Technology in the management of diabetes in hospitalised adults.

Suboptimal glycaemic management in hospitals has been associated with adverse clinical outcomes and increased financial costs to healthcare systems. Despite the availability of guidelines for inpatient glycaemic management, implementation remains challenging because of the increasing workload of clinical staff and rising prevalence of diabetes. The development of novel and innovative technologies that support the clinical workflow and address the unmet need for effective and safe inpatient diabetes care delivery is still needed. There is robust evidence that the use of diabetes technology such as continuous glucose monitoring and closed-loop insulin delivery can improve glycaemic management in outpatient settings; however, relatively little is known of its potential benefits and application in inpatient diabetes management. Emerging data from clinical studies show that diabetes technologies such as integrated clinical decision support systems can potentially mediate safer and more efficient inpatient diabetes care, while continuous glucose sensors and closed-loop systems show early promise in improving inpatient glycaemic management. This review aims to provide an overview of current evidence related to diabetes technology use in non-critical care adult inpatient settings. We highlight existing barriers that may hinder or delay implementation, as well as strategies and opportunities to facilitate the clinical readiness of inpatient diabetes technology in the future.

What Is the Tech Missing? Nutrition Reporting in Type 1 Diabetes.

INTRODUCTION: Type 1 Diabetes (T1D) presents self-management challenges, requiring an additional 180 daily decisions to regulate blood glucose (BG) levels. Despite the potential, T1D-focused applications have a 43% attrition rate. This work delves into the willingness of people living with T1D (PwT1D) to use technology. METHOD: An online questionnaire investigated the current practices for carbohydrate estimation, nutritional tracking, and attitudes towards technology engagement, along with hypothetical scenarios and preferences regarding technology use. RESULTS: Thirty-nine responses were collected from PwT1D (n = 33) and caregivers (n = 6). Nutrition reporting preferences varied, with 50% favoring 'type and scroll' while 30% preferred meal photographing. Concerning the timing of reporting, 33% reported before meals, 55% after, and 12% at a later time. Improved Time in Range (TIR) was a strong motivator for app use, with 78% expressing readiness to adjust insulin doses based on app suggestions for optimizing TIR. Meal descriptions varied; a single word was used in 42% of cases, 23% used a simple description (i.e., "Sunday dinner"), 30% included portion sizes, and 8% provided full recipes. CONCLUSION: PwT1D shows interest in using technology to reduce the diabetes burden when it leads to an improved TIR. For such technology to be ecologically valid, it needs to strike a balance between requiring minimal user input and providing significant data, such as meal tags, to ensure accurate blood glucose management without overwhelming users with reporting tasks.

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

Intermittently scanned continuous glucose monitoring in adults with type 1 diabetes: A subgroup analysis from the FLASH-UK study.

AIMS: The FLASH-UK trial showed lower HbA1c with intermittently scanned continuous glucose monitoring (isCGM), as compared with self monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol (≥7.5%). Here, we present results from the pre-specified subgroup analysis for the 24-week HbA1c (primary outcome) and selected sensor-based secondary outcomes. METHODS: This was a multi-centre, parallel-design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c [≤75 vs. >75 mmol/mol] [≤9.0 vs >9.0%], treatment modality [pump vs injections], prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group and Patient Health Questionnaire-9 [PHQ-9] detected depression category) were evaluated. RESULTS: One hundred fifty-six participants (females 44%, mean [SD] baseline HbA1c 71 [9] mmol/mol 8.6 [0.8%], age 44 [15]) were randomly assigned, in a 1:1 ratio to isCGM (n = 78) or SMBG (n = 78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) versus 8.3 (0.9), respectively, at 24 weeks (adjusted mean difference -0.5, 95% confidence interval [CI] -0.7 to -0.3; p < 0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between-group difference in HbA1c was larger for younger people (a reduction of 2.7 [95% CI 0.3-5.0; p = 0.028] mmol/mol for every additional 15 years of age). Those with HbA1c 76-97 mmol/mol (>9.0%-11.0%) had a marginally non-significant higher reduction in HbA1c of 8.4 mmol/mol (3.3-13.5) compared to 3.1 (0.3-6.0) in those with HbA1c 58-75 mmol/mol (p = 0.08). For 'Time in range' (% 3.9-10 mmol/L), the difference was larger for those with at least a bachelor's degree. For 'Time below range' (% <3.9 mmol/L), the difference was larger for those using injections, older people and those with less than bachelor's degree. CONCLUSIONS: Intermittently scanned continuous glucose monitoring is generally effective across a range of baseline characteristics.

