A narrative commentary about interoperability in medical devices and data used in diabetes therapy from an academic EU/UK/US perspective.

People living with diabetes have many medical devices available to assist with disease management. A critical aspect that must be considered is how systems for continuous glucose monitoring and insulin pumps communicate with each other and how the data generated by these devices can be downloaded, integrated, presented and used. Not only is interoperability associated with practical challenges, but also devices must adhere to all aspects of regulatory and legal frameworks. Key issues around interoperability in terms of data ownership, privacy and the limitations of interoperability include where the responsibility/liability for device and data interoperability lies and the need for standard data-sharing protocols to allow the seamless integration of data from different sources. There is a need for standardised protocols for the open and transparent handling of data and secure integration of data into electronic health records. Here, we discuss the current status of interoperability in medical devices and data used in diabetes therapy, as well as regulatory and legal issues surrounding both device and data interoperability, focusing on Europe (including the UK) and the USA. We also discuss a potential future landscape in which a clear and transparent framework for interoperability and data handling also fulfils the needs of people living with diabetes and healthcare professionals.

Associations of bolus insulin injection frequency and smart pen engagement with glycaemic control in people living with type 1 diabetes.

AIM: To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). MATERIALS AND METHODS: Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. RESULTS: Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. CONCLUSIONS: Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.

The Determination of Diabetes Utilities, Costs, and Effects Model: A Cost-Utility Tool Using Patient-Level Microsimulation to Evaluate Sensor-Based Glucose Monitoring Systems in Type 1 and Type 2 Diabetes: Comparative Validation.

OBJECTIVES: To assess the accuracy and validity of the Determination of Diabetes Utilities, Costs, and Effects (DEDUCE) model, a Microsoft-Excel-based tool for evaluating diabetes interventions for type 1 and type 2 diabetes. METHODS: The DEDUCE model is a patient-level microsimulation, with complications predicted based on the Sheffield and Risk Equations for Complications Of type 2 diabetes models for type 1 and type 2 diabetes, respectively. For this tool to be useful, it must be validated to ensure that its complication predictions are accurate. Internal, external, and cross-validation was assessed by populating the DEDUCE model with the baseline characteristics and treatment effects reported in clinical trials used in the Fourth, Fifth, and Ninth Mount Hood Diabetes Challenges. Results from the DEDUCE model were evaluated against clinical results and previously validated models via mean absolute percentage error or percentage error. RESULTS: The DEDUCE model performed favorably, predicting key outcomes, including cardiovascular disease in type 1 diabetes and all-cause mortality in type 2 diabetes. The model performed well against other models. In the Mount Hood 9 Challenge comparison, error was below the mean reported from comparator models for several outcomes, particularly for hazard ratios. CONCLUSIONS: The DEDUCE model predicts diabetes-related complications from trials and studies well when compared with previously validated models. The model may serve as a useful tool for evaluating the cost-effectiveness of diabetes technologies.

Use of insulin pumps and closed-loop systems among people living with diabetes: A narrative review of clinical and cost-effectiveness to enable access to technology and meet the needs of payers.

The use of continuous subcutaneous insulin infusion (CSII) via insulin pumps is today considered standard of care for type 1 diabetes (T1D). Closed-loop systems combining continuous glucose monitoring with automated algorithm-driven insulin delivery have been shown to be safe and efficacious in randomized controlled trials and real-life studies in both paediatric and adult participants with T1D. Implementation of hybrid closed-loop (HCL) systems has shown incremental effectiveness, with further reduction of hypoglycaemia and hyperglycaemia. Although less extensively studied in type 2 diabetes (T2D), insulin pumps have demonstrated their effectiveness in glucose control, along with a reduction in need for insulin and a neutral effect on weight. Recent studies have also shown promising results with the use of HCL systems in T2D. Cost-effectiveness studies in both T1D and T2D have shown that pump use is cost-effective in several countries, leading to improvements in quality-adjusted life-years. Insulin pumps are currently reimbursed for T1D in many European countries, but in only a few for individuals with T2D. HCL systems are to be evaluated in future trials performed in T2D to compare their incremental efficacy and cost-effectiveness in comparison with available intensification tools which include multiple daily insulin injections, metformin, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. There is a need for updated guidelines for the use of CSII and HCL in individuals living with T2D based on the emerging evidence, with identification of and recommendations for the people who would benefit the most, which would eventually form a basis for reimbursement and health policies.

