Exaggerated postprandial glycemic excursions in the first hours after a meal and an increased risk of late postprandial hypoglycemia are commonly observed following bolus injections of regular human insulin due to the delayed peak and the prolonged duration of action of this insulin preparation. 1 In contrast, plasma insulin concentrations peak earlier (generally thought to be within the first hour) and plasma insulin concentrations return to baseline more quickly with rapid-acting insulin analogs (RAIAs).2 Nevertheless, even with the more favorable absorption characteristics of RAIAs, postmeal hyperglycemia remains difficult to control in insulin-requiring diabetic patients due to delays in the peak action of these analogs to 120 or more minutes after injection. The time to peak insulin concentrations following bolus injections of both human regular and RAIAs are dose dependent, 3 with higher doses leading to delayed peaks and prolonged duration of action of these insulins. Moreover, the FDA-approved prescribing information package inserts for RAIAs state that the time course of action of these insulins may vary in different individuals or at different times in the same individual. 4 Such variations in insulin action are dependent on many conditions, including the site of injection, local blood supply and local skin temperature. 4 The impact of the site of injection on the rate of absorption of regular insulin (ie, abdomen > arm > leg) was first described by Koivisto and Felig in 1980. 5 They also demonstrated that increasing the skin temperature to 30°C to 37°C via sauna use increased the rate of insulin absorption and 578881D STXXX10.1177/1932296815578881Journal Abstract Background: Delays in the time-action profiles of premeal boluses of rapid-acting insulin analogs contribute to early postmeal hyperglycemia in patients with diabetes. We tested whether applying local heat to skin around the injection site to increase the rate of insulin absorption reduces postprandial hyperglycemia in patients with type 2 diabetes. Methods: Fourteen patients with type 2 diabetes (4 females; age 61.6 ± 8.4 years, HbA1c 8.42 ± 1.13%; BMI 29.10 ± 5.61 kg/m 2 ) on intensified insulin therapy underwent 5-hour meal tolerance tests (MTTs) with a standardized liquid meal after an overnight fast on 2 study days. Subjects injected 0.2 U/kg of insulin aspart or lispro subcutaneously into the abdominal skin on both days with and without the use of the InsuPad device. Results: Following the premeal bolus injection of rapid-acting insulin analog, infusion site warming led to a rise in plasma insulin levels to peak concentrations that were significantly earlier than without skin warming (mean ± SD 52 ± 26.7 vs 80 ± 51.3 minutes, P < .005) as well as increase in plasma insulin levels during the first hour after injection (mean ± SD 63.5 ± 32.7 IU vs 48.0 ± 25.0 uU.min/ml, P = .019). As a result, the area under the curve of the postprandial glucose excursion during the first 2 hours (the primary study outcome) and the entire 5 hours after ...