Table 4.

Factors related to the injection technique that influence insulin pharmacokinetics and international recommendations on insulin delivery that aim at reducing pharmacokinetic variability between injections.

Factor	Effect on insulin pharmacokinetics	International recommendations on insulin delivery [141]
Needle size	Age and gender, for example, have significant influence on the anthropometry in people with diabetes and should therefore be taken into account when choosing needle length and dosing strategy [158] in order to reduce the risk of intramuscular injection	Use of the shortest needles is recommended (the 4 mm pen and 6 mm syringe needle). In order to decrease the risk of intramuscular injections, the 4 mm needle should be used for injection in children and young adults. Lifting of a skinfold prior to injection or injection at a 45° angle may further reduce the risk of intramuscular injection
Time before withdrawal	Rapid withdrawal may result in loss of insulin and increased pharmacokinetic variability between injections [141]	With use of insulin pens, patients should count to 10 after the plunger is fully depressed before removing the needle from the skin
Dispersion	Dispersion of the injection volume gives rise to a more rapid absorption [108]	Larger doses may be split to reduce the volume of insulin and avoid leakage
Mixing	Inadequate resuspension is a problem with insulin suspensions (e.g., NPH insulin) and contributes to pharmacokinetic variability between injections [82, 141]	It is recommended to gently roll and tip cloudy insulin until the crystals are resuspended (the solution becomes milk white)
Needle reuse	Reuse of needles increases the risk of lipodystrophy [160, 161]	Reusing insulin needles is not an optimal injection practice, and patients should be discouraged from doing so
Rotation	Rotation between injection sites reduces the prevalence of lipodystrophy [141, 160, 161], but for a number of insulin preparations, rotation also elicits different pharmacokinetic and pharmacodynamic responses [111, 115, 118, 122–125, 130]	Patients should be encouraged to avoid injecting into areas of lipohypertrophy, and injections should be rotated by injecting at least 1 cm from previous injection (i.e., within the same injection region)