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