Burden of established cardiovascular disease in people with type 2 diabetes and matched controls: Hospital-based care, days absent from work, costs and mortality.

AIMS: To assess hospital-based care, work absence, associated costs, and mortality in patients with type 2 diabetes with and without established cardiovascular disease (eCVD) compared to matched controls. MATERIALS AND METHODS: In a population-based cohort study, we analysed individual-level data from national health, social insurance and socio-economic registers for people diagnosed with type 2 diabetes before age 70 years and controls (5:1) in Sweden. Regression analysis was used to attribute costs and days absent due to eCVD. Mortality was analysed using Cox proportional hazard regression, stratified by birth year and adjusted for sex and education. RESULTS: Thirty percent (n = 136 135 of 454 983) of people with type 2 diabetes had ≥1 person-year with eCVD (women 24%; men 34%). The mean annual costs of hospital-based care for diabetes complications were EUR 2629 (95% confidence interval [CI] 2601-2657) of which EUR 2337 (95% CI 2309-2365) were attributed to eCVD (89%). The most costly person-years (10th percentile) were observed in a broad subgroup, 42% of people with type 2 diabetes and eCVD. People with type 2 diabetes had on average 146 days absent (95% CI 145-147) per year, of which 68 days (47%; 95% CI 67-70) were attributed to eCVD. The mortality hazard ratio for type 2 diabetes with eCVD was 4.63 (95%CI 4.58-4.68) and without eCVD was 1.86 (95% CI 1.84-1.88) compared to controls without eCVD. CONCLUSION: The sizable burden of eCVD on both the individual with type 2 diabetes and society calls for efficient management in order to reduce the risks for those living with eCVD and to postpone its onset.

Model-based predictions on health benefits and budget impact of implementing empagliflozin in people with type 2 diabetes and established cardiovascular disease.

AIM: To perform a model-based analysis of the short- and long-term health benefits and costs of further increased implementation of empagliflozin for people with type 2 diabetes and established cardiovascular disease (eCVD) in Sweden. MATERIALS AND METHODS: The validated Institute for Health Economics Diabetes Cohort Model (IHE-DCM) was used to estimate health benefits and a 3-year budget impact, and lifetime costs per quality-adjusted life years (QALY) gained of increased implementation of adding empagliflozin to standard of care (SoC) for people with type 2 diabetes and eCVD in a Swedish setting. Scenarios with 100%/75%/50% implementation were explored. Analyses were based on 30 model cohorts with type 2 diabetes and eCVD (n = 131 412 at baseline) from national health data registers. Sensitivity analyses explored the robustness of results. RESULTS: Over 3 years, SoC with empagliflozin (100% implementation) versus SoC before empagliflozin resulted in 7700 total life years gained and reductions in cumulative incidence of cardiovascular deaths by 30% and heart failures by 28%. Annual costs increased by 15% from higher treatment costs and increased survival. Half of these benefits and costs are not yet reached with current implementation below 50%. SoC with empagliflozin yielded 0.37 QALYs per person, with an incremental cost-effectiveness ratio of 16 000 EUR per QALY versus SoC before empagliflozin. CONCLUSIONS: Model simulations using real-world data and trial treatment effects indicated that a broader implementation of empagliflozin, in line with current guidelines for treatment of people with type 2 diabetes and eCVD, would lead to further benefits even from a short-term perspective.

Real-world performance of the MiniMed™ 670G system in Europe.

