What is the role of insulin in the treatment of pediatric type 1 diabetes mellitus (DM)?

Updated: Jul 03, 2019
  • Author: William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH; Chief Editor: Sasigarn A Bowden, MD  more...
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Answer

Insulin is always required to treat type 1 diabetes mellitus. Originally, all insulin was derived from the highly purified pancreatic extracts of pigs and cattle, and this form of insulin is still available. Human insulin was later manufactured using recombinant deoxyribonucleic acid (DNA) technology. "Designer" insulins are also now being produced; they are based on the human molecule and are tailored to meet specific pharmacologic targets, particularly duration of action. Insulin must be given parenterally, and this effectively means subcutaneous injection. [69]

Alternatives to injecting insulin have been constantly sought, including an inhaled form of insulin. Several products were in development, and one (Exubera) was licensed for use but failed to generate sufficient market penetration to justify continued production. The search for alternatives continues, including oral sprays, sublingual lozenges, and delayed-absorption capsules.

Insulin has 4 basic formulations: ultra ̶ short-acting (eg, lispro, aspart, glulisine), traditional short-acting (eg, regular, soluble), medium- or intermediate-acting (eg, isophane, lente, detemir), and long-acting (eg, ultralente, glargine).

Regular or soluble insulin is bound to either protamine (eg, isophane) or zinc (eg, lente, ultralente) in order to prolong the duration of action. Combinations of isophane and regular, lispro, or aspart insulins are also available in a limited number of concentrations that vary around the world, ranging from 25:75 mixtures (ie, 25% lispro, 90% isophane) to 50:50 mixtures. The following image illustrates the activity profile of various insulins.

Representation of activity profile of some availab Representation of activity profile of some available insulins.

The development of insulin analogues has attempted to address some of the shortcomings of traditional insulin. [70] Insulins lispro, glulisine, and aspart have a more rapid onset of action and shorter duration, making them more suitable for bolusing at mealtimes and for short-term correction of hyperglycemia. (See the graph below.) They are also more suitable for use with insulin pumps. An intermediate-acting insulin (detemir) has a similar profile of action to NPH but is more pharmacologically predictable and is less likely to cause weight gain, whereas glargine has a relatively flat profile of action, lasting some 18-26 hours. Despite their apparent advantages over traditional insulins, no evidence suggests a long-term advantage of the analogue insulins in terms of metabolic control or complication rates. [71]

Representation of activity profile of some availab Representation of activity profile of some available insulins.

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