Treatment with insulin glargine reduces asymptomatic hypoglycemia detected by continuous subcutaneous glucose monitoring in children and adolescents with type 1 diabetes.

OBJECTIVE: Unsatisfactory basal insulin substitution may lead to asymptomatic hypoglycemia in children and adolescents with type 1 diabetes (T1D). To investigate the effects of multiple daily injections before and after changing to insulin glargine (IG), continuous glucose monitoring system (CGMS) data were used to analyze glycemic control and hypoglycemic episodes during the two different therapy regimens. METHODS: Basal insulin therapy was changed to one daily injection of IG in 30 pediatric patients with T1D (14 boys and 16 girls; age 4.5-18.3 yr, median 14.2 yr; diabetes duration 0.5-15.6 yr, median 4.6 yr) having elevated fasting glucose or recurrent hypoglycemia despite treatment with multiple injection therapy (basal insulin: two to four injections of neutral protamine Hagedorn (NPH) and/or zinc lente insulin). Ambulatory CGMS was applied before and 6-8 wk after treatment change. Frequency of hypoglycemic and hyperglycemic episodes, glucose area under the curve (AUC), and time below 60 mg/dL and above 180 mg/dL, respectively, were calculated from CGMS data during the day (8:00-22:00 hours) and at night (22:00-8:00 hours). RESULTS: Nocturnal hypoglycemia was detected by CGMS in 20 patients before and in 12 patients after the change to IG (p = .039), whereas both, the number of nocturnal and diurnal hypoglycemic episodes, decreased not significantly from 41 to 36 (p = .758) and 48 to 28 (p = .055), respectively. AUC and time below 60 mg/dL as well as hemoglobin A1c (HbA1c) were not significantly different before and after the change to IG. CONCLUSION: Under treatment with IG, asymptomatic hypoglycemia was reduced without increase of HbA1c.

Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes.

OBJECTIVE: This trial aimed to characterize for the first time the pharmacokinetic profile of insulin detemir, the novel soluble basal insulin analog, in children and adolescents compared with adults. Comparisons were also made with NPH insulin to determine any between-treatment difference in the effect of age on pharmacokinetic profile. RESEARCH DESIGN AND METHODS: This single-center, open-label, randomized, crossover trial included children (aged 6-12 years, n = 13), adolescents (aged 13-17 years, n = 10), and adults (aged 18-65 years, n = 11) of both sexes. Subjects were given single doses of 0.5 units/kg s.c. insulin detemir or 0.5 IU/kg NPH insulin on 2 separate days. Serial blood sampling was performed for 24 h for analysis of serum insulin detemir, human insulin, and glucose concentrations. RESULTS: The mean pharmacokinetic profile of insulin detemir was similar across all three age-groups. This was determined by statistical analyses of the data, which showed no overall age effect or between-group differences when pairwise comparisons were made between children (or adolescents) and adults on the parameters of the area under the curve (AUC), AUC from zero to infinity, AUC from 0 to 24 h [AUC((0-24 h))], and the maximum concentration measured during the 24 h after closing. No overall age effect for AUC((0-24 h)) and C(max) was detected for NPH insulin, but data were only analyzable from seven adults and pairwise comparisons did indicate that children and adults had different pharmacokinetic profiles. Less total variability in the pharmacokinetics of insulin detemir than NPH insulin was indicated by lower coefficients of variation in AUC, C(max), and time to maximum concentration in all three age-groups. CONCLUSIONS: The data suggest that insulin detemir can be used in children and adolescents with type 1 diabetes using titration guidelines similar to those used in adults. Moreover, insulin detemir may offer the advantage of greater predictability of response in comparison to NPH insulin due to lower total variability and a lesser degree of kinetic disparity across age-groups.