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.

Liquid crystal based continuous phase retarder: From optically neutral to a quarter waveplate in 200 microseconds

Liquid crystal variable phase retarders have been incorporated into prototype devices for optical communications system applications, both as endless polarization controllers 1,2,3, and as holographic beam steerers 4. Nematic liquid crystals allow continuous control of the degree of retardation induced at relatively slow switching speeds, while ferroelectric liquid crystal based devices allow fast (sub millisecond) switching, but only between two bistable states. The flexoelectro-optic effect 5,6 in short-pitch chiral nematic liquid crystals allows both fast switching of the optic axis and continuous, electric field dependent control of the degree of rotation of the optic axis. A novel geometry for the flexoelectro-optic effect is presented here, in which the helical axis of the chiral nematic is perpendicular to the cell walls (grandjean texture) and the electric field is applied in the plane of the cell. This facilitates deflection of the optic axis of the uniaxial negatively birefringent material from lying along the direction of propagation to having some component in the polarization plane of the light. The device is therefore optically neutral at zero field for telecommunications wavelengths (1550nm), and allows a continuously variable degree of phase excursion to be induced, up to 2π/3 radians achieved so far in a 40μm thick cell. The retardation has been shown both to appear, on application of the field, and disappear on removal, at speeds of 100-500 μs. The direction of deflection of the optic axis is also dependent on the direction of the field, allowing the possibility, in a converging electrode "cartwheel cell", of endless rotation of the liquid crystal waveplate at a higher rate than achievable through dielectric coupling to plain nematic materials.