Mimicry of the Early Phase Insulin Response in Humans with Rapidly Available Inhaled Insulin Accelerates Postprandial Glucose Disposal Compared to Slower Bioavailable Insulin
Abstract Number: 1373-P
Authors: ANDERS H. BOSS, MARSHALL L. GRANT, WAYMAN W. CHEATHAM
Institutions: Danbury, CT
Results: The loss of the first or early phase of the meal related insulin response is an early finding in patients who develop type 2 diabetes mellitus, but the physiological significance of this loss has not been fully understood.
Using Technosphere®/ Insulin (MannKind Corporation) (TI ) to mimic the early phase response, we studied the relationship between time, insulin concentration and glucose elimination rate (GIR) in a group of 12 subjects with type 2 diabetes, during a euglycemic insulin clamp. Each subject received 24 IU subcutaneous insulin (SC) (Actrapid, Novo Nordisk) or 48 U TI on separate study days in a cross-over design. Glucose disposal rates were reflected by the glucose infusion rate (GIR) required to maintain a target blood glucose of 120 mg/dl during the 540 min study period.
A 48 U dose of TI provided a mean Cmax of 114.8 ±44.1(SD) mU/L with a median Tmax of +15 min, compared to a Cmax of 63 ±10.1 mU/L and Tmax of +150 min after 24 IU SC insulin. TI reached maximal GIR values of 3.33 ±1.35 mg/kg/min, at +45 min, while the SC dose was related to a rate of only 1.58 ±1.03 mg/kg/min by that time. Moreover, the GIR for SC continued to climb to reach its peak of 3.38 ±1.45 mg/kg/min at +255 min. Once maximal insulin effect was reached, the concentration - effect relationship to GIR was the same for TI and SC.
The observed phenomenon does not appear to be caused by differences in the dose- effect relationship for the two insulin types, but reflects a difference in response when the increment in insulin concentration is more modest over time as opposed to the more rapid bioavailable insulin provided by Technosphere/ Insulin. This finding may have consequences for further understanding and investigation of postprandial glucose control.