AIM: To evaluate the real-world performance of the MiniMed 670G system in Europe, in individuals with diabetes. MATERIALS AND METHODS: Data uploaded from October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analysed. The mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycaemic ranges, system use and insulin consumed in users with 10 or more days of sensor glucose data after initial Auto Mode start were determined. Another analysis based on suboptimally (GMI > 8.0%) and well-controlled (GMI < 7.0%) glycaemia pre-Auto Mode initiation was also performed. RESULTS: Users (N = 14 899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0% ± 0.4%, TIR of 72.0% ± 9.7%, TBR less than 3.9 mmol/L of 2.4% ± 2.1% and TAR more than 10 mmol/L of 25.7% ± 10%, after initiating Auto Mode. When compared with pre-Auto Mode initiation, GMI was reduced by 0.3% ± 0.4% and TIR increased by 9.6% ± 9.9% (P < .0001 for both). Significantly improved glycaemic control was observed irrespective of pre-Auto Mode GMI levels of less than 7.0% or of more than 8.0%. While the total daily dose of insulin increased for both groups, a greater increase was observed in the latter, an increase primarily due to increased basal insulin delivery. By contrast, basal insulin decreased slightly in well-controlled users. CONCLUSIONS: Most MiniMed 670G system users in Europe achieved TIR more than 70% and GMI less than 7% while minimizing hypoglycaemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.

Costs of diabetes complications: hospital-based care and absence from work for 392,200 people with type 2 diabetes and matched control participants in Sweden.

AIMS/HYPOTHESIS: The risk of complications and medical consequences of type 2 diabetes are well known. Hospital costs have been identified as a key driver of total costs in studies of the economic burden of type 2 diabetes. Less evidence has been generated on the impact of individual diabetic complications on the overall societal burden. The objective of this study was to analyse costs of hospital-based healthcare (inpatient and outpatient care) and work absence related to individual macrovascular and microvascular complications of type 2 diabetes in Sweden in 2016. METHODS: Data for 2016 were retrieved from a Swedish national retrospective observational database cross-linking individual-level data for 1997-2016. The database contained information from population-based health, social insurance and socioeconomic registers for 392,200 people with type 2 diabetes and matched control participants (5:1). Presence of type 2 diabetes and of diabetes complications were derived using all years, 1997-2016. Costs of hospital-based care and of absence from work due to diabetes complications were estimated for the year 2016. Regression analysis was used for comparison with control participants to attribute absence from work to individual complications, and to account for joint presence of complications. RESULTS: Use of hospital care for complications was higher in type 2 diabetes compared with control participants in 2016: 26% vs 12% had ≥1 hospital contact; there were 86,104 vs 24,608 outpatient visits per 100,000 people; and there were 9894 vs 2546 inpatient admissions per 100,000 people (all p < 0.001). The corresponding total costs of hospital-based care for complications were €919 vs €232 per person (p < 0.001), and 74.7% of costs were then directly attributed to diabetes (€687 per person). Regression analyses distributed the costs of days absent from work across diabetes complications per se, basic type 2 diabetes effect and unattributed causes. Diabetes complications amounted to €1317 per person in 2016, accounting for possible complex interactions (25% of total costs of days absent). Key drivers of costs were the macrovascular complications angina pectoris, heart failure and stroke; and the microvascular complications eye diseases, including retinopathy, kidney disease and neuropathy. Early mortality in working ages cost an additional €579 per person and medications used in risk-factor treatment amounted to €418 per person. CONCLUSIONS/INTERPRETATION: The economic burden of complications in type 2 diabetes is substantial. Costs of absence from work in this study were found to be greater than of hospital-based care, highlighting the need for considering treatment consequences in a societal perspective in research and policy. Graphical abstract.

Days absent from work as a result of complications associated with type 2 diabetes: Evidence from 20 years of linked national registry data in Sweden.

AIMS: To analyse days absent from work related to individual microvascular, macrovascular and other complications of type 2 diabetes (T2D) and to identify key drivers of absence. MATERIALS AND METHODS: National health and socio-economic individual-level data were analysed for the years 1997 to 2016 for people with T2D, and age-, sex- and residential region-matched controls (5:1) using linkage to Swedish national administrative registers, based on personal identity numbers. Regression analyses accounting for individual-level clustering and education were estimated to obtain days absent by individual complications. Alternative analyses, for example, workforce indicator and age subgroups, were explored for robustness and comparison purposes. RESULTS: A total of 413 000 people with T2D aged <66 years, comprising 4.9 million person-years, was included. The crude proportion with any absence was higher among those with T2D compared to controls (47% vs. 26%) in the index year, and the median (IQR) number of days was higher (223 [77;359] vs. 196 [59;352]) if any absence. Regression analyses showed that complications per se were a key driver of days absent: stroke (+102 days); end-stage renal disease (+70 days); severe vision loss (+56 days); and angina pectoris, heart failure, and osteoarthritis (+53 days each). The alternative analyses showed similar levels of days absent and age subgroups differed in expected directions. CONCLUSIONS: This study provides evidence of the persisting impact on productivity from complications that supports continued efforts to reduce risk factors in T2D. Future studies on burden of disease and economic evaluations of new therapies and disease management may use this new set of complication-specific estimates to improve understanding of the value of reducing complications.

Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials.

AIM: To investigate treatment satisfaction with semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, versus placebo/active comparators in the SUSTAIN clinical trial programme. METHODS: In SUSTAIN 2-5 and 7, the Diabetes Treatment Satisfaction Questionnaire was used to evaluate patient-perceived treatment satisfaction, hyperglycaemia and hypoglycaemia. Post hoc subgroup analyses were conducted to explore the effects of gastrointestinal adverse events (GI AEs), weight loss (≥5%) or achieving glycaemic (HbA1c < 7%) targets on treatment satisfaction. RESULTS: Overall treatment satisfaction increased from baseline to end of treatment with all treatments across trials. Improvements were significantly greater with semaglutide versus comparators/placebo in SUSTAIN 2-5 (all P < 0.05), and generally greater in patients who achieved versus did not achieve weight loss and glycaemic targets, often with greater improvements with semaglutide 1.0 mg versus comparator/placebo in both weight loss groups. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycaemic control. In SUSTAIN 7, changes in overall treatment satisfaction score were generally lower in patients with versus without GI AEs at week 16 (except dulaglutide 0.75 mg), but similar by week 40. Perceived hyperglycaemia was significantly reduced from baseline to end of treatment with semaglutide versus all comparators/placebo (all P < 0.05). No differences between treatments were observed for perceived hypoglycaemia. CONCLUSIONS: Semaglutide was associated with significantly greater (SUSTAIN 2-5) or similar (SUSTAIN 7) improvements in overall treatment satisfaction versus comparators/placebo. Improvements in overall treatment satisfaction were generally greater in patients achieving versus not achieving treatment targets. Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4), NCT02305381 (SUSTAIN 5) and NCT02648204 (SUSTAIN 7). EudraCT: 2012-004827-19 (SUSTAIN 2), 2012-004826-92 (SUSTAIN 3), 2013-004392-12 (SUSTAIN 4), 2013-004502-26 (SUSTAIN 5) and 2014-005375-91 (SUSTAIN 7).

Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study.

BACKGROUND: For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal-bolus insulin regimen is often recommended. We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes. METHODS: We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01191268. FINDINGS: Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (-1·64% [95% CI -1·78 to -1·50], -17·93 mmol/mol [-19·44 to -16·42]) and dulaglutide 0·75 mg (-1·59% [-1·73 to -1·45], -17·38 mmol/mol [-18·89 to -15·87]) than in those receiving glargine (-1·41% [-1·55 to -1·27], -15·41 mmol/mol [-16·92 to -13·90]). The adjusted mean difference versus glargine was -0·22% (95% CI -0·38 to -0·07, -2·40 mmol/mol [-4·15 to -0·77]; p=0·005) for dulaglutide 1·5 mg and -0·17% (-0·33 to -0·02, -1·86 mmol/mol [-3·61 to -0·22]; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting. INTERPRETATION: Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment. FUNDING: Eli Lilly and Company.

Efficacy and safety of dulaglutide in the treatment of type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the AWARD phase 3 clinical trial program.

Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of dulaglutide have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarize these results from the six completed AWARD studies. At the primary endpoint, in five of the six studies, once weekly dulaglutide 1.5 mg was superior to the active comparator [exenatide, insulin glargine (two studies), metformin, and sitagliptin], with a greater proportion of patients reaching glycated hemoglobin A1c (HbA1c) targets of <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol). Dulaglutide 1.5 mg was non-inferior to liraglutide in AWARD-6. Once weekly dulaglutide 0.75 mg was evaluated in five of these trials and demonstrated superiority to the active comparator in four of five AWARD studies (exenatide, glargine, metformin, and sitagliptin), and non-inferiority to glargine in the AWARD-2 study. Similar to other GLP-1 receptor agonists, treatment with dulaglutide was associated with weight loss or attenuation of weight gain and low rates of hypoglycaemia when used alone or with non-insulin-secretagogue therapy. The most frequently reported adverse events were gastrointestinal, including nausea, vomiting, and diarrhea. The incidence of dulaglutide antidrug antibody formation was 1-2.8% with rare injection site reactions. In conclusion, dulaglutide is an effective treatment for T2DM and has an acceptable tolerability and safety profile. Copyright © 2016 John Wiley & Sons, Ltd.

Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro: an AWARD-4 substudy.

AIM: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide-1 receptor agonist treatment with an insulin-only regimen. METHODS: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26 and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia and glucose variability. The primary objective was treatment comparison for percentage time spent with CGM glucose values in the 3.9-7.8 mmol/L range after 26 weeks. RESULTS: At week 26, mean CGM values decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3 and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in the 3.9-7.8 mmol/L range. Percentage time in the 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than for glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. The overall within-patient standard deviation (s.d.) was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences among the groups with regard to measures of normoglycaemia or near-normoglycaemia and for the overall within-patient s.d. Treatment with glargine was associated with greater increases in percentage time spent with glucose values ≤3.9 mmol/L, with statistically significant differences between the groups at 52 weeks (p < 0.05). CONCLUSIONS: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.

Estimating the impact of changes in HbA1c, body weight and insulin injection regimen on health related quality-of-life: a time trade off study.

BACKGROUND: There are limited data on the potential short-term benefits associated with reductions in HbA1c levels, and understanding any immediate improvements in health related quality-of-life (HRQoL) through better glycaemic control may help inform diabetes management decisions. This time-trade-off (TTO) study investigated the short-term impact on HRQoL associated with three different aspects of diabetes management; HbA1c change, body weight change, and the complexity of treatment regimen. METHODS: The study was designed in three stages: Stage 1) Qualitative telephone interviews with people with type 2 diabetes (T2D) in Denmark who had experienced a decrease in their HbA1c level. Stage 2) A validation survey with people with T2D in Denmark to obtain quantifiable knowledge on the short-term effects of a change in HbA1c levels. Stage 3) TTO survey using health states based on results from stage 2. Respondents were either adults with T2D (Sweden) or from the general public (UK and Denmark) and were separately asked to evaluate seven health states through an internet-based survey. RESULTS: Results from 4060 respondents were available for the TTO analysis (UK n = 1777; Denmark n = 1799, Sweden n = 484). 'Well-controlled diabetes' was associated with utilities of 0.85-0.91 and 'not well-controlled diabetes' with utilities of 0.71-0.80 in all countries. Difference in utilities per HbA1c percentage point was smallest in Sweden and largest in Denmark (between 0.025-0.034 per HbA1c percentage point respectively). The treatment management health state associated with the lowest disutility was the once-daily insulin regimen. The disutility associated with per kg of weight change ranged from 0.0041-0.0073. CONCLUSIONS: Changes in HbA1c levels, insulin regimen and body weight are all likely to affect HRQoL for patients with T2D. A change in HbA1c is likely to have a short-term impact in addition to the effect on the development of long term diabetes complications. A treatment which has a simple regimen with fewer injections, and/or the need for less planning, and that causes weight loss or less weight gain, compared with other treatments, will have a positive impact on HRQoL.

Evaluation of glucose control when a new strategy of increased carbohydrate supply is implemented during prolonged physical exercise in type 1 diabetes.

