In Vivo Study of the Inflammatory Tissue Response Surrounding a Novel Extended-Wear Kink-Resistant Insulin Infusion Set Prototype Compared With a Commercial Control Over Two Weeks of Wear Time.

BACKGROUND: Infusion set function remains the limiting factor of insulin pump therapy due to nonmetabolic complications. Here, we tested an investigational extended-wear infusion set prototype with a soft, angled, wire-reinforced cannula with three additional side holes, and compared failure mechanisms and tissue response with a commercial Teflon control. METHODS: A total of 48 Teflon and 48 prototype infusion sets were inserted subcutaneously every other day for 14 days in 12 swine and infused with dilute insulin. After two weeks, tissue around cannulas was excised, and occlusions, leaks, and kinks were determined. Tissue was processed and stained to assess the total area of inflammation (TAI) and the inflammatory layer thickness (ILT) around the cannulas. Data were analyzed using Fisher's exact, analysis of variance-general linear model, Kruskal-Wallis, and post hoc tests. RESULTS: On average, the TAI surrounding the investigational cannula was 52.6% smaller than around the commercial control. The ILT was 66.3% smaller around investigational cannulas. Kinks occurred in 2.1% (investigational) vs 32.4% (commercial) cannulas (P < .001). There was no difference in occlusion alarms and leaks onto skin. CONCLUSIONS: The data suggest that the infusion set prototype elicits less inflammation over an extended wear time and is resistant to kinking, compared with a commercial Teflon device. This is consistent with previously published data on the impact of cannula material/angle on the inflammatory tissue response. We highlight the following important aspects of infusion set design: (1) secure skin adhesion, (2) reliable cannula insertion, (3) automatic removal of the stylet, (4) cannula material/design that resists kinking, and (5) minimization of local tissue inflammation.

Progressive Acceleration of Insulin Exposure Over 7 Days of Infusion Set Wear.

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide <0.6 nmol/L, ≥6 months pump use) were enrolled in a crossover euglycemic clamp pilot study comparing conventional Teflon angled IISs with an investigational extended-wear IIS. PK/PD data from six participants were obtained for 5 h postbolus. Although PD data were unstable, PK profiles (pooled data from both groups) of insulin lispro (0.15 U/kg bolus) showed statistically significant progressive decreases from days 0 to 7 for tmax (P < 0.001), Cmax (P < 0.05), and mean residence time (P < 0.0001). Area under the insulin concentration curve (AUC0-300) declined by ∼24% from days 0 to 7 (P < 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030).

Feasibility study of a prototype extended-wear insulin infusion set in adults with type 1 diabetes.

AIM: To assess the feasibility of a prototype insulin infusion set (IIS) for extended wear in adults with type 1 diabetes. MATERIALS AND METHODS: The prototype Capillary Biomedical investigational extended-wear IIS (CBX IIS) incorporates a soft, flexible, reinforced kink-resistant angled nylon-derivative cannula with one distal and three proximal ports to optimize insulin delivery. Twenty adult participants with type 1 diabetes established on insulin pump therapy used the CBX IIS for two 7-day test periods while wearing a Dexcom G5 continuous glucose monitor. RESULTS: Participants were able to wear the CBX IIS for an average of 6.6 ± 1.4 days. Eighty-eight percent (36 of 41) of sets were worn for 7 days. No serious adverse events were reported. Five infusion sets failed prematurely because of: unresolvable hyperglycaemia (three); hyperglycaemia with elevated ketones (one); or infection (one). Median time in range (3.9-10.0 mmol/L) was 62% (54-76). Average glucose levels per day of infusion set wear showed a statistically significant increase over time (p < .001). CONCLUSIONS: Our preliminary observations confirm the tolerability of the prototype CBX IIS for extended wear, albeit with a deterioration in glucose control after the third day.

Vascular Glucose Sensor Symposium: Continuous Glucose Monitoring Systems (CGMS) for Hospitalized and Ambulatory Patients at Risk for Hyperglycemia, Hypoglycemia, and Glycemic Variability.

Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non-critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost.

Use of an Intravascular Fluorescent Continuous Glucose Sensor in ICU Patients.

BACKGROUND: Hyperglycemia and hypoglycemia are associated with adverse clinical outcomes in intensive care patients. In product development studies at 4 ICUs, the safety and performance of an intravascular continuous glucose monitoring (IV-CGM) system was evaluated in 70 postsurgical patients. METHODS: The GluCath System (GluMetrics, Inc) used a quenched chemical fluorescence mechanism to optically measure blood glucose when deployed via a radial artery catheter or directly into a peripheral vein. Periodic ultrasound assessed blood flow and thrombus formation. Patient glucose levels were managed according to the standard of care and existing protocols at each site. Reference blood samples were acquired hourly and compared against prospectively calibrated sensor results. RESULTS: In all, 63 arterial sensors and 9 venous sensors were deployed in 70 patients. Arterial sensors did not interfere with invasive blood pressure monitoring, sampling or other aspects of patient care. A majority of venous sensors (66%) exhibited thrombus on ultrasound. In all, 89.4% (1383/1547) of arterial and 72.2% (182/252) of venous measurements met ISO15197:2003 criteria (within 20%), and 72.7% (1124/1547) of arterial and 56.3% (142/252) of venous measurements met CLSI POCT 12-A3 criteria (within 12.5%). The aggregate mean absolute relative difference (MARD) between the sensors and the reference was 9.6% for arterial and 14.2% for venous sensors. CONCLUSIONS: The GluCath System exhibited acceptable accuracy when deployed in a radial artery for up to 48 hours in ICU patients after elective cardiac surgery. Accuracy of venous deployment was substantially lower with significant rates of intravascular thrombus observed using ultrasound.

Accuracy of Intra-arterial and Subcutaneous Continuous Glucose Monitoring in Postoperative Cardiac Surgery Patients in the ICU.

BACKGROUND: The GluCath® intra-arterial continuous glucose monitoring (IA-CGM) system uses a novel quenched chemical fluorescence sensing mechanism to optically measure blood glucose when deployed in the radial artery. The aim of this study was to compare the accuracy of the IA-CGM and the FreeStyle Navigator® subcutaneous continuous glucose monitoring (SC-CGM) system with standard care. METHODS: After admission to the intensive care unit (ICU), the IA-CGM was inserted via a 20 gauge radial arterial study catheter and the SC-CGM was placed at the abdominal wall of postoperative cardiac surgery patients with an expected ICU length of stay > 24 hours. Each device was calibrated according to manufacturer instructions. Glucose values of both CGM systems were blinded for the clinical staff. Reference blood glucose samples were collected from the study catheter every 1-2 hours for at least 24 hours and analyzed on a Radiometer ABL blood gas analyzer. RESULTS: The IA-CGM and SC-CGM sensors were successfully inserted in 8 subjects. Accuracy assessment was performed with 183 paired points: 85.8% of the IA-CGM measurements and 84.2% of the SC-CGM measurements met ISO 15197:2003 glucometer criteria (within 20%) across a 79-248 mg/dl (4.4-13.8 mmol/L) glucose range. Overall ± SD mean absolute relative difference was 12.3 ± 11.3% for IA-CGM and 11.1 ± 8.3% for SC-CGM (difference -1.2%, 95% CI -3.3 to 0.8; P = .24). CONCLUSIONS: The IA-CGM system directly measured arterial blood glucose and did not interfere with clinical care. However, accuracy was similar to that of the less invasive SC-CGM device.