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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 pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C ≤8.5%, C-peptide0.6 nmol/L, ≥6 months pump use) were enrolled in a crossover euglycemic clamp pilot study comparing conventional Teflon angled IISs to an investigational extended-wear IIS. PK/PD data from 6 participants was obtained for 5 hours post-bolus. While PD data were unstable, PK profiles of insulin lispro (0.15 U/kg bolus) show statistically significant, progressive decreases from Day 0 to 7 for tmax (p0.001), t50%(early) (p0.002), t50%(late) (p0.001), and Mean Residence Time (p0.001). AUC0-300 declined by approximately 22% from Day 0 to 7 (n.s.). 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.

Background: Worldwide, ∼1 million people manage their type 1 diabetes with an insulin pump and a continuous subcutaneous insulin infusion (CSII) catheter. Patients routinely insert a new catheter every 2–3 days due to increasing variability of insulin absorption over time. Catheter insertion and maintenance damage capillaries, lymphatics, cells, and connective tissue leading to an acute inflammatory response. Methods: We compared an investigational CSII catheter (IC) and a commercial CSII catheter (CC) regarding insulin absorption pharmacokinetics (PK) and tissue inflammation. The two different catheter designs were implanted into the subcutaneous tissue of six swine for 5 days. Insulin boluses were given on days 1, 3, and 5 of wear-time to assess PK. Tissue around catheters was excised and stained to visualize inflammation and morphological changes of adjacent tissue. Results: Insulin absorption was better when infused through a CC with highest Cmax and fastest tmax values on day 5 of catheter wear-time. Both catheter types produced high intra- and intersubject day-to-day insulin absorption variability. The IC caused significantly more tissue disruption and lead to irregular changes in tissue morphology. Both catheter types were surrounded by a layer of inflammatory tissue that varied in composition, thickness, and density over time. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion. Conclusions: Insulin absorption variability could be attributed to the layer of inflammatory tissue, which may function as a mechanical barrier to insulin flow into adjacent vascular tissue. The impact of the acute inflammatory tissue response on insulin absorption has to be considered in future catheter designs. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion.

The management reporting and assessment of glycemic control lacks standardization. The use of different methods to measure the blood glucose concentration and to report the performance of insulin treatment yields major disparities and complicates the interpretation and comparison of clinical trials. We convened a meeting of 16 experts plus invited observers from industry to discuss and where possible reach consensus on the most appropriate methods to measure and monitor blood glucose in critically ill patients and on how glycemic control should be assessed and reported. Where consensus could not be reached, recommendations on further research and data needed to reach consensus in the future were suggested. Recognizing their clear conflict of interest, industry observers played no role in developing the consensus or recommendations from the meeting. Consensus recommendations were agreed for the measurement and reporting of glycemic control in clinical trials and for the measurement of blood glucose in clinical practice. Recommendations covered the following areas: How should we measure and report glucose control when intermittent blood glucose measurements are used? What are the appropriate performance standards for intermittent blood glucose monitors in the ICU? Continuous or automated intermittent glucose monitoring - methods and technology: can we use the same measures for assessment of glucose control with continuous and intermittent monitoring? What is acceptable performance for continuous glucose monitoring systems? If implemented, these recommendations have the potential to minimize the discrepancies in the conduct and reporting of clinical trials and to improve glucose control in clinical practice. Furthermore, to be fit for use, glucose meters and continuous monitoring systems must match their performance to fit the needs of patients and clinicians in the intensive care setting.

Objective: This study shows the potential of continuous glucose monitoring (CGM) for the detection of hypoglycemia in hospitalized patients. Research Design and Methods: A Medtronic Diabetes (Northridge, CA) CGMS® iPro™ continuous glucose recorder was inserted into the subcutaneous tissue of a hospitalized orthopedic surgery patient with type 1 diabetes the day after a moderate hypoglycemia event. The interstitial fluid glucose concentration was recorded every 5 min. Both the patient and the hospital staff were blinded to the CGM data. Bedside capillary blood glucose measurements were performed per hospital protocol. Results: The CGM recorded a repeat severe episode of hypoglycemia the next day. The hospital-defined threshold for hypoglycemia (70 mg/dL) was crossed 4.5 h prior to the patient being found unconscious by the nursing staff. Conclusion: Data from the CGMS iPro Recorder illustrate the potential benefit of using a real-time CGM in the hospital to detect hypoglycemia in a more timely fas...