Estimating the cost-effectiveness of intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in England.

OBJECTIVE: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self-monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58-97 mmol/mol [7.5%-11%]). We aim to assess the economic impact of isCGM compared with SMBG. METHODS: Participant-level baseline and follow-up health status (EQ-5D-5L) and within-trial healthcare resource-use data were collected. Quality-adjusted life-years (QALYs) were derived at 24 weeks, adjusting for baseline EQ-5D-5L. Participant-level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%. RESULTS: Within-trial EQ-5D-5L showed non-significant adjusted incremental QALY gain of 0.006 (95% CI: -0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of £548 (95% CI: 381-714) per participant. The lifetime projected incremental cost (95% CI) of isCGM was £1954 (-5108 to 8904) with an incremental QALY (95% CI) gain of 0.436 (0.195-0.652) resulting in an incremental cost-per-QALY of £4477. In all subgroups, isCGM had an incremental cost-per-QALY better than £20,000 compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost-saving. Sensitivity analysis suggested that isCGM remains cost-effective if its effectiveness lasts for at least 7 years. CONCLUSION: While isCGM is associated with increased short-term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long-term health-gains and cost-savings to justify costs, so long as the effect lasts into the medium term.

Time Spent in Hypoglycemia According to Age and Time of Day: Observations During Closed-Loop Insulin Delivery.

Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia <3.9 mmol/L (<70 mg/dL). Eight weeks of data for 88 participants were analyzed. Results: Median time spent in hypoglycemia over the 24-h period was highest in children and adolescents (4.4% [interquartile range 2.4-5.0]) and very young children (4.0% [3.4-5.2]), followed by adults (2.7% [1.7-4.0]), and older adults (1.8% [1.2-2.2]); P < 0.001 for difference between age groups. Time spent in hypoglycemia during nighttime (midnight-05:59) was lower than during daytime (06:00-23:59) across all age groups. Conclusion: Time in hypoglycemia was highest in the pediatric age group during closed-loop insulin delivery. Hypoglycemia burden was lowest overnight across all age groups.

Pancreas transplantation today: quo vadis?

Successful pancreas or islet transplantation is currently the only cure for type 1 diabetes mellitus. Since the first pancreas transplant in 1966, there have been various refinements of surgical technique along with improved immunosuppressive regimens, resulting in significantly improved outcomes, with contemporary research into graft monitoring and newer biomarkers, potentially lengthening graft survival rates further. Patients with insulin-dependent diabetes mellitus who are eligible for pancreas or islet transplantation represent a select group, the tip of the iceberg for a significant global diabetes disease burden. In the last 50 years, there have been quantum advances in alternative technologies in diabetes therapy, both experimental and translational. Further development and improved access are required to treat the larger proportion of people suffering from diabetes. Emerging stem cell therapy is still experimental whereas alternatives including automated insulin delivery systems and islet cell transplantation are already used in some countries. Whilst automated insulin delivery systems have increased in efficacy, they still do not achieve the near physiological control of blood sugar, which can be achieved by successful pancreas or islet transplantation. This state-of-the-art review provides a summary of pancreas and islet transplantation to its current place in diabetes therapy, along with alternative and future therapies, including the obstacles associated with the dissemination of these new therapies. With the advent of these modern cellular and technological advances, this review addresses the question: are we entering an era where whole organ pancreas transplantation could be replaced entirely by modern technological advances in diabetes therapy?

Analysis of "Accuracy of a Seventh-Generation Continuous Glucose Monitoring System in Children and Adolescents With Type 1 Diabetes".

In an article in the Journal of Diabetes Science and Technology, Laffell et al examined the accuracy and performance of a seventh-generation "G7" continuous glucose monitor (CGM) system in participants with type 1 diabetes aged 2 to 17 years. The study had notable points which increase the generalizability of the authors' findings to usual clinical practice, such as accuracy assessment across a wide range of glycemia in the arm and abdominal area, at variable rates of change and time periods (beginning and end of sensor wear). However, accuracy measurements in the younger cohort (2-6 years old) were relatively few. Overall and per-sensor accuracy assessments using standard accuracy metrics were consistently high. The authors also highlighted the enhanced features of the G7 system compared to earlier generation systems, which support better usability.

