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Type 1 diabetes (T1D) incidence varies substantially between countries/ territories, with most studies indicating increasing incidence. In Western Pacific region (WPR), reported rates are much lower than European-origin populations. In contrast, there are reports of substantial numbers of young people with type 2 diabetes (T2D). A deeper understanding of T1D and T2D in the WPR may illuminate factors important in pathogenesis of these conditions. Furthermore, with varying resources and funding for diabetes treatment in this region, there is a need to more clearly determine the current burden of disease and also any gaps in knowledge.To compile and summarise published epidemiologic and phenotypic data on childhood diabetes in non-European populations in and from WPR.Research articles were systematically searched from PubMed (MEDLINE), Embase, Cochrane library, and gray literature. Primary outcome measures were incidence and prevalence, with secondary measures including phenotypic descriptions of diabetes, including diabetes type categorization, presence of diabetic ketoacidosis (DKA) at onset, autoantibody positivity, C-peptide levels, and human leucocyte antigen phenotype. Extracted data were collected using a customized template. Three hundred and thirty relevant records were identified from 16 countries/territories, with analysis conducted on 265 (80.3%) records published from the year 2000.T1D incidence ranged from1-7.3/100000 individuals/year, rates were highest in emigrant/ mixed populations and lowest in South-East Asia, with most countries/territories (71.4%) having no data since 1999. Incidence was increasing in all six countries/territories with data (annual increases 0.5%-14.2%, highest in China). Peak age-of-onset was 10-14 years, with a female case excess. Rate of DKA at onset varied from 19.3%-70%. Pancreatic autoantibodies at diagnosis were similar to European-origin populations, with glutamic acid decarboxylase-65 autoantibody frequency of 44.1%-64.5%, insulinoma-associated 2 autoantibody 43.5%-70.7%, and zinc transporter-8 autoantibody frequency 54.3% (one study). Fulminant T1D also occurs. T2D was not uncommon, with incidence in Japan and one Chinese study exceeding T1D rates. Monogenic forms also occurred in a number of countries.T1D is less common, but generally has a classic phenotype. Some countries/ territories have rapidly increasing incidence. T2D is relatively common. Registries and studies are needed to fill many information gaps.

Continuous glucose monitoring (CGM) has been widely used in children and adolescents as well as adults with type 1 diabetes. CGM metrics include three key measurements of target glucose: time in range (TIR: 70-180 mg/dL), time below range (TBR:70 mg/dL), and time above range (TAR:180 mg/dL). The primary goal of optimal glycemic control is to increase TIR to more than 70%, while simultaneously reducing TBR to less than 4%, while minimizing severe hypoglycemia to less than 1%, as proposed by the Advanced Technologies and Treatments for Diabetes (ATTD) panel. However, several studies have indicated that the TIR goal is quite difficult to achieve in pediatric patients who have remarkable interindividual and day-to-day glycemic variation due to their irregular lifestyles. Previous studies have demonstrated that patients without an automated insulin delivery system are unlikely to attain the recommended glycemic goals. On the other hand, reduction of hypoglycemia, particularly minimizing severe hypoglycemia, is a critical issue in the effective management of children with type 1 diabetes. Frequent episodes of severe hypoglycemia and hypoglycemia can cause lasting neurological damage. Accordingly, we propose reducing the TBR to less than 5%, rather than just targeting the TIR to more than 70%. In CGM metrics this should be the cardinal glycemic goal for pediatric patients who are either being treated with multiple daily injections of insulin or a conventional insulin pump, but who are not using an automated insulin delivery system.

Aims/Introduction We examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes. Materials and Methods The study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively. Results The median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was 12 times/day were categorized as the high‐frequency group (n = 45). Patients in the high‐frequency group were more likely to be treated with insulin pumps compared with those in the low‐frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high‐frequency group showed significantly greater TIR than the low‐frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high‐frequency group showed significantly lower HbA1c levels than the low‐frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P 12 times/day might contribute to better glycemic outcomes in real‐world practice in children with type 1 diabetes., Patients with a higher scanning frequency had better glycemic control, with greater target glucose range and lower glycosylated hemoglobin level, compared with those with lower scanning frequency. Frequent scanning of >12 times per day using flash glucose monitoring might contribute to better glycemic outcomes in children with type 1 diabetes.

