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.
In a prior pig study the inflammatory response to commercial CSII catheters comparing steel,
Teflon and Teflon with an anti-inflammatory coating was analyzed. There was significant
reduction in area of inflammation and macrophage recruitment around the non-coated and coated
Teflon catheters. Steel elicited the most severe inflammatory response with significantly
higher fibrosis.
Although the pig has proven to be an excellent model for the study of human skin and adipose
tissue, there is an urgent medical need to confirm these findings in a human model. For the
histopathological and molecular analysis of subcutaneous tissue in the vicinity of the
catheter, large amounts of tissue need to be excised from the site of interest. This makes a
human study almost impossible. Nevertheless, the generation of human data is crucial and a
lot of this important information is still lacking in diabetes research and treatment. The
possibility to excise extensive amounts of tissue without causing additional scars or pain
(except that caused by the abdominoplasty itself) for the patient presents the main benefit
of this study setup.
Aim:
The aim of this study is to compare the inflammatory response to commercially available CSII
catheters of two different materials (steel and Teflon) over 1 day, 4 days and 7 days of
wear-time in humans scheduled for elective plastic surgery (abdominoplasty).
Hypothesis:
Conventional steel CSII catheters elicit a more severe acute inflammatory response in the
subcutaneous adipose tissue than Teflon CSII catheters.
H0 = there is no difference in mean area of fibrin deposition around catheters H1 = there is
a significant difference in mean area of fibrin deposition between catheters