Progressive Acceleration of Insulin Exposure Over 7 Days of Infusion Set Wear

Insulin exposure varies over 3 days of insulin infusion set (IIS) wear making day-to-day insulin dosing challenging for people with diabetes (PWD). Here we report insulin pharmacodynamic (PD) and pharmacokinetic (PK) data extending these observations to 7 days of IIS wear. PWD (A1C <= 8.5%, C-peptide <0.6 nmol/L, >= 6 months pump use) were enrolled in a crossover euglycemic clamp pilot study comparing conventional Teflon angled IISs with an investigational extended-wear IIS. PK/PD data from six participants were obtained for 5 h postbolus. Although PD data were unstable, PK profiles (pooled data from both groups) of insulin lispro (0.15 U/kg bolus) showed statistically significant progressive decreases from days 0 to 7 for t(max) (P < 0.001), C-max (P < 0.05), and mean residence time (P < 0.0001). Area under the insulin concentration curve (AUC(0-300)) declined by similar to 24% from days 0 to 7 (P < 0.05). These results confirm/extend previous observations showing progressive acceleration of insulin exposure over IIS wear time. This may have implications for PWD and designers of closed-loop algorithms, although larger studies are necessary to confirm this. The study was registered in clinicaltrials.gov (NCT04398030).

Automated summary

Insulin exposure varies over the course of insulin infusion set (IIS) wear, posing challenges for insulin dosing in people with diabetes. This study extends previous observations by examining 7 days of IIS wear and reports insulin pharmacodynamic and pharmacokinetic data. The results show progressive decreases in insulin t(max), C-max, and mean residence time, as well as a decline in the area under the insulin concentration curve (AUC(0-300)). These findings have implications for individuals with diabetes and the development of closed-loop algorithms, although further research is needed to confirm these findings. The study was registered in clinicaltrials.gov (NCT04398030).