Evaluation of Subcutaneous Insulin Absorption in Swine over 8 Days Using a Commercial Catheter
Location
Philadelphia, PA
Start Date
9-5-2018 1:00 PM
Description
Background: Over one million type I and end-stage type II diabetics around the world rely on an insulin pump with a continuous subcutaneous insulin infusion catheter (CSII) system to control their blood glucose. Unfortunately, insulin uptake from subcutaneous tissue is variable and may depend on local capillary circulation, lymphatic absorption, and inflammation around the catheter site. Catheters are also subject to mechanical issues and are often replaced prior to 3 days (FDA approved use). This study investigated the day-to-day insulin absorption variability with extended catheter use over an 8 day period.
Methods: Using the hyperinsulinemic-euglycemic glucose clamp technique, we conducted a pilot study in 2 swine to assess insulin uptake via CSII catheters over an 8 day period. Three CSII catheter sets were tested separately each week in each animal. On the first day of each experiment, a commercial Teflon catheter was inserted into the swine’s mid abdominal subcutaneous tissue under general anesthesia. Commercial insulin lispro (Humalin) was administered and glucose clamps were performed on days 2, 4, 7, and 8 to measure blood glucose response. D10 adjusted at 5 min intervals to maintain BG at 85 mg/dL ±10%. PK/PD data were collected for each study post insulin bolus administration for 240 min. Glucose infusion rate (GIR) and AUC were used as adjuncts for insulin uptake. The catheters and surrounding subcutaneous tissue were excised on day 8 for histological analysis. Data were analyzed using ANOVA with repeated measures with p<0.05 set for statistical significance.
Results: A total of 24 clamps were successfully performed in 2 swine with one catheter/swine/wk studied on the 4 different days with mean BG maintained between 83.7-86.4 mg/dL for all experiments. GIR curves were significantly (p<0.001) different from day to day in the 2 animals. Post hoc analysis showed day 7 to have significantly lower insulin absorption compared to days 2, 4, and 8. Maximum GIR was achieved on Days 2 and 4 with a GIR Tmax of ~30 min compared to 45 min on day 7. The AUCGIR showed a similar effect as the GIR curves and the AUC coefficients of variation (CV) between the 2 swine were 29%, 5%, 36%,18% for days 2, 4, 7, and 8, respectively.
Conclusions: The results of this pilot study show GIR to be higher during the first 4 days post catheter insertion with a significant decrease occurring on day 7. The most interesting finding was that insulin absorption on day 8 was similar to days 2 and 4, which is about 2 times longer than the FDA approved use of current commercial catheters. The GIR Tmax was also achieved within 30 min on day 8 compared to 45 min on day 7. The between animal day-to-day variability ranged from 5-36% which is comparable to insulin absorption variability reported in human studies.
Embargo Period
5-30-2018
Evaluation of Subcutaneous Insulin Absorption in Swine over 8 Days Using a Commercial Catheter
Philadelphia, PA
Background: Over one million type I and end-stage type II diabetics around the world rely on an insulin pump with a continuous subcutaneous insulin infusion catheter (CSII) system to control their blood glucose. Unfortunately, insulin uptake from subcutaneous tissue is variable and may depend on local capillary circulation, lymphatic absorption, and inflammation around the catheter site. Catheters are also subject to mechanical issues and are often replaced prior to 3 days (FDA approved use). This study investigated the day-to-day insulin absorption variability with extended catheter use over an 8 day period.
Methods: Using the hyperinsulinemic-euglycemic glucose clamp technique, we conducted a pilot study in 2 swine to assess insulin uptake via CSII catheters over an 8 day period. Three CSII catheter sets were tested separately each week in each animal. On the first day of each experiment, a commercial Teflon catheter was inserted into the swine’s mid abdominal subcutaneous tissue under general anesthesia. Commercial insulin lispro (Humalin) was administered and glucose clamps were performed on days 2, 4, 7, and 8 to measure blood glucose response. D10 adjusted at 5 min intervals to maintain BG at 85 mg/dL ±10%. PK/PD data were collected for each study post insulin bolus administration for 240 min. Glucose infusion rate (GIR) and AUC were used as adjuncts for insulin uptake. The catheters and surrounding subcutaneous tissue were excised on day 8 for histological analysis. Data were analyzed using ANOVA with repeated measures with p<0.05 set for statistical significance.
Results: A total of 24 clamps were successfully performed in 2 swine with one catheter/swine/wk studied on the 4 different days with mean BG maintained between 83.7-86.4 mg/dL for all experiments. GIR curves were significantly (p<0.001) different from day to day in the 2 animals. Post hoc analysis showed day 7 to have significantly lower insulin absorption compared to days 2, 4, and 8. Maximum GIR was achieved on Days 2 and 4 with a GIR Tmax of ~30 min compared to 45 min on day 7. The AUCGIR showed a similar effect as the GIR curves and the AUC coefficients of variation (CV) between the 2 swine were 29%, 5%, 36%,18% for days 2, 4, 7, and 8, respectively.
Conclusions: The results of this pilot study show GIR to be higher during the first 4 days post catheter insertion with a significant decrease occurring on day 7. The most interesting finding was that insulin absorption on day 8 was similar to days 2 and 4, which is about 2 times longer than the FDA approved use of current commercial catheters. The GIR Tmax was also achieved within 30 min on day 8 compared to 45 min on day 7. The between animal day-to-day variability ranged from 5-36% which is comparable to insulin absorption variability reported in human studies.