Subcutaneous absorption of insulin in insulin-dependent diabetic patients. Influence of species, physico-chemical properties of insulin and physiological factors

Abstract

One major problem encountered when treating diabetic patients with insulin is the very large inter- and intra-individual variability in subcutaneous insulin absorption, a major contributory factor in the variability of the blood glucose level. Thus, to optimize insulin treatment the factors influencing the absorption have to be known and possibly utilized. The different types of insulin ("short-acting", "intermediate-acting" and "long-acting") have different times of action. "Short-acting" and "intermediate-acting" human insulin are probably absorbed slightly faster than porcine (and bovine) insulin. "Long-acting" human insulin is absorbed significantly faster than bovine insulin. More concentrated "short-acting" insulin (100 IU/ml) is absorbed slightly slower than less concentrated insulins (40 IU/ml). The absorption of "intermediate-acting" and "long-acting" insulin is dose-dependent, with a decreasing absorption rate with increasing dose of insulin. Insulin is administered subcutaneously either by injection or by using an infusion pump. The injection technique influences the absorption rate. Giving a continuous subcutaneous insulin infusion as a basal rate infusion, a depot is built-up. The building-up and the size of the depot, as well as the blood glucose and plasma insulin levels during steady-state conditions, are independent of the pulse-rate interval of the pump used (5 min vs 1 h). The size of the steady-state depot is constant during constant conditions but inversely correlated to the local subcutaneous blood flow and directly correlated to the infusion rate. An increase or decrease in the infusion rate during a basal rate infusion will after a delay of 2-3 h induce corresponding changes in the insulin absorption rate from the depot. After termination of the infusion, the insulin depot will still provide some insulin supply for 2-3 h. During the continuous infusion, the pharmacokinetics of the superimposed preprandial boluses will resemble injections of soluble insulin. The inter- and intra-individual variability in the insulin absorption, even when giving the same type, species, concentration and dose of insulin, is presumably primarily due to different and changing diffusion conditions in the subcutaneous tissue. Some factors which influence the diffusion conditions include exercise, local massage and, especially, local subcutaneous blood flow. Alterations in the blood flow induce, with a hyperbolic relationship, changes in the same direction in the absorption rate of injected and infused "short-acting" insulin and of injected "intermediate-acting" insulin. Several factors have been shown to influence both subcutaneous blood flow and insulin absorption, e.g. injection site, skinfold thickness, smoking, orthostatic changes, ketosis and ambient temperature.(ABSTRACT TRUNCATED AT 400 WORDS)