Safety of User-Initiated Intensification of Insulin Delivery Using Cambridge Hybrid Closed-Loop Algorithm.

OBJECTIVE: Many hybrid closed-loop (HCL) systems struggle to manage unusually high glucose levels as experienced with intercurrent illness or pre-menstrually. Manual correction boluses may be needed, increasing hypoglycemia risk with overcorrection. The Cambridge HCL system includes a user-initiated algorithm intensification mode ("Boost"), activation of which increases automated insulin delivery by approximately 35%, while remaining glucose-responsive. In this analysis, we assessed the safety of "Boost" mode. METHODS: We retrospectively analyzed data from closed-loop studies involving young children (1-7 years, n = 24), children and adolescents (10-17 years, n = 19), adults (≥24 years, n = 13), and older adults (≥60 years, n = 20) with type 1 diabetes. Outcomes were calculated per participant for days with ≥30 minutes of "Boost" use versus days with no "Boost" use. Participants with <10 "Boost" days were excluded. The main outcome was time spent in hypoglycemia <70 and <54 mg/dL. RESULTS: Eight weeks of data for 76 participants were analyzed. There was no difference in time spent <70 and <54 mg/dL between "Boost" days and "non-Boost" days; mean difference: -0.10% (95% confidence interval [CI] -0.28 to 0.07; P = .249) time <70 mg/dL, and 0.03 (-0.04 to 0.09; P = .416) time < 54 mg/dL. Time in significant hyperglycemia >300 mg/dL was 1.39 percentage points (1.01 to 1.77; P < .001) higher on "Boost" days, with higher mean glucose and lower time in target range (P < .001). CONCLUSIONS: Use of an algorithm intensification mode in HCL therapy is safe across all age groups with type 1 diabetes. The higher time in hyperglycemia observed on "Boost" days suggests that users are more likely to use algorithm intensification on days with extreme hyperglycemic excursions.

Evaluating the Impact of Applying Personal Glucose Targets in a Closed-Loop System for People With Type 1 Diabetes.

BACKGROUND: CamAPS FX is a hybrid closed-loop smartphone app used to manage type one diabetes. The closed-loop algorithm has a default target glucose of 5.8 mmol/L (104.5 mg/dL), but users can select personal glucose targets (adjustable between 4.4 mmol/L and 11.0 mmol/L [79 mg/dL and 198 mg/dL, respectively]). METHOD: In this post-hoc analysis, we evaluated the impact of personal glucose targets on glycemic control using data from participants in five randomized controlled trials. RESULTS: Personal glucose targets were widely used, with 20.3% of all days in the data set having a target outside the default target bin (5.5-6.0 mmol/L [99-108 mg/dL]). Personal glucose targets >6.5 mmol/L (117 mg/dL) were associated with significantly less time in target range (3.9-10.0 mmol/L [70-180 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: mean difference = -3.2 percentage points [95% CI: -5.3 to -1.2; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -10.8 percentage points [95% CI: -14.1 to -7.6; P < .001]). Personal targets >6.5 mmol/L (117 mg/dL) were associated with significantly lower time (<3.9 mmol/L [<70 mg/dL]; 6.5-7.0 mmol/L [117-126 mg/dL]: -1.85 percentage points [95% CI: -2.37 to -1.34; P < .001]; 7.0-7.5 mmol/L [126-135 mg/dL]: -2.68 percentage points [95% CI: -3.49 to -1.86; P < .001]). CONCLUSIONS: Discrete study populations showed differences in glucose control when applying similar personal targets.

Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes.

