We Need More Research and Better Designs for Insulin Infusion Sets

An insulin infusion set (IIS) is an indispensable conduit in insulin pump systems that transfers insulin from the reservoir to the subcutaneous tissue. Some form of IIS is required for all pumps, including patch pumps. Transfer of insulin across the skin occurs through a stainless steel needle or through a Teflon cannula once its steel needle has been removed during the insertion process. With their ease of insertion, steel needles are inserted manually while Teflon catheters can be inserted manually, with an auto-insertion device, or in some cases either.

An insulin pump delivers only rapid-acting insulin, so any failure of the IIS can become a critical health issue. At best, IIS failure increases health care costs, while at the worst it can lead to elevated HbA1c levels, diabetic ketoacidosis (DKA), or death. Even though IIS designs have improved and fewer adverse events occur today, pump plumbing (IIS) continues to retain many similarities to home plumbing in the era of galvanized pipes fraught with a variety of ways to fail.

When an IIS issue of unexplained hyperglycemia or occlusion arises, several factors may be involved, including the physical design of the IIS, material composition of the catheter, tendency for dislodgement, presence or absence of a safety anchor or anchoring tape, type of insulin, strength of the adhesive used to fix the set to the skin, and the lubricant used to coat the exterior of a Teflon or steel cannula. Any of these may impact glucose outcomes, duration of use, and comfort.

Variations in the manufacturing process over time can also impact IIS reliability. Small changes or adjustments in IIS materials or the manufacturing process will sometimes have a considerable impact on IIS properties in daily life. For example, the thickness of the Teflon wall of a cannula is directly related to its risk of kinking during insertion, while its comfort is inversely related to a lesser degree. Fixation of IIS systems to the skin with adhesive also has a major impact on glucose outcomes, yet this remains a relatively ignored area for clinical research.

IIS reliability seems to vary by user and set. In pump blogs and in clinic and support group discussions, many users report that they have experienced acute metabolic deteriorations with one IIS or another that vanish once they switch to a different one, particularly when switching from a Teflon IIS to steel. Although anecdotal reports have to be taken with care, the number and consistency of these reports suggest that the type of IIS an individual chooses has a real impact on glucose control.

Patient Experience and Data About IIS Failure

Despite their critical role in insulin delivery, the number of research studies on IIS remains relatively small even though IIS failure is not rare.¹ One research study compared 45 pump wearers’ standard infusion set (44 Teflon and 1 steel) worn over a 1-month period to the Accu-Chek FlexLink infusion set studied during its third month of use in the trial. Insertion devices were used by 80% of participants with their standard IIS and by 93% with the IIS (FlexLink) being tested. Set failure, defined as immediate or unexplained hyperglycemia within the next 6 hours that could not be corrected, occurred during 8.9% of insertions of the standard sets (45 of 507 insertions). On the FlexLink Plus, the initial failure rate fell to 3.2% (15 of 488 insertions). This study strongly suggests that infusion set design can reduce initial IIS failure rates and with further design modifications might eventually be able to reduce overall failure rates.²

Initial failures were surprisingly common and are usually associated with use of an auto-insertion device. They occurred on the standard set once every 22.5 days with 2 day wear, and once every 33.7 days with 3 day wear. Subsequent to these initial failures, an additional 8% of sets failed in both groups. Just over 40% of participants had to replace an infusion set early at least once during this 1-month study in each IIS test group. One participant experienced DKA and 6 had measurable levels of ketones with hyperglycemia during the 60 days of study.

During an extended wear study of QuickSet Teflon and Sure-T steel IISs for 7 days or until failure, Quick-Sets were found to have a 15% initial failure rate. After the end of 1 week, the failure rate for steel and Teflon gradually equaled out at 64% for each IIS. During the entire 77 weeks of wear, 30% of sets failed because of hyperglycemia following a failed correction dose, 13% were removed for pain, 10% were pulled out by accident, 10% had erythema and/or induration of >10 mm, 5% fell out because of loss of adhesion, and 4% were removed for infection.³

After 7 days, 36% of the infusion sets were still operating and 32.5% were used for a full week (25 out of the total 77 weeks) with no increase in hyperglycemia or daily insulin requirements. The main predictor for length of wear in this study was the individual subject. The ability to use an IIS for an extended period of time varies for people on pumps, although it is not clear whether early failure is innate to individuals, or may be influenced by better IIS training.

