Variability of Insulin Action: Does It Matter?

Background: Repeat SC injection of identical insulin doses does not induce an identical metabolic effect in patients with diabetes. This concept hampers practical insulin therapy tremendously.Objective: The aim of this article is to briefly and critically review the available literature on the variability of insulin action.Methods: There are only limited numbers of clinical-experimental and clinical studies focusing on the variability of insulin action; therefore, no formal literature search was performed. However, the available studies, along with their references, provided the basis for our findings.Results: Insulin absorption from the SC depot is mainly determined by local blood flow, and many factors affect blood flow. The metabolic effect of absorbed insulin depends on a patient's insulin sensitivity, which is highly variable both intraindividually and interindividually. SC injection of prandial insulin shows an intraindividual coefficient of variation (CV) of insulin action of 15% to 25% and an interindividual CV of 20% to 45% under experimental conditions. The intraindividual variability of insulin action for intermediate-acting/basal insulin is not much higher at 25% to 35% than that of prandial insulin. The variability of the currently available soluble long-acting insulin analogues is reduced compared with neutral protamine Hagedorn insulin in most but not all studies. Although other routes of insulin application (eg, inhalation) might provide an opportunity to reduce the variability of insulin action, the intraindividual variability of metabolic effect observed after inhalation of insulin (15%–30%) was comparable to that seen after SC administration of prandial insulin (15%–25%).Conclusions: The variability of insulin action is clinically highly relevant; however, an intensive scientific investigation of this topic is lacking. Nonetheless, this research might well enable the development of insulin formulations or insulin application techniques that would help reduce this disturbing aspect of insulin therapy.