Standard or 'traditional' human
insulin preparations such as regular
soluble insulin and neutral
protamine Hagedorn (
NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified
insulin molecules or
insulin 'analogs' have been developed with the aim of delivering
insulin replacement
therapy in a more physiological manner. In the last 10 years, five
insulin analog preparations have become commercially available for clinical use in patients with
type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (
insulin lispro, aspart, and glulisine) and two long-acting analogs (
insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new
insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with
type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible
insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with
type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal
hypoglycemia, better postprandial
blood glucose control, and improved quality of life when compared with traditional
insulins. In addition,
insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in
glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to
insulin/
insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that
insulin analogs may have an increased mitogenic potential and risk of
tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of
insulin analog
therapy in children and adolescents with
type 1 diabetes.