Background and Aims

Capillary Biomedical Inc. (CapBio) has developed an improved, kink-resistant, angled insulin infusion set (IIS) with a softer cannula material and 3 additional side holes for better insulin delivery. This study aimed to compare a regular 90° Teflon IIS (T90) with the CapBio improved IIS.

Methods

40 T90 and 48 CapBio IISs were inserted subcutaneously every other day for 2 weeks in 11 swine and connected to an insulin pump (basal/bolus pattern). After 2 weeks, the tissue surrounding the cannulas was excised and kinking within the tissue determined using micro-CT. The specimens were processed and stained with Masson’s Trichrome to assess the area of inflammation (AI) and thickness of inflammatory layer (LT) surrounding the cannula. Data were analyzed using Fisher’s Exact, ANOVA GLM, Kruskal Wallis, and post hoc Tukey HSD and Dwass-Steel-Chritchlow-Fligner tests.

Results

AI and LT were consistently higher using T90, with statistically significant differences after 6 days of IIS wear time. On average, the AI was reduced by 52.6% and the LT by 66.3% using the angled CapBio IIS. While 32.5% (13/40) of T90 IISs kinked (=bend in cannula >90°), only 2.1% (1/47) of the CapBio IISs kinked (p<0.001).

Conclusions

The data suggest that the new cannula design of the CapBio IIS causes less tissue trauma compared to a regular 90° Teflon IIS between 2 days and 2 weeks post insertion and is resistant to kinking. These results are supportive of the objective of extending infusion set wear through changes to the material and mechanical design of traditional IIS cannulas.

Background and Aims

The evidence for recommendations to change insulin infusion sets (IIS) at least every 2-3 days is limited. In this study, an extended indwelling time of IIS and its impact on glycemic control were investigated.

Methods

Forty subjects were advised to wear IIS for up to 7 days in daily life. Each subject used two YpsoPump^® Orbit^®soft (soft cannula) and two YpsoPump^® Orbit^®micro (steel needle) IIS. Early replacements were documented and glucose levels were monitored (Dexcom G5^TM Mobile). For IIS surviving 7 days, subjects’ glycemic control was compared between days.

Results

Of 160 tested IIS, 66% were used for 7 days. Mean wearing time was 6.2±1.5 days with no considerable difference between steel and soft cannula IIS. Main early replacements reasons were suspected occlusions (n=30) and adhesive failure (n=7). Mean glucose concentration (n=105 IIS) was 146±21 mg/dl during the first 3 days and 148±18 mg/dl during the whole 7 days and coefficient of variation was 34±7% vs. 33±5%. Daily insulin demand was 40±11 U (day 1-3) vs. 41±11 U (day 1-7). Infusion site reactions were mild and resolved within a few days without treatment. No infusion site infection occurred.

Conclusions

Prolonged indwelling of IIS did not have a clinically relevant impact on glycemic control. IIS tolerability was good and appeared comparable to 3-day use. An individual wearing time of up to 7 days is possible if no obvious reason for earlier change such as occlusion, adhesive failure or inflammation occurs.

Background and Aims

This study was intended to test if a new fluid path design (H-Cap Connector) could extend the infusion set wear time. Both H-Cap extended wear set (HEWS) and control infusion set MiniMed™ Quick-set™(QS, a 3-day set worn upto 7-days in this study) were compared for percent of sets reaching 7-day use without set failure for insulin pump therapy in type 1 diabetes mellitus.

Methods

Forty subjects were recruited with a target of 20 subjects completing the study. This was a randomized, open-labeled, crossover study, with each subject being asked to wear 4 HEWS and 4 regular QS infusion sets (both from Medtronic MiniMed, Northridge, CA) until the infusion set failed or 7-day use was reached.

Results

Four subjects did not participate beyond randomization during the study. One subject withdrew after 4 wears. There were 144 wears of H-Cap extended wear set and 140 wears of QS. When an infusion set was successfully used for 7 days, there was no increase in hyperglycemia or daily insulin requirements. After 7 days, the failure rate was 50.7% for QS and 30.6% for HEWS.

Conclusions

Clinical data obtained from this prospective, randomized, controlled, one site study demonstrates significant higher 7-day survival of the HEWS in comparison to regular Quick-set in this study or in previously reported study on QS in Patel et. al. study [1]. 69.4% of the HEWS used, survived 7 days.

[1] Patel PJ, Benasi K, Ferrari G, et al. Randomized trial of infusion set function: steel versus teflon. Diabetes Technol Ther. 2014; 16:15-19.

Background and Aims

Continuous subcutaneous insulin infusion (CSII) is only FDA approved for 3 days. We believe that excipient-induced tissue reactions are responsible for the short-lived CSII functionality, skin complications and pharmacokinetic variation. The objective is to determine the role of inflammation in insulin-excipient induced tissue reaction in both murine and porcine models.

Methods

We modified the classic murine “air pouch” model to investigate CSII causes and mechanisms associated with compromised blood glucose control. The addition of an inline home-made filter also permits the removal of excipients prior to insulin infusion into the mouse air pouch. Tissue responses to insulin infusion, excipients, excipient-free insulin and control solutions (e.g. saline) over a 7-day period were investigated. These studies were also extended into a pre-clinical porcine animal model.

Results

Our data indicate that 1) phenol-based insulin diluents trigger infusion site inflammation in both murine and porcine models; 2) that the acute inflammation alters infusion site tissue architecture and functions and 3) the resulting fibrosis eliminates future use of the same infusion site. Pharmacokinetic evaluations demonstrated that insulin absorption is delayed and maximum plasma concentration is decreased in inflamed tissue suggesting a role of inflammatory cells in insulin absorption. In-line removal of excipients immediately prior to insulin infusion minimized the loss of insulin function as well as insulin infusion associated tissue inflammation and subsequent fibrosis at CSII infusion sites.

Conclusions

These studies directly demonstrate the toxicity of excipients in commercial insulin formulations in both murine and porcine models.