Elsevier Saunders

0031-3955/05/$ - see front matter © 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.pcl.2005.07.010 pediatric.theclinics.com

(eg, insulin resistance of puberty) and psychosocial (eg, adolescent noncompliance, eating disorders) factors [10,13,14]. Although potential novel therapies for T1D are being developed (eg, islet transplantation, artificial endocrine pancreas), insulin replacement by injection remains the cornerstone of treatment [15]. For the moment, better outcomes for children and teens who have T1D depend in large part on the ability to more appropriately tailor the insulin regimen for each individual. This article reviews the advantages to and caveats of the use of newer insulin formulations (insulin analogues) and regimens in children and teens who have T1D, their affect on glycemic control, frequency of hypoglycemic events, daily insulin requirements, and adverse affects such as excessive weight gain, which provides a further major challenge in adolescents. We also address briefly the use of adjunctive agents in the treatment of T1D in children and teens.

Development of insulin formulations

Since the discovery of insulin by Banting and Best at the University of Toronto in 1921, there have been important advances in insulin therapy. The first commercial preparations isolated and purified insulin from porcine and bovine pancreata. They were relatively cheap and readily available in many parts of the world. Although not necessarily inferior in clinical efficacy, these preparations had greater immunogenicity, which was believed to alter their pharmacodynamics by the presence of high titer anti-insulin antibodies acting as insulin-binding proteins [16].

In the early 1980s, first purified pork insulin and soon thereafter insulin produced by recombinant DNA technology became available, which dramatically reduced the immune effects (eg, antibody production, insulin allergy, and lipoatrophy) of the porcine and beef products. The production of biosynthetic human insulin largely eliminated the need for animal pancreata in the production process. The pharmacokinetic and pharmacodynamic properties of biosynthetic human insulins were not sufficiently different from those of animal-derived insulins to allow major improvements in the ability to achieve and maintain glycemic control in individuals who have T1D [17]. Over the past 10 years or so, recombinant DNA technology has been used to produce modified human insulins, which are insulin analogues with—at least theoretically—improved pharmacokinetic features. These insulins include rapid-acting and very long-acting analogues.

The ultimate goal of exogenous insulin therapy is to mimic endogenous insulin secretion, which is characterized by continuous basal and meal-related acute increases in insulin secretion [18,19]. Bolus insulins aim to match the meal-related or prandial increases in blood glucose and include short-acting insulins and rapid-acting insulin analogues, both of which have a relatively fast onset and short duration of action. The basal insulins are the intermediate-acting, long-acting insulins and the very long-acting analogues, which have a slower onset and a longer duration of action and are used to suppress lipolysis and hepatic glucose

Table 1

Pharmcodynamics of subcutaneous injections of insulin types*

Insulin type

Action characteristics (h)

Appearance

Onset

Peak

Duration

Rapid-acting analogues Clear insulin lispro insulin aspart Fast-acting insulins Clear humulin regular soluble insulin Intermediate-acting insulins Cloudy isophane or NPH lente

Long-acting insulin Cloudy ultralente

Very long-acting analogues Clear detemir glargine

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