Ayako Yoshida

Incidence of children with slowly progressive form of type 1 diabetes detected by the urine glucose screening at schools in the Tokyo Metropolitan Area

We investigated the incidence of the slowly progressive form of type 1 diabetes (SPT1D) detected by the urine glucose-screening tests at schools in the Tokyo Metropolitan Area from 1974 to 2004. During this study period, a total of 9,242,259 school students underwent the screening program. Of them, 54 children, 19 males and 35 females, aged 11.6+/-2.4 years, were diagnosed to have SPT1D by this method. The overall incidence of SPT1D was 0.57/100,000/year, which was about one fifth of that of type 2 diabetes detected by the same method. The incidence was significantly higher in junior high school students than in primary school students (0.32 vs. 1.13/100,000/year, p<0.0001). SPT1D accounts for one third of all pediatric cases of type 1 diabetes in Japan, showing that this clinical form is not rare in Japan. There were no significant changes in the incidence of SPT1D during the study period. The incidence of type 1 diabetes in Japanese children is quite low in comparison with Caucasian populations. This incidence, regardless of the clinical form of the disease, does not seem to be influenced by environmental factors in contrast with that of type 2 diabetes.

Differences in prevalence of antibodies to GAD and IA-2 and their titers at diagnosis in children with slowly and rapidly progressive forms of type 1 diabetes

We compared the frequencies of antibodies to GAD (GADA) and IA-2 (IA-2A) and their titers at diagnosis in 48 Japanese children with slowly progressive form of type 1 diabetes (SPT1D) and 70 children with rapidly progressive form of type 1 diabetes (RPT1D). High prevalences of both GADA and IA-2A were found at diagnosis in both the patients with SPT1D (70.8% and 75.0%), and those with RPT1D (71.4% and 71.9%). Most patients, regardless of the form of type 1 diabetes, were positive for both antibodies, though 6 of the 9 patients less than 5 years of age were negative for both antibodies. GADA titers below 50 U/ml were significantly more frequent in the patients with SPT1D (79.4% vs. 38.0%, p=0.0002), and titers above 100 U/ml significantly more frequent in those with RPT1D (38.0% vs. 11.8%, p=0.0081). No significant association was noted between the titers of IA-2A and the clinical form of type 1 diabetes. These results suggest that low GADA titers may reflect mild autoimmune destruction of beta-cells with slow disease progression. Titers of IA-2A do not appear to reflect the degree of autoimmune damage of the beta-cells.

Influence of plasma glucagon levels on glycemic control in children with type 1 diabetes.

Objective:  The aim of this study was to investigate the association between plasma glucose (PG), HbA1c and plasma glucagons levels in children with type 1 diabetes to determine the influence of plasma glucagon on their glycemic control.

Association between Sex, Age, Insulin Regimens and Glycemic Control in Children and Adolescents with Type 1 Diabetes

We examined the association between sex, age, insulin regimens and glycemic control in 133 Japanese children and adolescents, 42 males and 61 females aged 16.8 ± 7.0 yr, with type 1 diabetes mellitus (T1DM). The patients were divided into 5 age groups and were also classified according to the insulin regimen. The annual median HbA1c level in males (7.3 ± 0.2%) was similar to that in females (7.2 ± 0.2%). In regard to the age of the patients, the median HbA1c levels in patients aged 15–19 yr (7.9 ± 0.4%) was significantly higher than those aged 5–9 yr (7.2 ± 0.1%) and those aged 20≤ yr (6.6 ± 0.4%, p<0.05, respectively). On the other hand, there were no significant relationships between the HbA1c values and the insulin regimens. In conclusion, difficulty in management of diabetes due to emotional issues and endocrinological factors during adolescence may play a possible role in the deterioration of diabetes control. On the other hand, the insulin regimen does not seem to have a major impact on the metabolic outcome in young people with T1DM.

Prevalence of components of the metabolic syndrome in schoolchildren with newly diagnosed type 2 diabetes mellitus

Objective: To examine the prevalence of components of the metabolic syndrome (MS) other than hyperglycemia at diagnosis in schoolchildren with type 2 diabetes mellitus (T2DM).