BACKGROUND: In persons with type 1 diabetes and high glycated hemoglobin levels, the benefits of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels are uncertain. METHODS: In a parallel-group, multicenter, randomized, controlled trial involving participants with type 1 diabetes and glycated hemoglobin levels between 7.5% and 11.0%, we investigated the efficacy of intermittently scanned continuous glucose monitoring as compared with participant monitoring of blood glucose levels with fingerstick testing. The primary outcome was the glycated hemoglobin level at 24 weeks, analyzed according to the intention-to-treat principle. Key secondary outcomes included sensor data, participant-reported outcome measures, and safety. RESULTS: A total of 156 participants were randomly assigned, in a 1:1 ratio, to undergo intermittently scanned continuous glucose monitoring (the intervention group, 78 participants) or to monitor their own blood glucose levels with fingerstick testing (the usual-care group, 78 participants). At baseline, the mean (±SD) age of the participants was 44±15 years, and the mean duration of diabetes was 21±13 years; 44% of the participants were women. The mean baseline glycated hemoglobin level was 8.7±0.9% in the intervention group and 8.5±0.8% in the usual-care group; these levels decreased to 7.9±0.8% and 8.3±0.9%, respectively, at 24 weeks (adjusted mean between-group difference, -0.5 percentage points; 95% confidence interval [CI], -0.7 to -0.3; P<0.001). The time per day that the glucose level was in the target range was 9.0 percentage points (95% CI, 4.7 to 13.3) higher or 130 minutes (95% CI, 68 to 192) longer in the intervention group than in the usual-care group, and the time spent in a hypoglycemic state (blood glucose level, <70 mg per deciliter [<3.9 mmol per liter]) was 3.0 percentage points (95% CI, 1.4 to 4.5) lower or 43 minutes (95% CI, 20 to 65) shorter in the intervention group. Two participants in the usual-care group had an episode of severe hypoglycemia, and 1 participant in the intervention group had a skin reaction to the sensor. CONCLUSIONS: Among participants with type 1 diabetes and high glycated hemoglobin levels, the use of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels resulted in significantly lower glycated hemoglobin levels than levels monitored by fingerstick testing. (Funded by Diabetes UK and others; FLASH-UK ClinicalTrials.gov number, NCT03815006.).

Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study.

Background: Older adults with type 1 diabetes have distinct characteristics that can make optimising glycaemic control challenging. We sought to test our hypothesis that hybrid closed-loop glucose control is safe and more effective than sensor-augmented pump (SAP) therapy in older adults with type 1 diabetes. Methods: In an open-label, multicentre, multinational (UK and Austria), randomised, crossover study, adults aged 60 years and older with type 1 diabetes using insulin pump therapy underwent two 16-week periods comparing hybrid closed-loop (CamAPS FX, CamDiab, Cambridge, UK) and SAP therapy in random order. Block randomisation by means of central randomisation software to one of two treatment sequences was stratified by centre. The primary endpoint was the proportion of time sensor glucose was in target range between 3·9 and 10·0 mmol/L. Analysis for the primary endpoint and adverse events was by intention-to-treat. The study has completed and is registered at ClinicalTrials.gov NCT04025762. Findings: 38 participants were enrolled. One participant withdrew during run-in because of difficulties with the study pump infusion sets. 37 participants (median [IQR] age 68 [63-70] years, mean [SD] baseline glycated haemoglobin [HbA1c]; 7·4% [0·9%]; 57 [10] mmol/mol) were randomly assigned between Sept 4, 2019, and Oct 2, 2020. The proportion of time with glucose between 3·9 and 10·0 mmol/L was significantly higher in the closed-loop group compared to the SAP group (79·9% [SD 7·9] vs 71·4% [13·2], difference 8·6 percentage points [95% CI 6·3 to 11·0]; p<0·0001). Two severe hypoglycaemia events occurred during the SAP period. There were two non-treatment related serious adverse events: cardiac arrest from pulmonary embolism associated with COVID-19 during the SAP period resulting in death, and a hospital presentation for parenteral hydrocortisone because of COVID-19 in a participant with adrenal insufficiency during the run-in period. Interpretation: Hybrid closed-loop insulin delivery is safe and achieves superior glycaemic control to SAP therapy in older adults with long duration of type 1 diabetes. Importantly this was achieved without increasing the risk of hypoglycaemia in this population with risk factors for severe hypoglycaemia. This suggests that hybrid closed-loop therapy is a clinically important treatment option for older adults with type 1 diabetes.

Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes.

OBJECTIVE: To assess associations between current use of sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effects meta-analysis. RESULTS: Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64). CONCLUSIONS: SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination.