Aim: To determine the time to steady state insulin pharmacokinetics following a clinically-relevant increment and decrement in subcutaneous basal insulin infusion rate (BIIR).
Background: Minimal data guides clinical practice regarding effects of BIIR adjustment on circulating insulin1,2,3. There is a reliance on extrapolation of bolus data which suggests an approximately one hour lag time to reach maximum insulin levels4.
Method: Twelve adults with type 1 diabetes (50% female, age range 21–57 years) on insulin pump therapy with stable overnight BIIR were studied fasting over two stages. Standardised insulin, insulin pump and pump consumables were utilised. Following 1 hour rest, BIIR was altered by 0.2 units/hour (increment in first study; decrement in second). Venous samples were collected at 15 minute intervals from 60 minutes prior to BIIR change until 300 minutes post-change for plasma glucose and insulin levels (Millipore radioimmunoassay, intra- and inter-assay CVs 2.5% and 3.3%). Plasma was pre-treated with polyethylene glycol to precipitate bound insulin when antibodies were present.
Results: Time to 90% steady state insulin level post-increment was mean (95% confidence interval) 186 (149,222) minutes, and time to 80% steady state was 156 (130,181) minutes. Free insulin levels were unchanged post-increment in two subjects with insulin antibodies. No circulating insulin reduction was apparent 5 hours post-decrement.
Conclusion: Bolus pharmacokinetic data have limited applicability to BIIR adjustments. Our findings question the clinical benefit associated with more than six basal rates in a day, suggest that the effects of insulin antibodies may impact upon responses to basal rates changes, and may have implications for closed loop algorithm design as most algorithms respond symmetrically with increments and decrements when glucose is above or below target.