Diabetes caused by Kir6.2 mutation: Successful treatment with oral glibenclamide switched from continuous subcutaneous insulin infusion in the early phase of the disease

Neonatal diabetes mellitus (NDM) is very rare, with an estimated incidence of one in 500 000 neonates. Its etiology and long-term clinical course are not well known. In most cases, blood glucose levels during the neonatal and infantile periods are controlled by insulin treatment. Diabetes mellitus (DM) diagnosed before 6 months of age, classified as NDM, frequently results from mutations of the KCNJ11 gene that encodes the Kir6.2 subunit of the adenosine triphosphate (ATP)-sensitive potassium channel (KATP channel). These are activating mutations, resulting in hyperpolarization of the cell membrane, and, in the case of the pancreatic b-cells, inhibition of insulin secretion. Notably, it has been reported that in these patients, treatment with a sulfonylurea (SU), which binds to the sulfonylurea receptor 1 (SUR1) subunit and closes the KATP channel, can stimulate insulin secretion and improve blood glucose control. We report a case of NDM caused by the Kir6.2 mutation (R201C) in a young infant, in whom treatment initiated with continuous subcutaneous insulin infusion (CSII) could subsequently be switched successfully to oral sulfonylurea treatment with glibenclamide.

Autoimmune characteristics in Japanese children diagnosed with type 1 diabetes before 5 years of age

Background:  Several studies have shown that the autoimmune features in young children with type 1 diabetes differ from those in older pediatric patients as well as adults. The purpose of the present study was to examine the prevalence of β‐cell autoantibodies, glutamic acid decarboxylase antibodies (GADA), and antibodies to the protein tyrosine phosphatase‐related molecule IA‐2 (IA‐2A), at the time of diagnosis in Japanese children with type 1 diabetes who were younger than 5 years at diagnosis.

Pharmacologic treatment strategies in children with type 2 diabetes mellitus.

We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics.

Utility of an Increment in the Basal Rate during Mealtime in Place of Pre-meal Boluses for Preschool-aged Children with Type 1 Diabetes Using CSII

In recent years, continuous subcutaneous insulin infusion (CSII) using a rapid-acting insulin analog (Ra) has increasingly been utilized for young children with type 1 diabetes mellitus (T1DM). Blood glucose levels are highly variable, and achieving adequate diabetes control is quite difficult for this age group with T1DM. Studies have demonstrated CSII using Ra to be useful for improving glycemic control and making insulin delivery more convenient (1,2,3,4,5,6). This treatment option seems more suited than any other insulin regimen for young children with T1DM. Recent insulin pumps used for CSII allow programming of various basal insulin rates at different times of day to accommodate changes in the required insulin level. Nevertheless, the children themselves or their parents need to push a button to administer insulin boluses before each meal. Accordingly, administration of the boluses is very difficult for children attending a kindergarten or day nursery because neither kindergarten teachers nor nurses can give the boluses in place of a child’s parents. Therefore, we introduced an increment in the insulin basal rate during a one-hour mealtime in place of pre-meal boluses in 4 preschoolers with T1DM using CSII.

Frequency of dawn phenomenon and its associations with age, HbA1c and diabetes duration in Japanese type 1 diabetes mellitus (T1DM) using the continuous glucose monitoring system (CGMS)

compared in terms of diabetes duration (13.0 ± 9.9 vs 10.0 ± 9.7: p<0.01)yr , HbA1c(8.3 ± 1.6 vs 8.5 ± 2.4: p<0.01)%, age at the time of the study (24.6 ± 18.0 vs 20.5 ± 14.9: p<0.01)yr. The subjects with dawn phenomenon had longer diabetes duration, lower HbA1c and were older. Furthermore, these subjects experienced hypoglycemia (< 70mg/dl) during the daytime. Conclusion The frequency of dawn phenomenon in the present study was lower than that in the previous studies .This might be attributable to there being many users of CSII amongour subjects and to Japanese foodscontaining a large amount of the carbohydrate as compared with protein. The associations of dawn phenomenon with longer diabetes duration and advanced age may be based on poor glycemic control. Furthermore, excess bolusescause hypoglycemia and low HbA1c.These results suggest that change in the basal insulin rate should be considered instead of an increase in the pre-meal bolus. We conclude that CGM should be used to adjust CSII.