Implementation of fully closed-loop insulin delivery for inpatients with diabetes: Real-world outcomes.

AIMS: Fully closed-loop insulin delivery has been shown in clinical trials to be safe and improve glucose control compared with standard insulin therapy in the inpatient setting. We investigated the feasibility of implementing the approved CamAPS HX fully closed-loop system in a hospital setting. METHODS: This implementation project was conducted in a large teaching hospital in Cambridge, UK. Healthcare professional training was multimodal including face-to-face workshops, online learning modules and supported by standard operating procedures. Set-up and maintenance of closed-loop devices were undertaken by the inpatient diabetes team. Selection of suitable patients was multidisciplinary and prioritised those with more challenging diabetes management. Demographic and clinical data were collected from electronic health records and diabetes data management platforms. RESULTS: In the 12 months since the closed-loop system was implemented, 32 inpatients (mean ± SD age 61 ± 16 years, 8 females, 24 males) used closed-loop insulin delivery during their admission, across medical and surgical wards in the hospital with a total of 555 days of closed-loop glucose control (median [IQR]: 14 [6, 22] days per inpatient). The time spent in target glucose range 3.9-10.0 mmol/L was 53.3 ± 18.3%. Mean glucose was 10.7 ± 1.9 mmol/L with 46.0 ± 18.2% of time spent with glucose >10.0 mmol/L. Time spent with sensor glucose below 3.9 mmol/L was low (median [IQR]: 0.38 [0.00, 0.85]). There were no episodes of severe hypoglycaemia or diabetic ketoacidosis during closed-loop use. CONCLUSIONS: We have demonstrated that the fully closed-loop system can be safely and effectively implemented by a diabetes outreach team in complex medical and surgical inpatients with challenging glycaemic control.

Technology in the management of type 2 diabetes: Present status and future prospects.

The growing incidence of type 2 diabetes (T2D) is a significant health concern, representing 90% of diabetes cases worldwide. As the disease progresses, resultant insulin deficiency and hyperglycaemia necessitates insulin therapy in many cases. It has been recognized that a significant number of people who have a clinical requirement for insulin therapy, as well as their healthcare professionals, are reluctant to intensify treatment with insulin due to fear of hypoglycaemia, poor understanding of treatment regimens or lack of engagement, and are therefore at higher risk of developing complications from poor glycaemic control. Over the past decade, the rise of diabetes technologies, including dosing advisors, continuous glucose monitoring systems, insulin pumps and automated insulin delivery systems, has led to great improvements in the therapies available, particularly to those requiring insulin. Although the focus has largely been on delivering these therapies to the type 1 diabetes population, it is becoming increasingly recognized that people with T2D face similar challenges to achieve recommended glycaemic standards and also have the potential to benefit from these advances. In this review, we discuss diabetes technologies that are currently available for people with T2D and the evidence supporting their use, as well as future prospects. We conclude that there is a clinical need to extend the use of these technologies to the T2D population to curb the consequences of suboptimal disease management in this group.

Day-to-day variability of insulin requirements in the inpatient setting: Observations during fully closed-loop insulin delivery.

The aim of this study was to characterize the variability of exogenous insulin requirements during fully closed-loop insulin delivery in hospitalized patients with type 2 diabetes or new-onset hyperglycaemia, and to determine patient-related characteristics associated with higher variability of insulin requirements. We retrospectively analysed data from two fully closed-loop inpatient studies involving adults with type 2 diabetes or new-onset hyperglycaemia requiring insulin therapy. The coefficient of variation quantified day-to-day variability of exogenous insulin requirements during up to 15 days using fully automated closed-loop insulin delivery. Data from 535 days in 67 participants were analysed. The coefficient of variation of day-to-day exogenous insulin requirements was 30% ± 16%, and was higher between nights than between any daytime period (56% ± 29% overnight [11:00 pm to 4:59 am] compared with 41% ± 21% in the morning [5:00 am to 10:59 am], 39% ± 15% in the afternoon [11:00 am to 4:59 pm] and 45% ± 19% during the evening [5:00 pm to 10:59 pm]; all P < 0.01). There is high day-to-day variability of exogenous insulin requirements in inpatients, particularly overnight, and diabetes management approaches should account for this variability.

Hypoglycemia and Hyperglycemia According to Type of Diabetes: Observations During Fully Closed-Loop Insulin Delivery in Adults With Type 1 and Type 2 Diabetes.

BACKGROUND: CamAPS HX fully closed-loop (FCL) system, with no user input required at mealtimes, has been shown to be safe and effective in adults with type 1 and type 2 diabetes. We assessed whether time spent in hypoglycemia and hyperglycemia during FCL insulin delivery in adults varied by type of diabetes over the 24-hour period. METHODS: We retrospectively analyzed eight weeks of data from 52 participants (adults with type 1 diabetes and adults with insulin-treated type 2 diabetes) recruited to two single-center randomized controlled studies using FCL insulin delivery during unrestricted-living conditions. Key outcomes were time spent in hypoglycemia <70 mg/dL and marked hyperglycemia >300 mg/dL by type of diabetes. RESULTS: The median percentage of time spent in hypoglycemia <70 mg/dL over the 24-hour period was lower for those with type 2 diabetes than for those with type 1 diabetes (median [interquartile range (IQR)] 0.43% [0.20-0.77] vs 0.86%, [0.54-1.46]; mean difference 0.46 percentage points [95% CI 0.23-0.70]; P < .001). Median percentage time in marked hyperglycemia >300 mg/dL was lower for those with type 2 diabetes than for those with type 1 diabetes (median [IQR] 1.8% [0.6-3.5] vs 9.3% [6.9-11.8]; mean difference 7.8 percentage points [95% CI 5.5-10.0]; P < .001). CONCLUSIONS: Using the FCL system, hypoglycemia and marked hyperglycemia exposure were lower in type 2 diabetes than in type 1 diabetes.

Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial.

In adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol-1 (9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9-10.0 mmol l-1). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0-42.6 percentage points; P < 0.001). Time > 10.0 mmol l-1 was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, -35.2 percentage points; 95% CI, -42.8 to -27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l-1 versus 12.6 ± 3.0 mmol l-1, respectively; mean difference, -3.6 mmol l-1; 95% CI, -4.6 to -2.5 mmol l-1; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol-1 (7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol-1 (8.7% ± 1.2%); mean difference, -15 mmol mol-1; 95% CI, -11 to -20 mmol l-1 (mean difference, -1.4%; 95% CI, -1.0 to -1.8%); P < 0.001). Time < 3.9 mmol l-1 was similar between treatments (a median of 0.44% (interquartile range, 0.19-0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00-1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).

Hybrid Closed-loop to Manage Gastroparesis in People With Type 1 Diabetes: a Case Series.

BACKGROUND: Gastroparesis is associated with unpredictable gastric emptying and can lead to erratic glucose profiles and negative impacts on quality-of-life. Many people with gastroparesis are unable to meet glycemic targets and there is a need for new approaches for this population. Hybrid closed-loop systems improve glucose control and quality-of-life but evidence for their use in people with diabetic gastroparesis is limited. METHODS: We present a narrative review of the challenges associated with type 1 diabetes management for people with gastroparesis and present a case series of 7 people with type 1 diabetes and gastroparesis. We compare glycemic control before and during the first 12 months of hybrid closed-loop therapy. Data were analyzed using electronic patient records and glucose management platforms. We also discuss future advancements for closed-loop systems that may benefit this population. RESULTS: Five of 7 patients had data available for time in range before and during hybrid closed-loop therapy, and all had an improvement in percentage time in target glucose range, with the overall mean time in range increasing from 26.0% ± 15.7% to 58.4% ± 8.6% during HCL use, (P = .004). There were significant reductions in HbA1c (83 ± 9 mmol/mol to 71 ± 14 mmol/mol) and mean glucose from 13.0 ± 1.7 mmol/L (234 ± 31 mg/dL) to 10.0 ± 0.7 mmol/L (180 ± 13 mg/dL) with use of a hybrid closed-loop system. Importantly, this was achieved without an increase in time in hypoglycemia (P = .50). CONCLUSION: Hybrid closed-loop systems may represent a valuable approach to improve glycemic control for people with type 1 diabetes and gastroparesis. Prospective studies are required to confirm these findings.

Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial.

We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart ('closed-loop') with standard insulin therapy and a masked continuous glucose monitor ('control') in random order. The primary endpoint was time in target glucose range (5.6-10.0 mmol l-1). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6-10.0 mmol l-1; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0-22.2; P < 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l-1; P = 0.003). Time in hypoglycemia (<3.9 mmol l-1) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0-0.4%) versus 0.2 (0.0-0.9%); P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.

Distinctive profile of IsomiR expression and novel microRNAs in rat heart left ventricle.

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that negatively regulate target gene expression through mRNA cleavage or translational repression. There is mounting evidence that they play critical roles in heart disease. The expression of known miRNAs in the heart has been studied at length by microarray and quantitative PCR but it is becoming evident that microRNA isoforms (isomiRs) are potentially physiologically important. It is well known that left ventricular (patho)physiology is influenced by transmural heterogeneity of cardiomyocyte phenotype, and this likely reflects underlying heterogeneity of gene expression. Given the significant role of miRNAs in regulating gene expression, knowledge of how the miRNA profile varies across the ventricular wall will be crucial to better understand the mechanisms governing transmural physiological heterogeneity. To determinine miRNA/isomiR expression profiles in the rat heart we investigated tissue from different locations across the left ventricular wall using deep sequencing. We detected significant quantities of 145 known rat miRNAs and 68 potential novel orthologs of known miRNAs, in mature, mature* and isomiR formation. Many isomiRs were detected at a higher frequency than their canonical sequence in miRBase and have different predicted targets. The most common miR-133a isomiR was more effective at targeting a construct containing a sequence from the gelsolin gene than was canonical miR-133a, as determined by dual-fluorescence assay. We identified a novel rat miR-1 homolog from a second miR-1 gene; and a novel rat miRNA similar to miR-676. We also cloned and sequenced the rat miR-486 gene which is not in miRBase (v18). Signalling pathways predicted to be targeted by the most highly detected miRNAs include Ubiquitin-mediated Proteolysis, Mitogen-Activated Protein Kinase, Regulation of Actin Cytoskeleton, Wnt signalling, Calcium Signalling, Gap junctions and Arrhythmogenic Right Ventricular Cardiomyopathy. Most miRNAs are not expressed in a gradient across the ventricular wall, with exceptions including miR-10b, miR-21, miR-99b and miR-486.