A Pilot Study for the Systematic Evaluation of the Inflammatory Response to Commercially Available Insulin Infusion Catheters in Subcutaneous Adipose Tissue

Background:

Approximately one million patients worldwide manage their diabetes with an insulin pump. Insulin is continuously infused into the subcutaneous adipose tissue via a Continuous Subcutaneous Insulin Infusion (CSII) catheter using a basal/bolus pattern that can be adjusted by the patient according to meal times, mimicking the natural function of the pancreas. One major advantage of this form of therapy is the improvement of living quality. Compared to multiple daily insulin injections, the catheter has to be inserted only once every 2-3 days where it remains within the subcutaneous tissue. This is especially advantageous for children of young age.

Unfortunately, insulin absorption from the tissue surrounding a CSII catheter can be slow, variable, and unreliable. It is recommended to replace infusion sets and CSII catheters after 2 to 3 days of clinical use. After this time, blood glucose control becomes difficult for the patient because insulin absorption from the subcutaneous tissue into the blood stream and lymphatics becomes highly variable.

The underlying mechanisms for impaired insulin absorption are poorly understood and the knowledge of rotating the site of injection is based on user experience. Frequently changing the injection site can be tedious and moreover leads to scarring, while reusing the same injection site can lead to medical complications such as lipohypertrophy. In order to develop CSII catheters with an extended life-time up to 7 days, there is a need to better understand the inflammatory response caused by the introduction and maintenance of a CSII catheter into the subcutaneous adipose tissue. The clinical use of a 7-day CSII catheter with low pharmacokinetics (PK) variability will significantly improve blood glucose control, decrease the risk for hypoglycemia, increase compliance, and decrease cost. Since continuous glucose monitoring (CGM) devices are approved for 7-day wear time, the development of a CSII catheter with extended lifetime is also crucial for the development of single-port artificial pancreas (AP) systems where CSII and CGM are combined in one catheter, mimicking pancreatic function. Furthermore, the improvement of catheter longevity will reduce insertion sites and scars. This is especially important for children with a smaller body surface area.

The choice of one material over the other is largely based on the patient's personal preference, his or her endocrinologist's or diabetes educator's opinion and therapy costs. There is a trend in both the United States and Europe towards using Teflon sets (90 % and 75 %, respectively) but approximately 40 to 45 % of pump users in Germany use steel catheters. Compared to Teflon, steel catheters are easier to insert and are less prone to kinking, and can be worn by patients allergic to Teflon. Patients using steel catheters report better metabolic control, less variable insulin absorption and less unexplained hyperglycemia (Heinemann 2016; Reichert et al. 2013). However, especially during exercise, steel may cause discomfort and the softer and more flexible Teflon catheter is assumed to be more comfortable to wear. The wear-time of the CSII catheter considerably varies between patients (from 2 to 10 days), although recommendations for the optimal frequency of changing an insulin infusion set (2 days for steel and 3 days for Teflon) exist.