Variability of insulin absorption is perhaps the greatest obstacle to replicating physiologic insulin secretion. Among the many factors that affect insulin absorption and availability (Table 3) are injection site; the timing, type, or dose of insulin used; and physical activity. Day-to-day intraindividual variation in insulin absorption is approximately 25%, and the variation between individuals may be as high as 50%. One reason for this is that large doses of human insulin form an insulin depot, which can unpredictably prolong duration of action; this is less of an issue with rapid-acting insulin analogues, however. Patients injecting 40 U of NPH insulin into their abdomen before breakfast, for example, may have a markedly different onset and peak of action than the same patients injecting 20 U of NPH in their thigh in the evening; mixing insulin lispro with the morning NPH dose and regular insulin with the evening dose would also lead to further variation, especially if the NPH is not resuspended properly. In general, any strategy that increases the consistency of delivery should decrease glucose fluctuations; and insulin regimens that emphasize shorter-acting insulins are more reproducible in their effects on blood glucose levels.
|Site of injection||Abdominal injection (particularly if above the umbilicus) results in the quickest absorption; arm injection results in quicker absorption than thigh or hip injection.|
|Depth of injection||Intramuscular injections are absorbed more rapidly than subcutaneous injections.|
|Insulin concentration||U-40 insulin (40 units per mL) is absorbed more rapid than U-100 insulin (100 units per mL).|
|Insulin dose||Higher doses have prolonged durations of action compared with lower doses.|
|Insulin mixing||Regular insulin maintains its potency and time-action profile when it is mixed with NPH insulin; no insulin should be mixed with insulin glargine or insulin detemir|
|Exercise||Exercising a muscle group before injecting insulin into that area increases the rate of insulin absorption.|
|Heat application or Massage||Local application of heat or massage after an insulin injection increases the rate of insulin absorption.|
Insulin pens are convenient and their use may avert some insulin errors, but insulin cartridges for pens are more costly than insulin in vials. An insulin pump using only a rapid-acting insulin analogue significantly reduces variability. Like multiple-injection regimens, use of an insulin pump requires frequent blood glucose monitoring, as well as a back-up method of insulin administration, and attention to mechanical and injection site issues.