The initial purpose for the development of long-acting insulin preparations was to minimize the number of daily injections needed for glycemic control. Ideally, the action of such an insulin preparation should reflect naturally occurring changes in insulin requirements throughout the day. This would be particularly important during the overnight period, when longer-acting insulins are required to suppress endogenous glucose production. Additionally, the kinetics and dynamics should be highly reproducible so that day-to-day variation in absorption/activity is as low as possible.
Two intermediate-acting insulins have been widely used: the zinc-precipitated Lente insulin and the protamine-precipitated NPH insulin (5). Although pork insulin preparations are still available, since the introduction of human insulin to the U.S. market the use of animal insulin has markedly decreased. Overall, human insulin has a somewhat earlier peak of onset and shorter duration of action compared with pork insulin. However, the clinical implications of this finding are probably small; clinical studies have shown essentially equivalent glycemic control with pork and human insulin. Only human insulins are discussed in the remainder of this section.
called Ultralente. Commercial preparations of Lente insulin are standardized to a mixture of 30% Semilente and 70% Ultralente. Early formulations of this mixture combined beef and pork insulin, because the conditions caused the porcine insulin to become amorphous and the beef to crystallize (5). Human Lente is now available. Its kinetics of action are similar to those of NPH, although it peaks a little more slowly than the NPH, and a biphasic pattern in the systemic insulin appearance of Lente insulin has been described, probably due to the different kinetics of the amorphous and crystalline compounds. Duration of action is 13-16 hours, and the maximal blood-glucose-lowering effect is seen around 6 hours after injection. It is noteworthy that the zinc insulins are not miscible with non-zinc insulins such as Regular or NPH, because the high zinc content can lead to unpredictable microcrystallization and prolongation of the effect of the non-zinc insulin.
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