PURPOSE: In healthy individuals, high carbohydrate intake is recommended during prolonged exercise for maximum performance. In type 1 diabetes (T1D), this would alter the insulin requirements. The aim of the study was to evaluate the safety of high glucose supplementation during prolonged exercise and the glucose control when a novel strategy of increased carbohydrate supply was implemented during prolonged exercise in T1D. METHODS: Eight subjects with T1D participated in a sports camp including sessions of prolonged exercise and individualized feedback during three consecutive days. This was later followed by a 90 km cross-country skiing race. Large amounts of carbohydrates, 75 g/h, were supplied during exercise and the insulin requirements were registered. Glucose was measured before, during and after exercise aiming at euglycaemia, 4-8 mmol/L (72-144 mg/dL). During the race, continuous glucose monitoring (CGM) was used as an aspect of safety and to allow direct and individual adjustments. RESULTS: Compared to ordinary carbohydrate supply during exercise, the high carbohydrate supplementation resulted in significantly increased insulin doses to maintain euglycaemia. During the cross-country skiing race, the participants succeeded to reach mean target glucose levels; 6.5 ± 1.9 mmol/L (117 ± 34 mg/dL) and 5.7 ± 1.5 mmol/L (103 ± 27 mg/dL) at the start and finish of the race, respectively. Episodes of documented hypoglycemia (<4 mmol/L/72 mg/dL) were rare. CGM was used for adjustments. CONCLUSION: In this study, large carbohydrate supplementation in T1D individuals during prolonged aerobic exercise is safe and allows the subjects to maintain glycaemic control and indicates the feasibility of CGM under these conditions.

Automated Insulin Delivery for Pregnant Women With Type 1 Diabetes: Where Do We Stand?

Automated insulin delivery (AID) systems mimic an artificial pancreas via a predictive algorithm integrated with continuous glucose monitoring (CGM) and an insulin pump, thereby providing AID. Outside of pregnancy, AID has led to a paradigm shift in the management of people with type 1 diabetes (T1D), leading to improvements in glycemic control with lower risk for hypoglycemia and improved quality of life. As the use of AID in clinical practice is increasing, the number of women of reproductive age becoming pregnant while using AID is also expected to increase. The requirement for lower glucose targets than outside of pregnancy and for frequent adjustments of insulin doses during pregnancy may impact the effectiveness and safety of AID when using algorithms for non-pregnant populations with T1D. Currently, the CamAPS® FX is the only AID approved for use in pregnancy. A recent randomized controlled trial (RCT) with CamAPS® FX demonstrated a 10% increase in time in range in a pregnant population with T1D and a baseline glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (6.5%). Off-label use of AID not approved for pregnancy are currently also being evaluated in ongoing RCTs. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and provide an overview of the completed and ongoing RCTs evaluating AID in pregnancy. In addition, we discuss the advantages and challenges of the use of current AID in pregnancy and future directions for research.

Automated Insulin Delivery Systems in Pediatric Type 1 Diabetes: A Narrative Review.

This narrative review assesses the use of automated insulin delivery (AID) systems in managing persons with type 1 diabetes (PWD) in the pediatric population. It outlines current research, the differences between various AID systems currently on the market and the challenges faced, and discusses potential opportunities for further advancements within this field. Furthermore, the narrative review includes various expert opinions on how different AID systems can be used in the event of challenges with rapidly changing insulin requirements. These include examples, such as during illness with increased or decreased insulin requirements and during physical activity of different intensities or durations. Case descriptions give examples of scenarios with added user-initiated actions depending on the type of AID system used. The authors also discuss how another AID system could have been used in these situations.

Diabetic retinopathy among the elderly with type 2 diabetes: A Nationwide longitudinal registry study.

PURPOSE: To investigate the prevalence, incidence and risk factors of DR in elderly people living with type 2 diabetes. METHODS: Individuals >80 years, in the Swedish National Diabetes Register (NDR) between 2008 and 2017, were included. Prevalence and incidence were calculated and stratified by age. Estimates were assessed by longitudinal binary logistic regression models. RESULTS: One hundred forty-one thousand, one hundred fifty-eight individuals with type 2 diabetes were included, median age 83 years, 53.3% females and with a median HbA1c 52 mmol/mol. The DR prevalence was stable at 336.2 cases/1000 patients in 2008 (95% CI, 330.2-342.3), with no significant changes during the 10-year period. Crude DR incidence rate: 88.5 cases/1000 patient years (95% CI, 87.6-89.4). The incidence rate was lower at higher ages. The effect of age on incident DR varied by sex, with females having an increasingly higher risk than males from 83 years of age, OR 1.25 (1.11-1.42) at age 90 years. The risk of incident DR with longer diabetes duration increased more rapidly at worse glycaemic control. CONCLUSION: The growing population of elderly with type 2 diabetes shows a stable proportion of DR and proposes an increased need for DR screening and eye care. Established risk factors for DR, such as diabetes duration and level of glycaemic control, are also important in the elderly; however, age and sex should be considered.

