The new insulins. Their characteristics and clinical indications.

Abstract

In the past 10 years the techniques of gel filtration and ion exchange chromatography have made available insulins of markedly enhanced purity. These highly purified insulins have made immunological insulin resistance a rarity, and result in absent or clinically insignificant levels of insulin antibodies in insulin-treated diabetics. Insulin allergy has not been reported with highly purified insulins alone, and is rare even when the patient has previously received recrystallised insulin. Generalised allergic reactions to insulin and insulin resistance are associated with the enhanced immunological reaction to intermittent insulin therapy. The use of highly purified insulins for short courses of treatment is therefore mandatory, particularly in patients with infections. Injection-site lipoatrophy, a relatively common occurrence with the older insulins, disappears on changing to highly purified preparations. Following a change to highly purified insulins, insulin dose requirements will fall gradually with insulin antibody levels. When switching from conventional beef to highly purified pork insulins, a more immediate change in dose requirements may occur so that prospective reductions in insulin dose are indicated. It is still uncertain whether moderate levels of insulin antibodies are associated with any difference in metabolic control. This is partly a reflection of difficulties in measuring diabetic control, and partly a lack of properly designed studies. Current insulins of both older and newer types give plasma insulin profiles that are far from physiological. Insulin antibodies cross the placenta and may contribute to increased fetal insulin secretion and neonatal hypoglycaemia. Pre-pregnant patients should be changed to the newer preparations. Highly purified insulins cost little more than conventional insulins in the free market, and should be used in all newly diagnosed insulin-requiring diabetics. More recently, human insulin has become available through both DNA recombinant technology and amino acid substitution techniques. It has proved to have identical characteristics to pork insulin both in vitro and in normal subjects. Clinical trials with human insulin are at present in progress.