IMPROVING INSULIN THERAPY - ACHIEVEMENTS AND CHALLENGES

Microvascular complications of diabetes can be forestalled by effectiv e glycemic control. However, the inherent limitations of standard subc utaneous insulins reduce their ability to control glycemia without ris k of significant hypoglycemia and hyperinsulinemia. Hypoglycemia is un acceptable for most patients and may be dangerous. Hyperinsulinemia is undesirable because it causes weight gain and it has a putative assoc iation with atherosclerosis. This paper summarizes the major historica l improvements in insulin therapy, and calls attention to the fact tha t none of the presently available commercial preparations in any combi nation is capable of simulating the profile of normal insulin secretio n - the latter being regarded as the most effective means of normalizi ng glycemia. For this reason, a variety of new approaches to simulatin g the pharmacokinetics or glucodynamics of insulin secretion are under investigation. Fast-acting insulin analogues suitable for subcutaneou s injection have been developed and appear to mimic the physiological insulin response more closely than standard insulins. Less progress ha s been made with basal insulins. Intravenous insulin has pharmacodynam ic advantages but practical disadvantages of administration. Nasal ins ulin would be an attractive treatment modality only if its bioavailabi lity could be significantly increased and its safety assured. Other in terventions which improve glucose metabolism without necessarily simul ating normal insulin secretion are under investigation. These include biosynthetic human C-peptide, insulin-like growth factor-1 and glucago n-like peptide 1 (7-36 amide).