Pharmacokinetics of insulin lispro in type 2 diabetes during closed-loop insulin delivery.

Abstract

Insulin pharmacokinetics is not well understood during continuous subcutaneous insulin infusion in type 2 diabetes (T2D). We analyzed data collected in 11 subjects with T2D [6 male, 9 white European and two of Indian ethnicity; age 59.7(12.1) years, BMI 30.1(3.9) kg/m(2), fasting C-peptide 1002.2(365.8) pmol/l, fasting plasma glucose 9.6(2.2) mmol/l, diabetes duration 8.0(6.2) years and HbA1c 8.3(0.8)%; mean(SD)] who underwent a 24-h study investigating closed-loop insulin delivery at the Wellcome Trust Clinical Research Facility, Cambridge, UK. Subcutaneous delivery of insulin lispro was modulated every 15 min according to a model predictive control algorithm. Two complementary insulin assays facilitated discrimination between exogenous (lispro) and endogenous plasma insulin concentrations measured every 15-60 min. Lispro pharmacokinetics was represented by a linear two-compartment model whilst parameters were estimated using a Bayesian approach applying a closed-form model solution. The time-to-peak of lispro absorption (t(max)) was 109.6 (75.5-120.5) min [median (interquartile range)] and the metabolic clearance rate (MCR(I)) 1.26 (0.87-1.56)×10(-2) l/kg/min. MCR(I) was negatively correlated with fasting C-peptide (r(s)=-0.84; P=.001) and with fasting plasma insulin concentration (r(s)=-0.79; P=.004). In conclusion, compartmental modelling adequately represents lispro kinetics during continuous subcutaneous insulin infusion in T2D. Fasting plasma C-peptide or fasting insulin may be predictive of lispro metabolic clearance rate in T2D but further investigations are warranted.

• Authors: Yue Ruan, Hood Thabit, Kavita Kumareswaran, Roman Hovorka
• Journal: Computer methods and programs in biomedicine (Comput Methods Programs Biomed) Vol. 117 Issue 2 Pg. 298-307 (Nov 2014) ISSN: 1872-7565 [Electronic] Ireland
• PMID: 25092225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Blood Glucose
• Insulin Lispro

Topics

• Blood Glucose (drug effects, metabolism)
• Computer Simulation
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Drug Therapy, Computer-Assisted (methods)
• Feedback, Physiological
• Humans
• Insulin Infusion Systems
• Insulin Lispro (administration & dosage, pharmacokinetics)
• Male
• Metabolic Clearance Rate
• Middle Aged
• Models, Biological
• Reproducibility of Results
• Sensitivity and Specificity