Optimizing Duration of Usage of Insulin Infusion Sets: Impact of Mechanical Stress on Infusion Sites and Identifying Individuals With IIS Issues

Insulin infusion sets (IIS) are essential for insulin delivery with insulin pumps and automated insulin delivery (AID) systems. Like Achilles, a Trojan war hero in Greece, IIS remains the heel prone to failure in ever-stronger AID systems. ¹ A soothsayer predicted Achilles would die in childhood, so his mother dipped him into the river Stix, which purportedly offered powers of invulnerability. Because his mother held him by his ankle, the river’s water did not touch it. Despite multiple efforts toward improving IIS, manufacturers have yet to visit the river Stix.

People with diabetes (PwD) are annoyed by the replacement of most current IIS every 2 to 4 days. It represents insulin pump therapy’s major annual economic burden while generating additional plastic waste. The first IIS designed for 7-day wear (up to 7 days) is now available in the EU and U.S. markets. ²

Insulin infusion set failures arise from leaks, full or partial detachments, and full or partial blockages. Allergic reactions to the plastic material and the adhesive used to attach the catheter to the skin also play a significant role in specific individuals. Other infrequent sources have been proposed, such as reduced insulin absorption from the subcutaneous insulin depot and increased insulin degradation at the infusion site. ³

Besides rising glucose, some of today’s insulin pumps and AID systems have no direct warning for IIS failure beyond checking the IIS when hyperglycemia does not respond after failed correction boluses. This delays the correction of hyperglycemia. Furthermore, after replacing the cartridge and IIS, the pump wearer may be misled by their bolus calculator’s subsequent correction bolus recommendation. Automated insulin delivery systems do not yet recognize IIS problems, erroneously calculating that recent bolus and basal insulins were delivered and that the listed insulin on board is correct. Several insufficient correction boluses may follow.

Another major factor affecting IIS wear time is the mechanical stress on the cannula or needle below the skin. Other than steel IIS with a second adhesive at the line connection about 4 inches or 10 centimeters from the site, current IIS designs are adhered only by an adhesive at the infusion site. Any tugs, pulls, or drops on the tubing can directly affect the cannula or needle below. After placing a Teflon cannula or steel needle under the skin, mechanical motion or tugs on the catheter or pump drops induce micro- or mini-movements of the cannula or needle below the skin. This may delay wound healing or cause inflammation. With less inflammation around Teflon cannulas, the motion may create a space along the cannula for partial leakage of insulin to the surface, resulting in hyperglycemia.

The impact of motion on 30°-angled infusion lines is the most straightforward to detect. Insulin may be visible at the transparent window around the cannula entry point. These IIS are often associated with “pump bumps,” small red, raised bumps visible at the window above a cannula entry site after a couple of days of wear. Pump bumps can remain visible on the skin for days or weeks following set removal. Adequate anchoring of the tubing with tape or an adhesive reduces irritation, inflammation, and the appearance of pump bumps.

The widely recognized inter-patient variability in the duration of IIS wear time between specific IIS might be driven by their propensity to cannula motion or differences in how well the IIS is anchored. Individuals also differ in dermatological aspects, including differences in the skin microbiome. Fixation of the IIS may extend wear time and lessen intra-individual differences. Different IIS might respond differentially to motion stress, depending on details of how well an infusion set is fixed to the skin.

Insulin infusion set design and adhesive selection directly affect the duration of wear. Unfortunately, we could not find any systematic clinical evaluation of a specific IIS concerning its susceptibility to motion stress. In principle, this factor could be studied by anchoring the line with tape or adhesive during one session of a given IIS and not anchoring it during the other session. This would provide clear intra-individual information about the impact of mechanical stress under daily conditions and if the functional duration of use may be increased. Insurers may be interested in funding IIS research because of the high costs of IIS failure and diabetic keto acidosis (DKA).

There are multiple comparisons between different IISs submitted for FDA approval. New designs seeking approval often select the QuickSet as the comparator. Medtronic recently published data comparing its new IIS approved for 7-day use with the QuickSet.^2,4 Survival for 3- and 7-day wear for the new IIS was 96% and 80.5%, respectively, while survival of 3-day wear for the QuickSet was 78%. Is the QuickSet the best comparator?

Determining which variables affect the duration of use will help identify successful IIS designs and can also identify individuals needing intervention. The length and variability of IIS use and the continuous glucose monitor (CGM) glucose values in 4- or 6-hour segments before and after set changes are essential for evaluating IIS performance. Do glucose values rise with the length of service? How often is hyperglycemia involved in set changes? Which individuals have variability of duration and hyperglycemia as the predominant factors for changing their infusion set? Which individuals have an IIS practice or type that places them at a greater risk of hyperglycemia or ketoacidosis?

In summary, IIS failure remains a significant source of hyperglycemia and DKA, and studies remain insufficient. Extensive data comparisons of specific IIS would identify more successful designs. For individuals, onboard detection of hyperglycemia and variability in set use could identify those having IIS issues and those at higher risk. Training insulin pump wearers to anchor the IIS appropriately onto the infusion site or at a certain distance before the infusion site may minimize direct motion stresses on the cannula and increase the successful duration of wear. We need more research, improved insulin leakage technology, and software integration that evaluates an individual’s risk for IIS failure.