Efficacy and safety of switching to insulin glulisine from other rapid-acting insulin analogs in children with type 1 diabetes.

We investigated the efficacy and safety of switching to insulin glulisine (GLU) from other rapid-acting insulin analogs (Ra) in children with type 1 diabetes treated with multiple daily injections of insulin or continuous subcutaneous insulin infusion. A total of 26 children with type 1 diabetes were included. Ra in all of these patients was changed to GLU, and they were observed for a 6-month period after having previously finished treatment with other Ra. The mean glycated hemoglobin value decreased from 7.6 ± 1.0 to 7.4 ± 0.9% (P = 0.0034), and mean plasma glucose values after breakfast and supper also improved from 183 ± 50 to 153 ± 32 mg/dL (P = 0.0035), and from 203 ± 29 to 164 ± 23 mg/dL (P < 0.0001), respectively. Furthermore, the mean frequency of hypoglycemia was reduced from 7 ± 6 to 4 ± 4/month (P = 0.0004), while insulin doses and obesity degree were stable with statistically non-significant differences. In conclusion, switching to GLU might be a good treatment option for improving glycemic control in children with type 1 diabetes.

Three years of liraglutide treatment offers continuously optimal glycemic control in a pediatric patient with maturity-onset diabetes of the young type 3.

Sulfonylureas (SUs) are recommended as the first-line pharmacological treatment in patients with uncontrolled maturity-onset diabetes of the young type 3 (MODY3). In contrast, glucagon-like peptide-1 (GLP-1) receptor agonists have the advantages of a low risk of hypoglycemia and maintained ß-cell function. We report a pediatric patient with MODY3 treated with a GLP-1 receptor agonist, liraglutide. A 12-year-old Japanese girl with MODY3 had been treated with insulin for 6 months since the time of diagnosis. After genetic analysis, we switched her treatment from insulin to liraglutide. After switching to liraglutide, the patient maintained optimal glycemic control with hemoglobin A1c levels of 6.8%-7.5% and had postprandial C-peptide levels >3.0 ng/mL during a 3-year treatment period. No adverse events associated with liraglutide were observed. GLP-1 receptor agonists are the potential medications for patients with MODY3 who maintain residual insulin secretion.

Basal insulin requirement of youth with type 1 diabetes differs according to age.

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2-h postprandial C-peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.

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.

Clinical characteristics of non-obese children with type 2 diabetes mellitus without involvement of ß-cell autoimmunity.

AIMS: We examined the clinical characteristics of non-obese Japanese children with type 2 diabetes mellitus (T2DM) not associated with ß-cell autoimmunity. METHODS: Of 218 children who were diagnosed as having T2DM by a school urine glucose screening program in Tokyo, 24 were identified as being non-obese and were enrolled in this study. None of the children had any evidence of ß-cell autoimmunity or genetic disorders. RESULTS: The mean ages at diagnosis and at the study were 12.5 ± 1.7 and 22.4 ± 5.7 years, respectively. Females were predominant (M/F ratio: 4/20). Family history of T2DM, mostly of the non-obese type, was present in 62.5% of the cases. In regard to the birth weight, 20.8% had a history of low birth weight, and 8.3% were large for gestational age. The mean fasting insulin level, HOMA-R, HOMA-ß, and an insulinogenic index on the OGTT at the time of diagnosis were 11.8 ± 7.8 µU/ml, 5.4 ± 3.8, 96.1 ± 55.0 and 0.16 ± 0.14, respectively. Most patients were treated by either oral hypoglycemic drug (45.8%) or insulin (50.0%) therapy at the study, with the mean interval to the start of pharmacological treatment of 3.1 ± 2.3 years. CONCLUSIONS: Non-obese children with T2DM seemed to show lower insulin secretory capacities with mild, but evident, insulin resistance even from the time of diagnosis, and also earlier requirement of pharmacological therapies during the clinical course. Some genetic factors not associated with autoimmunity may play a role in the etiology of T2DM in non-obese children.

Insulin resistance at diagnosis in Japanese children with type 2 diabetes mellitus.

BACKGROUND: Insulin resistance at diagnosis was investigated in Japanese children with type 2 diabetes mellitus (T2DM). METHODS: A total of 160 children with T2DM were divided into groups on the basis of percent overweight at time of diagnosis: group A (n = 28), <20%; group B (n = 55), 20-39%; group C (n = 37), 40-59%; group D (n = 40), ≥ 60%. Indicators of insulin resistance at diagnosis were compared among the four patient groups, and also between the children with T2DM and the 201 age-matched normal Japanese children. RESULTS: There were no significant differences in plasma glucose (PG) levels among the four patient groups. The mean concentration of fasting plasma immunoreactive insulin (IRI) was significantly higher in group D than in groups A and B (39.2 µU/mL vs 16.2 µU/mL and 24.1 µU/mL, P < 0.05, respectively). The mean homeostasis model assessment (HOMA-R) was significantly higher in group D than in all the other three groups (17.6 vs 7.8, 10.8 and 12.7, P < 0.05, respectively). The indicators HOMA-R and fasting IRI were significantly higher in each diabetes group, even in non-obese group A, than in normal children (P < 0.01, respectively). CONCLUSIONS: Japanese children with T2DM had insulin resistance at diagnosis regardless of percent overweight, and the degree of insulin resistance gradually increased with rise in percent overweight.