Abstract

Background and aims: The pharmacokinetics and pharmacodynamics
of the rapid-acting insulin analogues aspart and lispro have been wellcharacterised and are considered comparable, with analogues displaying
similarly large inter-personal variability in action-time profiles following
subcutaneous injection. However, it is unknown whether, and which,
personal characteristics explain inter-personal variability in rapid-acting
insulin kinetics. Therefore, we compared serum insulin kinetics following
subcutaneous injection of prandially-administered rapid-acting insulin in
people with type 1 diabetes (T1D) treated on multiple daily injections.
Materials and methods: Thirty-two individuals (mean±SD: 31±6.89
years, 26.03±4.82 kg/m2
) with T1D, treated with multiple daily injections
consisting of rapid-acting insulins aspart (n=20) and lispro (n=12), and
basal-insulins glargine (n=23) and detemir (n=9) were recruited. Subjects
attended the laboratory on a single morning (~8am) following an overnight fast and self-administered a subcutaneous dose of rapid-acting insulin to the lower abdomen immediately before the consumption of a
standardised meal. Rapid-acting insulin doses were standardised and
calculated using the carbohydrate counting method; basal insulin
remained unchanged. Serum insulin levels were measured for 6-hours
following administration. Regression analysis was used to assess associations between serum insulin kinetics and personal characteristics.
Results: Serum insulin AUC was positively associated with age (p=0.006,
95%CI -85.6 to -15.9), duration of diabetes (p<0.001, 95%CI -70.1 to -
22.6), HbA1c (p=0.001, CI -71.4 to -12.0), BMI (p=0.006, 95%CI -120.3 to
-19.8), and circulating fibrinogen concentrations (p=0.002, 95%CI -0.50 to
-0.12) and negatively associated with estimated glucose disposal rate
(eGDR; p=0.008, 95%CI 51.4 to 231.8). Bolus dose was positively associated with age (p<0.001, 95%CI 0.141 to 0.384), duration of diabetes
(p<0.001, 95%CI 0.092 to 0.278), HbA1c (p=0.001, 95%CI 0.088 to
0.287), and BMI (p<0.001, 95%CI 0.210 to 0.553) and negatively associated with eGDR (p=0.002; 95%CI -0.938 to -0.243), but not serum insulin
AUC, iAUC, peak, or time to peak (p>0.05).
Conclusion: We show for the first time that inter-personal variability in
rapid-acting insulin kinetics are influenced by personal characteristics
including age, diabetes duration, HbA1c, BMI, eGDR, and circulating
fibrinogen concentrations in people with T1D. These data yield important
implications for determining patient-specific rapid-acting insulin dosing
recommendations which could lead to more effective self-management
strategies