A considerable hurdle for achieving patient acceptance for daily usage of any AP system is that it requires carrying around a number of devices at all times. The reluctance of many patients is illustrated by the large number who are not willing to use a CGM system regularly in addition to their pump in daily life.26
If it became possible to reduce the number of skin perforations to one (i.e., single-port), this would reduce the barrier to practical usage of an AP system; however, this requires glucose sensing at the site of insulin delivery. Such an approach would therefore improve patient comfort and simplify diabetes care. Such single port systems are under development, mainly in Europe.
One of the key questions with this approach is whether infused insulin has an impact on measured glucose levels, e.g., does infused insulin induce a local drop in glucose levels that results in a difficult-to-predict deviation of the glucose levels measured in interstitial fluid? Data show that it is possible to use two needles inserted close to each other without interference.27
Clinical experiments conducted by the University of Graz showed that a single-port approach is also feasible and that there is no need for more than one needle for both functions, i.e., glucose monitoring and insulin delivery.28,29
By inserting a special indwelling catheter (i.e., a microperfusion or microdialysis probe) into SC adipose tissue of patients with diabetes and using the catheter for simultaneous insulin delivery and glucose sampling, glucose concentration observed at the tissue site of insulin delivery correlates well with that seen in plasma.
In the AP@home project, two different innovative approaches are being developed in parallel with the aim to have at least one functional single-port AP system at the end of the project:
- The first approach relies on a nanoporous, glucose stimuli-responsive material that changes its permeability for insulin with the patient’s glucose levels;
- The second approach uses an insulin infusion catheter with an integrated glucose sensor that is inserted through a single skin perforation.
One of the aims of developing two single-port AP systems in parallel is to maximize the chances of success of this approach in general. It is not easy to predict which of the two approaches will become available first and which one will work better. It is not clear if both approaches will progress during the course of the project to clinical validation.
The first approach proposed by the Swiss company Sensile Medical () in close cooperation with an institute of the University of Lausanne is based on a glucose-responsive membrane. The system consists of three modules (from the outlet to the inlet):
Single-port AP approach based on a glucose-responsive cannula.
- A glucose-responsive, composite, nanoporous needle inserted subcutaneously and capable of dynamically changing its porosity as a function of glucose concentration in the SC environment. The needle will be closed with a pressure valve that allows bolus insulin injection;
- A flow meter capable of dynamically measuring changes in permeability of the outlet using tiny amounts of insulin (50–500 nl);
- An off-the-shelf microliter pump developed by Sensile Medical that is capable of delivering precise amounts of insulin solution.
The insulin-solution flow dynamics will be measured by the flow meter and controlled by the glucose-responsive needle, whereas the overall amount of insulin infused in the body will be controlled precisely by the microliter pump. The glucose-responsive, composite nanoporous needle (developed by the University of Lausanne) consists of hollow fibers with nanopores that will be modified with a glucose-sensitive phenylboronic acid (PBA)-based hydrogel that can to change its volume in the presence of glucose.30–33
Promising formulations of PBA hydrogel with a specific affinity for glucose at physiological conditions have been published.34,35
The second approach, developed by the University of Graz, modifies an insulin infusion catheter to accommodate a continuous, off-the-shelf glucose sensor. Two sensor placement concepts are being pursued (
): one placement concept involves modification of the holding pad of an insulin infusion cannula to accommodate a continuous glucose sensor (ex vivo
sensor placement). The second placement concept involves integration of a continuous glucose sensor directly onto the shaft wall of an insulin infusion cannula (in vivo
sensor placement). Whether the sensor is best placed outside the body within the insulin pump or within the body on the insulin delivery catheter is unknown and needs further investigation and development. With the latter approach (within the body), it was shown in a proof-of-principle study that simultaneous insulin delivery and glucose sampling at a single-port AP is possible.28,29
Single-port AP approach based on an insulin cannula with integrated glucose sensor.
Within the first year of development of the two single-port approaches, both approaches have made good progress and the first clinical evaluations have been scheduled to begin.