OBJECTIVE -The aim of this study was to compare the glycemic control of preprandial versus postprandial injections of the new rapid-acting insulin analogue aspart in children and adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODS -Forty-two children (aged 6 -12 years) and 34 adolescents (13-17 years) were randomized to preprandial (immediately before meal start) and postprandial (immediately after a meal or a maximum of 30 min after meal start) treatment with insulin aspart (at least thrice daily) as part of a basal/bolus regimen in a multicenter study with an open labeled, two-period cross-over design (6-week periods). Of this group, 49% were boys, 55% were aged Յ13 years, and duration of diabetes was 4.4 years (range 1.0 -9.4).RESULTS -Glycemic control for postprandial treatment was not worse than preprandial treatment as assessed by fructosamine week 0 vs. 6 (mean Ϯ SD, preprandial 367 Ϯ 74 vs. 378 Ϯ 90 mol/l; postprandial 383 Ϯ 83 vs. 385 Ϯ 77 mol/l) and HbA 1c (preprandial 7.9 Ϯ 1.3 vs. 8.0 Ϯ 1.5%; postprandial 8.0 Ϯ 1.4 vs. 8.3 Ϯ 1.5%, P ϭ 0.14). The only statistically significant finding from the seven-point blood glucose profiles and derived parameters between preprandial and postprandial treatment was a lower postprandial glucose level 120 min after breakfast (mean Ϯ SEM, Ϫ2.08 Ϯ 0.74 mmol/l, P ϭ 0.016). The relative risk of hypoglycemia (blood glucose Ͻ3.9 mmol/l) preprandially to postprandially was not significantly different (mean 1.1; 95% CI 0.91-1.35; P ϭ 0.31). Overall treatment satisfaction was equally high for both regimens with both patients and parents.CONCLUSIONS -Although preprandial administration of insulin aspart is generally preferable, this study shows that in children and adolescents, postprandial administration of insulin aspart is a safe and effective alternative.
The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid-acting insulin analogues during intensive insulin therapy.
The uptake and retention in a 2 cm thick brain section was recorded serially by SPECT after i.v. injection of [99mTc]-d,l-HM-PAO (HM-PAO). In 16 patients, the fraction of the administered dose retained by the brain was 5.2 +/- 1%, showing a peak after 40-50s, then decreasing by 10% within the first 10 min and then by only 0.4% per hour. The image contrast was measured in each patient as the regional hemispheric asymmetry difference in percent of the highest value of the two regions. It decreased from 31% at 30-40 s to 25% at 10 min. At 24 h, a value of 19% was reached. Using the images obtained at 10 min after injection, a region to region comparison of the original and corrected HM-PAO images to the xenon-133 regional cerebral blood flow (rCBF) images was performed. Forty-four patients with stroke, epilepsy, dementia, basal ganglia disease, and tumors and control subjects were included in this comparison. The algorithm proposed by Lassen et al. was used to correct the original images for back diffusion of tracer (brain to blood); a good correlation very close to the line of identity between the corrected HM-PAO and xenon-133 data was obtained when using a conversion/clearance ratio of 1.5 and when the noninvolved hemisphere was used as a reference region (r = 0.86, p less than 0.0001). Serial arterial and cerebral venous blood sampling was performed over 10 min following i.v. injection of HM-PAO in six patients. An overall brain retention fraction of 0.37 +/- 0.03 (mean +/- SEM) was calculated from the data. An average CBF of 0.62 +/- 0.12 ml/g/min was determined on the basis of the Fick principle; this compared to a value of 0.59 +/- 0.09 ml/g/min (mean +/- SEM) measured by the xenon-133 inhalation method. The two sets of CBF values correlated linearly with a correlation coefficient of 0.97 (p less than 0.01). Inserting the average CBF value for the hemisphere as measured by the Fick principle into the algorithm described by Lassen et al. yields absolute rCBF values (ml/g/min) directly from the corrected HM-PAO images.(ABSTRACT TRUNCATED AT 400 WORDS)
This trial confirmed that a thrice-daily BIAsp regimen can safely be used to intensify treatment for patients inadequately controlled on twice-daily BHI. A treat-to-target trial is required to explore the full potential of the BIAsp regimens and evaluate their use as a viable alternative to intensification with a basal-bolus regimen.
Summary:The initial extraction (E) across the blood brain barrier (BBB) of [99mTc]-d,I-HM-PAO after intra carotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as the cotracer. In both series, cere bral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 ILl), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p < 0.001): With a small bolus of saline and at resting CBF (0.75 mUg/min), E was 0.81, decreasing to 0.56 at a high CBF (1.5 ml/g/min). The calculated permeability surface area product (PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p < 0.01).E was found to increase when the bolus volume of saline d,l-Hexamethylpropyleneamine oxime (d,l HM-PAO) chelated with technetium-99m has been developed as a tracer for measuring regional cere bral blood flow (rCBF) distribution in humans (Neirinckx et aI., 1987; Sharp et aI., 1985). The complex e9mTc-d,I-HM-PAO) is lipophilic and dif fuses across cell membranes including the blood brain barrier (BBB) and can thus enter the brain. With a molecular weight of 384 and an octanol water partition coefficient of 80 (Andersen et aI., 1988) , it could be expected that the initial uptake is close to 100% (Hansch et aI., 1967; Fenstermacher et aI., 1984; Dischino et aI., 1983; Levin et aI., 1980). However, is the exchange of d,l-HM-PAO across the BBB sufficiently rapid at all flow levels so as to Address correspondence and reprint requests to Dr. A. R. Andersen at Department of Neurology, N2081, Rigshospitalet, Blegdamsvej DK-2100, Copenhagen, Denmark. S44was increased from 20 to 120 ILl, while using a 120 ILl bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood ele ments may reduce the apparent extraction across brain capillaries. In patients using a bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p < make the initial tracer uptake solely dependent on blood flow?In order to investigate some of the relevant phys iological properties of d,l-HM-PAO, we have mea sured the initial fractional uptake, the apparent ex traction (E) across the BBB, as a function of CBF in rats and in humans using the double indicator, sin gle injection method (Chinard et aI., 1955;Crone, 1963;Hertz and Paulson, 1983). With this method, the venous outflow concentrations of a diffusable test substance and of an impermeable reference substance indicate the extent of trans capillary loss that has occurred during a single passage following an intra-arterial injection of the tracers. The method also allows us to gain a qualitative assessment of HM-PAO backdiffusion (brain to blood) during the short experimental period. This phenomenon is well known for i...
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