Current insulin regimens fall short of normal physiology thereby presenting the risk of hypoglycaemia

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The limitations of intermittent subcutaneous insulin delivery arise partly because insulin enters the systemic rather than the portal circulation. The inability to deliver the insulin directly to the liver, as happens when insulin is secreted from the b-cells, causes higher insulin levels in the peripheral circulation. In addition, short-acting insulin preparations tend to self-associate into hexamers, delaying the rate of absorption of insulin into the bloodstream from subcutaneous depots. Different approaches have been tried to develop a basal insulin preparation, i.e. that mimics normal background low-level insulin secretion, that has stable and consistent characteristics. However, lente and isophane preparations not only produce an undesirable peak of insulin but have considerable inter- and intra-subject variability.

Recently introduced rapid-acting and so-called basal insulin analogues have improved pharmacokinetics that may prove more useful than conventional insulin preparations. To date, clinical trial data indicate that these novel analogues provide a relatively modest albeit useful advance with reduced rates of hypoglycaemia at similar levels of glycaemic control. Clinicians - and patients -need to gain more experience with these analogues in order to determine their optimal application. As for conventional insulin, the particular circumstances of the patient will require careful individualisation of therapy to attain glycaemic targets safely.

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