Remi Kuwabara

Efficacy and safety of switching from insulin glargine to insulin degludec in young people with type 1 diabetes

We evaluated the efficacy and safety of switching to insulin degludec (IDeg) from insulin glargine (IGlar) as basal-bolus therapy in young people with type 1 diabetes. The subjects were 36 patients, 21.3±1.0 years of age, with type 1 diabetes. IGlar had previously been injected once daily in 25 patients and twice daily in 11. They were then switched from IGlar to once-daily injection of IDeg. Both fasting plasma glucose (FPG) and HbA1c levels decreased significantly from 134±3.9 mg/dL and 7.9±0.2% at baseline to 116±2.2 mg/dL and 7.4±0.2% at 12 months after starting IDeg (P<0.0001 and P≤0.001, respectively). Overall and nocturnal hypoglycemia (PG<70 mg/dL) frequencies also decreased significantly from 4.9±0.7 and 2.0±0.3 times/month to 2.4±0.3 and 0.4±0.1 times/month at 12 months after starting IDeg (P≤0.005 and P<0.0005, respectively). The daily basal insulin dose was significantly reduced from 0.48±0.04 units/kg/day at baseline to 0.38±0.03 units/kg/day at the end of the study period (P<0.0001), which corresponded to 79.2% of the baseline value. Trends were similar in patients receiving the once-daily injection and those given twice-daily injections, but basal-insulin value reductions from baseline were more marked in patients receiving twice-daily injections of basal insulin (76.0% vs. 82.6% of the baseline value). These results suggest that switching from IGlar to an appropriate dose of IDeg may effectively control hyperglycemia while reducing the frequency of hypoglycemia episodes in young Japanese people with type 1 diabetes.

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

AIMS We examined the clinical characteristics of non-obese Japanese children with type 2 diabetes mellitus (T2DM) not associated with β-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 β-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-β, 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).

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.

“Metabolically Healthy” Obesity and Hyperuricemia Increase Risk for Hypertension and Diabetes: 5-year Japanese Cohort Study

Whether obesity without metabolic syndrome (i.e., “metabolically healthy” obesity) confers similar or less metabolic risk remains controversial.

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.

Changes in annual incidence of school children with type 2 diabetes in the Tokyo Metropolitan Area during 1975-2015

To analyze changes in the annual incidence of school students with type 2 diabetes detected by urine glucose screening at schools in the Tokyo Metropolitan Area during 1975‐2015.

Different Risk for Hypertension, Diabetes, Dyslipidemia, and Hyperuricemia According to Level of Body Mass Index in Japanese and American Subjects

Obesity is a risk factor for hypertension, diabetes mellitus (DM), dyslipidemia, and hyperuricemia. Here, we evaluated whether the same body mass index (BMI) for the U.S. population conferred similar metabolic risk in Japan. This was a cross-sectional analysis involving 90,047 Japanese adults (18–85 years) from St. Luke’s International Hospital, Tokyo, Japan and 14,734 adults from National Health and Nutrition Examination Survey (NHANES) collected in the U.S. We compared the prevalence of hypertension, DM, dyslipidemia, and hyperuricemia according to BMI in Japan and the U.S. The prevalence of hypertension, DM, and dyslipidemia were significantly higher in the U.S. than Japan, whereas the prevalence of hyperuricemia did not differ between countries. Higher BMI was an independent risk factor for hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and in the U.S. after adjusting for age, sex, smoking and drinking habits, chronic kidney disease, and other cardiovascular risk factors. The BMI cut-off above which the prevalence of these cardio-metabolic risk factors increased was significantly higher in the U.S. than in Japan (27 vs. 23 kg/m2 for hypertension, 29 vs. 23 kg/m2 for DM, 26 vs. 22 kg/m2 for dyslipidemia, and 27 vs. 23 kg/m2 for hyperuricemia). Higher BMI is associated with an increased prevalence of hypertension, DM, dyslipidemia, and hyperuricemia both in Japan and U.S. The BMI cut-off above which the prevalence of cardio-metabolic risk factors increases is significantly lower in Japan than the U.S., suggesting that the same definition of overweight/obesity may not be similarly applicable in both countries.

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.