Insulin Pump Therapy and Adverse Skin Reactions With Focus on Allergic Contact Dermatitis in Individuals Living With Diabetes Mellitus: A Systematic Review and Clinical-Based Update.

BACKGROUND: The use of insulin pumps (continuous subcutaneous insulin infusion [CSII]) in individuals living with type 1 diabetes (T1D) improves disease control. However, adverse skin reactions may hamper compliance. We aimed to assess the relationship of insulin pumps, particularly that of infusion set therapy, used in children and adults with T1D and dermatitis including allergic contact dermatitis (ACD). METHODS: A systematic search of PubMed, and EMBASE, of full-text studies reporting dermatitis in persons with diabetes using a CSII was conducted from 2020 to 2023. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at the Department of Occupational and Environmental Dermatology, Malmö, Sweden (YMDA) was also performed highlighting the diagnostic process. RESULTS: Among the 391 screened abstracts, 21 studies fulfilled the inclusion criteria. Seven studies included data on children only, four studies were on adults, and nine studies reported data on both children and adults. Participants were exposed to a broad range of pumps. Dermatitis was rarely specified. Up to 60% of those referred to a university hospital due to skin reactions possibly related to insulin pumps had an ACD. CONCLUSIONS: The review and our findings indicate that there is not sufficient focus on contact allergy in the primary toxicological evaluations of substances used also for insulin pump therapy products and that possible adverse skin reactions are not correctly followed up in the clinical setting.

Effects, Safety, and Treatment Experience of Advanced Hybrid Closed-Loop Systems in Clinical Practice Among Adults Living With Type 1 Diabetes.

BACKGROUND: There are few studies providing a more comprehensive picture of advanced hybrid closed-loop (AHCL) systems in clinical practice. The aim was to evaluate the effects of the AHCL systems, Tandem® t: slim X2™ with Control IQ™, and MiniMed™ 780G, on glucose control, safety, treatment satisfaction, and practical barriers for individuals with type 1 diabetes. METHOD: One hundred forty-two randomly selected adults with type 1 diabetes at six diabetes outpatient clinics in Sweden at any time treated with either the Tandem Control IQ (TCIQ) or the MiniMed 780G system were included. Glycated hemoglobin A1c (HbA1c) and glucose metrics were evaluated. Treatment satisfaction and practical barriers were examined via questionnaires. RESULTS: Mean age was 42 years, median follow-up was 1.7 years, 58 (40.8%) were females, 65% used the TCIQ system. Glycated hemoglobin A1c was reduced by 0.6% (6.8 mmol/mol; 95% confidence interval [CI] = 0.5-0.8% [5.3-8.2 mmol/mol]; P < .001), from 7.3% to 6.7% (57-50 mmol/mol). Time in range (TIR) increased with 14.5% from 57.0% to 71.5% (95% CI = 12.2%-16.9%; P < .001). Time below range (TBR) (<70 mg/dL, <3.9 mmol/L) decreased from 3.8% to 1.6% (P < .001). The standard deviation of glucose values was reduced from 61 to 51 mg/dL (3.4-2.9 mmol/L, P < .001) and the coefficient of variation from 35% to 33% (P < .001). Treatment satisfaction increased, score 14.8 on the Diabetes Treatment Satisfaction Questionnaire (DTSQ) (change version ranging from -18 to 18, P < .001). Four severe hypoglycemia events were detected and no cases of ketoacidosis. Skin problems were experienced by 32.4% of the study population. CONCLUSIONS: Advanced hybrid closed-loop systems improve glucose control with a reasonable safety profile and high treatment satisfaction. Skin problems are common adverse events.