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Use of new insulins in children
  1. Fiona M Regan,
  2. David B Dunger
  1. Department of Paediatrics, Addenbrooke’s Hospital, Cambridge, UK
  1. For correspondence:
    Professor David B Dunger
    Department of Paediatrics, Addenbrooke’s Hospital, Box 116 level 8, Hills Road, Cambridge, CB2 2QQ, UK; dbd25{at}cam.ac.uk

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Banting and Best extracted the first insulin to be used in a clinical setting from dogs’ pancreata in 1922. This was the advent of a remarkable medical breakthrough in the treatment of diabetes and Banting and Macleod were awarded the Nobel Prize for Medicine and Physiology in recognition of the significance of their achievement. The initial formulations contained many impurities and hence there was wide variability in potency from one batch to another. John Abel isolated insulin in its pure and crystalline form in 1926 and, alongside improved manufacturing techniques, this resulted in production of higher quality formulations from bovine and porcine sources. The 1930s saw the introduction of medium and long acting insulins, following the discovery, by Hagedorn, that addition of protamine to insulin preparations prolonged insulin action by slowing absorption. In 1964 Panavotis and Katsoyanis developed the first synthesised human insulin and recombinant DNA technology in the 1980s allowed manufacture of human insulin on a commercial scale. However, it was another 15 years before radically new insulin analogues were developed and licensed.

INSULIN ANALOGUES

Insulin analogues have been developed through genetic engineering of the native insulin molecule to try and overcome some of the hurdles faced when using regular human insulin for replacement.

The limitations of regular insulin include the necessity to inject 20–30 minutes before ingestion of food to allow for the delay in onset of action and the prolonged period of action of up to eight hours. This profile may result in high postprandial glucose while running the risk of pre-prandial hypoglycaemia. The limitations of the traditional long acting insulins relate to the pronounced peak of effect, rather than a smooth continuous action, an action profile of less than 24 hours, and pronounced intra- and inter-subject variation. Alteration of specific amino acid sequences, addition of amino acids and …

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