Adverse effects of exogenous insulin. Clinical features, management and prevention

Insulin has been in therapeutic use for around 70 years, and the range of adverse effects associated with its use is very limited. Insulin allergy and other local cutaneous reactions, which were common with the early insulins, are now rarely seen with highly purified and biosynthetic preparations. By far the most important complication of exogenous insulin is hypoglycaemia, which affects almost all insulin-treated patients and is largely a manifestation of nonphysiological insulin regimens and routes of administration. The problem of hypoglycaemia unawareness is now being increasingly recognised, with onset of severe neuroglycopenia and coma which is not preceded by the characteristic warning symptoms associated with autonomic activation. This can occur with excessively tight glycaemic control, and this situation is usually reversible. More commonly, however, hypoglycaemia unawareness is a chronic problem which is predominantly a feature of long duration of diabetes. Although individual episodes of hypoglycaemic coma can usually be effectively treated with parenteral dextrose or glucagon, management of patients with chronic hypoglycaemia unawareness is a difficult clinical challenge, with limited therapeutic options. In the past few years, there has been concern that the use of human insulin preparations may predispose to hypoglycaemia unawareness. The evidence for and against this is discussed, although at present it is difficult to draw any absolutely firm conclusions.