CONCLUSIONS
The current study demonstrates that a therapeutic dose of NPH insulin (0.35 units/kg) commonly used in patients with T1DM results in quite different PK/PD depending on whether NPH insulin is appropriately resuspended before
subcutaneous injection. Compared with resuspended NPH insulin, nonresuspended NPH insulin may result in either potentiated or reduced insulin PK/PD depending on the position of the pen before injection (held horizontally or
vertically with tip either up or down).At one extreme, when the pen is held vertically tip down with no resuspension before injection (R- down), the injected NPH insulin is predominantly the cloudy part (Fig. 1), which is rich in insulin crystals.
In this case, plasma insulin concentration, insulin effect (GIR), and duration of action are potentiated compared with the other extreme of nonresuspended NPH insulin, with the predominant injected part being clear (theoretically no
or very few insulin crystals [R- horizontal and R- up]). Within-subject variability of PK/PD of NPH insulin is elevated both when all four suspension conditions are considered and when the resuspended NPH insulin is compared with one occasion
of nonresuspension (Table 2). In contrast to these characteristics of the insoluble NPH insulin, the modern longacting insulin analogs (1,2) are soluble and, therefore, do not need resuspension before injection. For this reason, they are
expected to be less variable than NPH insulin.