Usefulness of insulin detemir in Japanese children with type 1 diabetes.

BACKGROUND: This multicenter observational study was conducted to investigate the efficacy and safety of insulin detemir (detemir) for diabetes management in Japanese children and adolescents. METHODS: Data from the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes database were analyzed. Ninety children (32 boys, 58 girls; mean age, 11.9 ± 3.8 years) who transferred from a neutral protamine Hagedorn insulin or insulin glargine basal-bolus regimen to detemir basal-bolus therapy and who were observed for at least 12 months were identified. Clinical data obtained at 0, 3, 6, and 12 months were analyzed to determine the type of bolus insulin used, number and timing of detemir injections, detemir dose as a proportion of the total insulin dose, hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and frequency of severe hypoglycemia. RESULTS: Twelve months after switching to detemir, the detemir dose represented 39.8% of the total insulin dose, and 37.8% of patients were being treated with twice-daily injections. HbA1c and FBG were significantly reduced from baseline at 3 and 6 months but not at 12 months. Considering the seasonal HbA1c variation in the Japanese population, a separate analysis was performed using data for 65 children (21 boys, 44 girls; mean age, 11.6 ± 2.9 years) who switched to detemir during the winter. Subset analysis showed significant HbA1c reductions from baseline at all specified times. The incidence of severe hypoglycemia during detemir treatment was 4.4 episodes per 100 patient-years. CONCLUSIONS: Detemir is an effective and safe basal insulin for diabetes management in Japanese children and adolescents.

Microscope-assisted reduction clitoroplasty used to treat two patients with clitoromegaly.

We report 2 cases of clitoromegaly, 1 in a patient with true hermaphroditism, and the other in a patient with adrenogenital syndrome. Both were treated surgically with reduction clitoroplasty. There are 3 different clitoroplasty procedures: clitorectomy, clitoral recession, and reduction clitoroplasty. Reduction clitoroplasty with preservation of the neurovascular bundle is considered superior in terms of formation of the external genitals and sensation. However, the disadvantages are that detachment of the neurovascular bundle from the clitoral shaft is difficult and that there is a high possibility of sensory and blood flow disorders in the clitoris. In an attempt to achieve safe and reliable surgical manipulation, we used a surgical microscope (OPMI 6-SDFC, Carl Zeiss Surgical GmbH, magnification x8) to detach the neurovascular bundle from the clitoral shaft in our 2 patients. Our impression is that our efforts were extremely effective. Furthermore, our experience leads us to believe that the procedure for neurovascular bundle detachment required in reduction clitoroplasty is not particularly difficult if performed with a surgical microscope by a plastic surgeon who regularly performs microsurgery. Because the procedure can be performed simply and safely, we believe that reduction clitoroplasty with preservation of the neurovascular bundle is the best overall of the 3 clitoroplasty procedures.

Three-Year Follow-up Study on Serum Leptin Levels in GH Deficient Children with GH Replacement Therapy.

Interactions between GH and leptin have been extensively studied. However, results of long-term GH therapy on serum leptin levels in GH-deficient children were not consistent. Moreover, no such reports were available in Japanese children with this disease. We studied 35 Japanese patients with GH deficiency (26 boys and 9 girls, mean age: 9.8 ± 6.2 yr old), of whom 6 patients with complete and 29 with incomplete GH deficiency were identified by GH provocation test. Serum leptin levels, percent of ideal body weight (%IBW) and percent fat (%fat) were determined at 0, 1, 3, 6, 12, 18, 24, and 36 mo after beginning GH therapy. Baseline levels of %fat and leptin were significantly higher in girls than boys (P<0.05), though serum leptin did not change throughout the study period in either group. Further, %IBW did not change significantly, whereas %fat exhibited significant changes after 6 mo in boys and remained virtually constant thereafter for up to 3 yr. In summary, serum leptin levels did not change in GH-deficient boys and girls during the 3-yr period after the start of GH replacement therapy, despite a decrease in %fat after 6 mo of therapy in the boys. Thus, it is conceivable that long-term GH replacement therapy can be employed without an effect on normal leptin secretion.

The factors affecting glycemic control in Japanese adolescents with type 2 diabetes mellitus.

The factors affecting glycemic control were examined using HbA(1C) as an index in a total of 22 patients with type 2 diabetes mellitus whose ages at onset were less than 18 years old. As a result, the presence or absence of the following cases were considered possible factors for significant exacerbation of glycemic control: diabetic microangiopathy; school phobia or nonworking situation; drug therapy; use of more than two kinds of oral hypoglycemic agents (OHAs) or insulin for the drug therapy cases. No improvement in glycemic control could be achieved even by increasing the number of OHAs for co-administration or by insulin use unless dietary/exercise therapy, a basic therapeutic option, was adequately performed.

Indexes of insulin resistance using the oral glucose tolerance test (O-GTT) in Japanese children and adolescents.

An oral glucose tolerance test (O-GTT) was conducted in 96 non-obese healthy children (7 to approximately 11 years old) and adolescents (12 to approximately 16 years old) to obtain the index of insulin resistance from the insulin (IRI) and C-peptide (CPR) values of fasting. 2-hour postload conditions and the sigma values, and the homeostasis model assessment ratio (HOMA-R) by assuming the value of the mean + 2SD to be the upper limit of the normal value for each clinical variable. The results show that the adolescents, whose insulin resistance is thought to increase, showed higher IRI and CPR values of the 2-hour postload condition and sigma values compared to those of the children, but there were no differences between the 2 age groups in the values of the fasting condition, as well as in the HOMA-R values which were calculated from the fasting values. These findings indicate that there is a limitation in using fasting values to judge insulin resistance. Instead, using the 2-hour postload values and/or the sigma values is more appropriate.

Insulin resistance in Japanese adolescents with type 2 diabetes mellitus.

An oral glucose tolerance test (O-GTT) was conducted in 22 patients with type 2 diabetes mellitus whose ages at onset were less than 18 years old. They were classified into 2 groups, obese and non-obese at onset, and insulin secretory function was compared with that of a non-obese healthy group. The results show that, in the group of obese subjects with type 2 diabetes mellitus, both values of fasting IRI and sigmaIRI were significantly higher than those in the healthy group. In the non-obese adolescent group with type 2 diabetes mellitus, both values of fasting IRI and sigmaIRI were also significantly higher than those in the healthy group, although the difference was not as prominent as in the obese subjects with type 2 diabetes mellitus. It was revealed that insulin resistance is present not only in obese adolescents with type 2 diabetes mellitus, but also in non-obese adolescents with type 2 diabetes mellitus.