A poster presented at the ADA and the DTM 2013 documented significant, intermittent, and unexplained elevations in blood glucose levels in pump wearers.⁴ By chance, pressure sensors had been installed in the infusion lines and researchers at Becton Dickinson were able to connect elevated pressure levels within the infusion line prior to the glucose elevations. Because an occlusion alarm was never triggered and the hyperglycemia was able to be corrected over time, these episodes were described as “hidden occlusions” and may explain some instances of unexplained hyperglycemia. If confirmed in other studies, an IIS redesign may be required to correct this issue.

In unpublished data from the Actual Pump Practices Study by 2 of the authors and Timothy Bailey, MD, the presence of an occlusion alarm was significantly associated with higher average glucose levels in 364 pump users during an average of 73 days of wear (P < .0001).⁵ In the low glucose tertile with an average glucose of 144 mg/dl, the average number of occlusions was 1.36 occlusions a month, while the middle and high tertiles, with average glucoses of 181 and 227 mg/dl respectively, averaged over 3.1 occlusion alarms a month. Among 12 other variables studied, only the frequency of hypoglycemia was more strongly associated with the average glucose level.

Data from a recent survey in Germany confirmed that success of the IIS is highly relevant for daily success with pump therapy.⁶ The metabolic control of patients using steel IIS (7.7%) was not different from that of those using Teflon IIS (7.8%); however, a smaller number of patients observed unexplained increases in glycemia with steel IIS (in total 405: yes n = 210 [52%] versus no n = 195 [48%]) than with Teflon (535: yes n = 313 [59%] versus no 222 [41%]; P < .05 [chi-square test]).

In reviewing continuous glucose monitoring (CGM) records, those who wear pumps often do not have awareness or memory for likely IIS failures and often use terms that may signify IIS failure, like “scarring,” “site failure,” or “poor absorption.” Many pump wearers are unable to identify the frequency of IIS failure or the impact it has on their overall control. However annoying or dangerous at the time they occur, IIS failure events can be easily forgotten amid daily life events and be difficult to distinguish from possible absorbtion issues. However, a simple test trial with an alternate reliable IIS will usually resolve this uncertainty. Any delay in correcting unexplained hyperglycemia leads to frustration and has been identified as a common source for discontinuation of insulin pump therapy.¹

Differences in Usage of IIS Between Countries

In view of the differences between patients with respect to age, sex, BMI, physical activities, and insulin pump variations, a clear need for a variety of IIS types exists. However, many pump wearers remain on the same IIS that is shipped with their pump or that the diabetes nurse supplied during their introduction to insulin pump therapy.

Most IIS are manufactured by a single company in Denmark. There is a scarcity of published data about how many pump wearers in different countries use steel versus Teflon IIS, and about which brands or styles are used in various locations. Survey data suggest that steel sets are more commonly used in Germany (~40% of sets) and Europe (~25%) than in the United States (~10%), and this may correlate with the market share for various brands of insulin pumps used in different countries.⁶

Steel Versus Teflon

Prior to starting on an insulin pump, a person may believe that steel needles will be less comfortable or carry more risk during physical work or sports activities than Teflon. While it is understandable that having a thin sharp needle in the skin might impose such risk, it appears that this is not the case. Patients generally report that steel IIS are simpler and easier to insert and as comfortable as Teflon. Although an occasional user will switch from steel to Teflon due to issues with bleeding or occlusion, the majority of Teflon users who try a steel set stay with it. Steel IIS are also less expensive at about $8 per set in the United States compared to $12 per set for Teflon. In a 2004 report, consumables made up the largest annual expense for those wearing an insulin pump, and IIS costs made up 84.2% to 89.5% of the annual expense.⁷

Compared to steel IIS where an insertion device is not needed, auto-insertion devices are commonly used with Teflon IIS. Given the few individuals who have a real fear of needles or are unable to manually insert an IIS, the widespread use of these devices is puzzling. Do patients really prefer Teflon IIS for good reasons or is there a marketing or training issue here? Is this preference for auto-inserters the main factor that sways pump wearers to use Teflon more than steel? And why do many pump manufacturers prefer Teflon instead of steel IIS? Variations in which styles and brands of IIS are used in different countries may be driven by the marketing activities and market share of pump manufacturers. Commissions for pump sales representatives are often partially determined by the number of sales they produce for a particular IIS.

Although a “soft” cannula may be easier to promote to those on pumps, there may also be economic advantages for insulin pump companies that make Teflon IIS sets more attractive. This may not be a good argument for patients if significant health risks are associated with certain IIS or with the insertion device used to install them. For most dextrous individuals, manually inserting a steel IIS provides better control with elimination of kinking and a lower rate of insertion failure compared to use of an insertion device.

Length of use recommendations for IIS is generally 2 days for steel sets and 3 days for Teflon sets, although we are unable to find any data supporting these recommendations and at least one study found no difference.⁸ For example, a study of Tender and Comfort IIS (both Teflon and identical other than the name) found that glucose levels gradually rose with each day of use.⁹ As a result of the study, the authors recommended that this Teflon set that is inserted at about a 30 degree angle be used for only 2 days.

This angled set is designed and commonly used without the infusion line being anchored with tape, so any tug or movement of the infusion line is directly transferred to its Teflon cannula under the skin. In our experience, this can lead to skin irritation, redness, and on occasion leakage of insulin along the Teflon cannula back to the skin. When the infusion line is simply anchored with tape, these problems largely disappear, and the same set can be worn for extended periods of time.

Discussion and Summary

The lack of reliable data about IIS performance is not reassuring. We have outlined some areas where IIS issues should be addressed, such as whether significant clinical differences exist between steel and Teflon IIS, whether auto-insertion devices create increased health risks, and the need to improve adhesion of sets to the skin. We encourage analysis of databases on pump-related medical events to confirm the extent of IIS issues and identify characteristics of IIS that minimize unwanted outcomes. IIS manufacturers and insulin pump companies whose customers use them, and diabetes advocacy groups like the ADA, EASD, and AACE, would ideally fund surveys and studies to evaluate IIS performance. To ensure unbiased results, both the design and data analysis of surveys and studies should be evaluated and published by independent clinicians to guarantee a balanced and unbiased presentation of the data.

CGM records provide a convenient method to identify and correct individual IIS problems. These records could also be used to identify variations in failure rates among different IIS brands and styles, between steel and Teflon, and with the use of an auto-insertion device. Larger data studies with more data may be needed to determine if clinically relevant differences exist between particular varieties of steel or Teflon IIS. Manufacturers, who are required by law to monitor this, should be able to analyze the number of patient complaints received by their call centers that may relate to IIS failure.

In view of the impact that the IIS can have on the success of pump therapy, wearers should be encouraged to try various IIS during their introduction to pump therapy by both clinicians and pump manufactures. Given the potential saving in cost of product and user frustration, as well as potential reductions in complaint calls and unnecessary pump and IIS replacements, pump manufacturers and insurance companies may find it advantageous to cover the minimal cost for this essential training. It would also be important to promote safe and successful use of IIS via social networks and encourage relevant groups to place more attention on this topic to increase IIS reliability.

Regulatory agencies require glucose meters to meet performance standards. Why aren’t infusion sets that are much more directly related to health outcomes also required to meet such standards?

In summary, IIS failure has a major impact on glucose control and is not uncommon for many pump wearers. It deserves more attention. We believe that the selection between steel or Teflon IIS, the use of auto-insertion devices, and methods that reduce tugging and pulling between the infusion line and cannula have a larger impact on the glycemic success of insulin pump therapy than is widely recognized. Patients who experience episodes of unexplained hyperglycemia or poor absorption with rapid swings in glycemia or development of unexplained ketoacidosis should vary the type of IIS they use to determine whether such acute deteriorations are related to their infusion set. In critical situations, such as young children on small insulin doses or a pregnant woman who requires consistent insulin delivery, patients should be advised about the reliability of steel and certain Teflon IIS once these are properly anchored by design or with tape. Infusion sets and sites need to carefully monitored. The goal for anyone who wears a pump would be to have less than one IIS failure per month and preferably none. Given the considerable price of each IIS, the frequency and variety of failures, and the negative impact on glycemia, a major redesign of IIS and auto-insertion devices is needed.

This commentary will hopefully initiate an open discussion about the type of IIS that is used and its relevance for insulin pump therapy. We encourage clinical studies that systematically evaluate the impact of different IIS in patients with diabetes and prove or disprove our beliefs. It is important that both types of IIS remain on the market as we believe that steel IIS produce a clear clinical advantage for many pump wearers.