Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

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.

Direct epitaxial growth of θ-Ni2Si by reaction of a thin Ni(10 at.% Pt) film with Si(1 0 0) substrate

The reaction between an 11 nm Ni(10 at.% Pt) film on a Si substrate has been examined by in situ X-ray diffraction (XRD), atom probe tomography (APT) and transmission electron microscopy (TEM). In situ XRD experiments show the unusual formation of a phase without an XRD peak through consumption of the metal. According to APT, this phase has an Si concentration gradient in accordance with the θ-Ni2Si metastable phase. TEM analysis confirms the direct formation of θ-Ni2Si in epitaxy on Si(1 0 0) with two variants of the epitaxial relationship. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.