Autoimmune destruction of pancreatic beta-cells results in absolute insulin deficiency, type 1 diabetes mellitus (T1DM). Insulin therapy is required for people with T1DM to achieve an optimal glycated haemoglobin (HbA1c or A1c) along with controlled dayto- day blood glucose (BG) levels. While a variety of insulin delivery systems are available, factors such as the complexity of dosage calculation based on activity, diet and BG, the effectiveness of insulin delivery, ease of product use and ‘human’ issues, may affect concordance with treatment (see Table 1).1,2 Using an insulin delivery system which suits the patient’s lifestyle and addresses issues of delivery reliability may improve concordance and ameliorate BG variability. Continuous subcutaneous insulin infusion (CSII) therapy has been shown to:
• ensure accurate insulin delivery leading to improved A1c;3
• eliminate the unpredicatable effects of intermediate or long-acting insulin;3
• reduce severe low BG episodes; and3
• facilitate easier delivery of bolus insulin.3
In addition, a CSII system allows the patient flexibility in diet and meal times – users can exercise without having to eat large amounts of carbohydrate as the system can alter insulin delivery via a temporary basal rate.3
In this interview, Stephen C Bain describes the technical aspects of the Cellnovo mobile-connected diabetes management system.
Can you tell us about the available technologies in diabetes management and the current unmet need?
As I have outlined in Table 1, concordance to therapy is dependent on a number of factors. For me, ease of use and reliability of dosage delivery are crucial. CSII pumps both deliver drug therapy and aid self-management, so patients using such technology should expect accurate and safe drug delivery and the facility to immediately identify when a problem has occurred. However, while many of the available durable and patch pumps have a programmable memory, safety lockout features and remote control functions,4 most ‘lock in’ this information, thus, by the time it is assessed by the patient and/or a clinician, much of its value and relevance is lost.
What makes the Cellnovo system different to other insulin delivery devices?It is different because it is the first mobile diabetes management system, providing intuitive operation, internet connectivity and real-time tracking. The system comprises three core parts:
• a slim insulin pump with in-built activity monitor, which wirelessly connects to the app-based touch-screen handset;
• an app-based touch-screen handset; this features an integral BG monitor and a mobile data connection; the handset automatically records insulin dose, exercise and BG while also allowing for storage of diet information; and
• a comprehensive and secure web-based clinical management tool.
The system was created to reduce adverse incidents through its safety features and its ability to capture real-time data for rapid analysis and intervention by the patient and/or clinician where necessary.
What safety features does the Cellnovo device have?
The system has a number of alarms which relate to insulin delivery, occlusion, cartridge expiry alarm and temperature risk; the latter alarm alerts the patient if the ambient temperature exceeds 37 °C for a period of time, (i.e., the threshold where insulin is known to start to break down and become less effective). Box 1 outlines all the safety and function features.
Could you describe the mechanism of action of the miniaturised pump and how it differs from other pumps?
Most standard insulin pumps are simply a battery-driven automated syringe. In other pumps, this type of system is commonly used and comprises a modified injection syringe/cartridge filled with rapid-acting insulin, which is placed inside the pump. The cartridge is then emptied by means of a plunger, which advances by rotating along a helical thread. Insulin is released at variable speeds through a catheter into a subcutaneous tissue.
The Cellnovo pump is different from these other types of pumps in that it comprises two elements: a durable component and a disposable component.
The disposable component (the insulin cartridge) contains:
• the micro-actuator;
• the micro-valving system;
• an occlusion sensor; and
• an individual identification (ID) chip.
Let me explain how these components work. In the micro-actuator, wax is heated, causing it to expand; this forces the piston to move, displacing a small amount of insulin from the pumping chamber, out of the insulin cartridge, through the infusion set and into the patient (see Figure 1). Over time, doses deliver insulin as quasi-continuous basal delivery or as a larger bolus dose. A basal rate of 1 unit/hour would consist of 0.05 unit doses – a dose occurs every three minutes (20 doses in 1 hour). For a bolus dose, a mix of 0.1 and 0.05 units is used, due to the relatively large number of doses that need to be delivered in a short period of time. The 0.1 unit doses are used predominantly and 0.05 unit doses are used at the end of delivery to ensure accuracy.
The temperature of the wax in a solid state is measured in order to determine the correct activation time for the heating phase of the actuation cycle. In simple terms, the colder the wax, the more energy is needed to elevate the temperature to its liquid transition temperature. After the wax is heated and the first dose is delivered, the wax will cool and contract, returning to its solid state and volume.
The size of the basal rate will determine when the next dose is required; for example, larger basal rates have more doses to deliver per hour so the period between delivery doses will be shorter. The next heating cycle will begin at this point, again taking a measurement of the relative temperature of the wax in order to determine the activation time. This pulsing provides better control of accuracy of delivery per dose compared to some other commercially available patch pumps due to the feedback mechanisms described later.5