering improvements over multiple daily insulin injections. However, there is still a proportion of subjects using continuous subcutaneous insulin infusion in whom goals for metabolic control are far from achieved or benefits of this type of insulin therapy are transient. The SWITCH (Sensing With Insulin pump Therapy to Control HbA(1c) [hemoglobin A1c]) study is a multicenter, randomized, controlled, crossover study to evaluate if adding CGM to experienced pump patients with suboptimal metabolic control will provide additional insight enabling clinical and therapeutic benefit., Methods: subjects meeting the inclusion criteria were randomized to Sensor On or Sensor Off arms for 6 months, after a 1-month run-in period. Following a 4-month washout period, the subjects crossed over to the other study arm for 6 months. The primary end point was the between arm difference in HbA(1c) levels. Among others, additional end points include time spent in different glycemic ranges, percentage of patients with HbA(1c) <7%, number of hypoglycemic events, glucose variability parameters, safety outcomes, treatment satisfaction, and quality of life., Results: recruitment occurred between January 2008 and February 2009. A total of 153 patients were randomized. Study completion is anticipated in July 2010., Conclusions: the results will establish if adding CGM to existing, capable, insulin pump users can enable better metabolic control.

Background: Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes., Methods: Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments., Results: A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010., Conclusions: Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.