Effect of Injection Site Cooling and Warming on Insulin Glargine Pharmacokinetics and Pharmacodynamics

Abstract

Background: In type 1 diabetes (T1D), closed-loop systems provide excellent overnight fasting blood glucose control by adjusting the insulin infusion rate based on corresponding changes in sensor glucose levels. In patients on multiple daily insulin (MDI) injections, such control in overnight glucose levels has not been possible due to the inability to alter the absorption rate of long-acting insulin after injection. In this study, we tested the hypothesis that increases/decreases of fasting glucose levels could be achieved by cooling/warming the skin around the injection site, which would result in lower/higher Glargine absorption rates from its subcutaneous depot. Methods: Fourteen subjects with T1D (4 females; age 39.6 ± 16.7 years, HbA1c 7.8 ± 1.1%, BMI 25.4 ± 2.8 kg/m2) on MDI therapy underwent fasting pharmacokinetic and pharmacodynamic studies that started at ~8 am and lasted 240 min on 3 separate days in random order: a control day without warming or cooling of the injection site and two experimental days, one day with injection site warming and the other with cooling. Results: Cooling the skin around the glargine injection site reduced insulin concentrations by >40% (P