Assessment of the Impact of Subcutaneous Catheter Change on Glucose Control in Patients with Type 1 Diabetes Treated by Insulin Pump in Open- and Closed-Loop Modes.

Introduction: Most continuous subcutaneous insulin infusion (CSII) catheters (KT) are changed every 3 days. This study aims at evaluating whether KT changes impact glucose control while under open-loop (OL) or automated insulin delivery (AID) modes. Methods: We included patients with type 1 diabetes who used Tandem t:slim x2 insulin pump and Dexcom G6 glucose sensor for 20 days in OL, then as AID. CSII and sensor glucose data in OL and for the past 20 days of 3-month AID were retrospectively analyzed. The percentage of time spent with sensor glucose above 180 mg/dL (%TAR180) was compared between the calendar day of KT change (D0), the next day (D1), and 2 days later (D2). Values were adjusted for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c) at inclusion, and %TAR180 for the 2 h before KT change. Results: A total of 1636 KT changes were analyzed in 134 patients: 72 women (54%), age: 35.6 ± 15.7 years, BMI: 25.2 ± 4.7 kg/m2, and HbA1c: 7.5 ± 0.8%. %TAR180 in the 2 h before the KT change was 51.3 ± 37.0% in OL and 33.2 ± 30.0% in AID mode. In OL, significant absolute increases of %TAR180 at D0 versus D1 (+6.9%; P < 0.0001) or versus D2 (+6.8%; P < 0.0001) were observed. In AID, significant absolute increases of %TA180R at D0 versus D1 (+4.8%; P < 0.0001) or versus D2 (+4.2%; P < 0.0001) were also observed. Conclusion: This study shows an increase in time spent in hyperglycemia on the day of the KT change both in OL and AID modes. This additional information should be taken into account to improve current AID algorithms. ClinicalTrials.gov: NCT04939766.

New ex vivo method to objectively assess insulin spatial subcutaneous dispersion through time during pump basal-rate based administration.

Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.

Is the Consensual Threshold for Defining High Glucose Variability Implementable in Clinical Practice?

OBJECTIVE: Estimating glycemic variability (GV) through within-day coefficient of variation (%CVw) is recommended for patients with type 1 Diabetes (T1D). High GV (hGV) is defined as %CVw > 36%. However, continuous glucose monitoring (CGM) devices provide exclusively total CV (%CVT). We aimed to assess consequences of this disparity. RESEARCH DESIGN AND METHODS: We retrospectively calculated both %CVT and %CVw of consecutive T1D patients from their CGM raw data during 14 days. Patients with hGV with %CVT >36% and %CVw ≤36% were called the "inconsistent GV group". RESULTS: A total of 104 patients were included. Mean ± SD %CVT and %CVw were 42.4 ± 8% and 37.0 ± 7.4% respectively (P < 0.0001). Using %CVT, 81 patients (73.6%) were classified as having hGV, whereas 59 (53.6%) using %CVw (P < 0.0001) corresponding to 22 patients (21%) in the inconsistent GV population. CONCLUSIONS: Evaluation of GV through %CV in patients with T1D is highly dependent on the calculation method and then must be standardized.

All Insulin Pumps Are Not Equivalent: A Bench Test Assessment for Several Basal Rates.

Background and Aims: Continuous subcutaneous insulin infusion (CSII) is a widely adopted treatment for type 1 diabetes and is a component of an artificial pancreas. CSII accuracy is essential for glycemic control, however, this metric has not been given sufficient study, especially at the range of the lowest basal rates (BRs), which are commonly used in a pediatric population and in closed-loop systems (CLSs). Our study presents accuracy results of four off-the-shelf CSII systems using a new accurate method for CSII system evaluation. Materials and Methods: The accuracy of four off-the-shelf CSII systems was assessed: Medtronic MiniMed 640G®, Ypsomed YpsoPump®, Insulet Omnipod®, and Tandem t:slim X2®. The assessment was performed using a double-measurement approach through a direct mass flow meter and a time-stamped microgravimetric test bench combined with a Kalman mathematical filter. CSII accuracy was evaluated using mean of dose error. Mean absolute relative difference (MARD) of error was calculated at different observation windows over the whole series of tests. Peakwise insulin deliverance was assessed regarding stroke regularity in terms of frequency and volume. Results: Mean error values indicate a general tendency to underdeliver with up to -16%. MARD of error shows very wide results for each pump and each BR from 7.4% (2 UI/h) to 61.3% (0.1 UI/h). Peakwise analysis shows several choices for BR adaptation (frequency for Omnipod, volume for Tandem, both for YpsoPump and MiniMed 640G). Precision in interstroke time appears to be better (standard deviation [SD] at 0.1 UI/h: 4.6%-12.9%) than stroke volume precision (SD at 0.1 UI/h 38.3%-46.4%). Conclusions: The accuracy of four off-the-shelf CSII systems is model and BR dependent. CSII imprecision could be due to a variability in volume and/or frequency of strokes for every pump. Some models appear better adapted for the smallest insulin needs, or for inclusion in a CLS. The clinical implications of these delivery errors on glucose instability must be evaluated.

Kalman Filter-Based Novel Methodology to Assess Insulin Pump Accuracy.

Background: Insulin pump or continuous subcutaneous insulin infusion (CSII) system is a widely adopted contemporary treatment for type 1 diabetes and is a major component of an artificial pancreas (AP). CSII accuracy is essential for glycemic control and to-date such metric has not been given sufficient study, especially at the range of the lowest basal rate. The gold-standard assessment method IEC (International Electrotechnical Commission) 60601-2-24 has some limitations. Our study presents a new accurate and reactive method for CSII system evaluation based on direct flow measurement. Materials and Methods: A leading-edge assessment method based on a double measurement approach utilizing a direct mass flow meter and a time-stamped microgravimetric bench test was combined with a Bayesian-based mathematical filter (Kalman). The performance of this new method was evaluated while assessing the delivery precision of an off-the-shelf insulin pump at several basal rates. The proposed methodology offers a double reading-volume and flow rate-which provides direct instantaneous flow rate. CSII dose errors were evaluated using mean absolute relative dispersion (MARD) at different time intervals windows over the whole test. Results: The metrological aspect of the measurements and filtering performance were consistent. CSII precision is shown to be different in terms of the flow rate value: MARD15min (2 UI/h) = 12.7%, MARD15min (0.5 UI/h) = 20.4%, and MARD15min (0.1 UI/h) = 65.0%. MARD240min (2 UI/h) = 8.1%, (0.5 UI/h), MARD240min (0.5 UI/h) = 18.8%, and MARD240min (0.1 UI/h) = 18.4%. Instantaneous flow rate results highlight an irregular stroke-based delivery. Conclusion: This new method to assess insulin pump administration has been validated and highlights the current imprecision in insulin delivery, especially for the lowest basal rate, which is mainly used in pediatric cases and AP system delivery. This leading-edge method should be used to precisely compare several CSII performances in those contexts.