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Diabetes Technol Ther. 2017 Nov;19(11):641-650. doi: 10.1089/dia.2017.0175. Epub 2017 Oct 5.

Detailed Analysis of Insulin Absorption Variability and the Tissue Response to Continuous Subcutaneous Insulin Infusion Catheter Implantation in Swine.

Author information

1
1 Department of Anesthesiology, Jefferson Artificial Pancreas Center, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.
2
2 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz , Graz, Austria .
3
3 Department of Pathology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.
4
4 Animas Corporation , West Chester, Pennsylvania.
5
5 Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.

Abstract

BACKGROUND:

Worldwide, ∼1 million people manage their type 1 diabetes with an insulin pump and a continuous subcutaneous insulin infusion (CSII) catheter. Patients routinely insert a new catheter every 2-3 days due to increasing variability of insulin absorption over time. Catheter insertion and maintenance damage capillaries, lymphatics, cells, and connective tissue leading to an acute inflammatory response.

METHODS:

We compared an investigational CSII catheter (IC) and a commercial CSII catheter (CC) regarding insulin absorption pharmacokinetics (PK) and tissue inflammation. The two different catheter designs were implanted into the subcutaneous tissue of six swine for 5 days. Insulin boluses were given on days 1, 3, and 5 of wear-time to assess PK. Tissue around catheters was excised and stained to visualize inflammation and morphological changes of adjacent tissue.

RESULTS:

Insulin absorption was better when infused through a CC with highest Cmax and fastest tmax values on day 5 of catheter wear-time. Both catheter types produced high intra- and intersubject day-to-day insulin absorption variability. The IC caused significantly more tissue disruption and lead to irregular changes in tissue morphology. Both catheter types were surrounded by a layer of inflammatory tissue that varied in composition, thickness, and density over time. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion.

CONCLUSIONS:

Insulin absorption variability could be attributed to the layer of inflammatory tissue, which may function as a mechanical barrier to insulin flow into adjacent vascular tissue. The impact of the acute inflammatory tissue response on insulin absorption has to be considered in future catheter designs. A catheter that was manually inserted by pushing a sharp tip through the skin caused more trauma and variability than a 90° Teflon cannula with automated insertion.

KEYWORDS:

Adipose tissue inflammation; CSII catheter; CSII therapy; Inflammatory response; Insulin absorption variability; Insulin pharmacokinetics

PMID:
28981324
PMCID:
PMC5689134
DOI:
10.1089/dia.2017.0175
[Indexed for MEDLINE]
Free PMC Article

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