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Click to add/remove this article to your list of 'My Favorites' Mimicry of the Early Phase Insulin Response in Humans with Rapidly Available Inhaled Insulin Accelerates Postprandial Glucose Disposal Compared to Slower Bioavailable Insulin

Year: 2005

Abstract Number: 1373-P


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.