We investigated serum C-peptide immunoreactivity (CPR) levels in registered data from a multi-center collaborative nationwide type 1 diabetes study. The CPR levels were obtained from 576 and 409 children during the early registration (2013/2014) and late observation (2016/2017) periods, respectively. The percentages of children with a CPR < 0.1 or < 0.3 ng/mL increased according to the duration since diagnosis. Among patients with 5 or more years since diagnosis, 69% had a CPR < 0.1 and 95% had a CPR < 0.3 in the early registration period. A significant negative correlation was observed between the HbA1c and the CPR levels, and the HbA1c levels were significantly higher among children with a CPR < 0.1 or < 0.3 than among those with a CPR ≥ 0.6 ng/mL. During the late observation period, the prevalence of a CPR < 0.1 ng/mL was 88% among long-standing patients and 77% among patients aged 18–20 yr. Regarding the characteristics of “Responders” with a sustained CPR ≥ 0.6 ng/mL at 5 or more years since diagnosis, six of the seven were adolescent females; five of the seven had an HLA DR4-DQ4 haplotype. When type 1A diabetes mellitus (T1AD) children transit to adult care centers, most of them may have some difficulty in glycemic control because of the depleted endogenous insulin.

This multicenter prospective cohort study followed up Japanese children who had just started GH therapy using a drug delivery device (GROWJECTOR® L) linked to a newly developed smartphone application and analyzed precise medication adherence data stored in GROWJECTOR® L to evaluate the usefulness of the application in improving GH therapy adherence over a 24-wk observation period. Moreover, a questionnaire survey on GH therapy and the smartphone application was conducted, and factors affecting adherence to GH therapy were assessed. This study enrolled 60 children with short stature who had GH deficiency or Turner syndrome or were small for gestational age from 28 Japanese medical institutions and analyzed 57 of them. The median and mean adherence rates after 24 wk of observation were 96% and 93%, respectively. Although adherence rates were significantly lower from wk 16 to wk 20 than from wk 1 to wk 4, cumulative adherence rates remained high throughout the observation period. The questionnaire analysis revealed that most patients actively used the application. Overall, our results suggest that active discussion regarding the development of healthcare systems that contribute toward improving the patient quality of life is warranted.

We previously performed next-generation sequencing-based genetic screening in patients with autoantibody-negative type 1 diabetes, and identified the p.Leu168Pro mutation in HNF1B. Here,we report the clinical course of the patient and the results of functional characterization of this mutation. The proband had bilateral renal hypodysplasia and developed insulin-dependent diabetes during childhood. The pathogenicity of Leu168Pro-HNF1B was evaluated with three-dimensional structure modeling, Western blotting, immunofluorescence analysis and luciferase reporter assays using human embryonic kidney 293 cells. Three-dimensional structure modeling predicted that the Leu168 residue is buried in the DNA-binding Pit-Oct-Unc-specific (POUS) domain and forms a hydrophobic core. Western blotting showed that the protein expression level of Leu168Pro-HNF1B was lower than that of wild-type (WT) HNF1B. Immunofluorescence staining showed that both WT- and Leu168Pro-HNF1B were normally localized in the nucleus. The cells transfected with WT-HNF1B exhibited 5-fold higher luciferase reporter activity than cells transfected with an empty vector. The luciferase activities were comparable between WT-HNF1B/Leu168Pro-HNF1B and WT-HNF1B/empty vector co-transfection. In conclusion, Leu168Pro is a protein-destabilizing HNF1B mutation, and the destabilization is likely due to the structural changes involving the hydrophobic core of POUS. The disease-causing Leu168Pro HNF1B mutation is a loss-of-function mutation without a dominant-negative effect.

We encountered a 12‐year‐old boy with type 2 diabetes who was born small‐for‐gestational age. We described his clinical characteristics and a possible etiological factor for development of hyperglycemia. He developed well with sufficient nutrition and progressed to being overweight at 6 years‐of‐age as a result of a high‐calorie, high‐protein intake diet. He showed a diabetic pattern with a normal insulin response on an oral glucose tolerance test carried out with the urine glucose screening program at schools. He showed a large total fat area of 239.4 cm2; in particular, his visceral fat area was 103.0 cm2 with a high ratio of visceral fat area to subcutaneous fat area (0.76). The present case might show that insulin resistance, possibly as a result of accumulation of a great amount of visceral fat, might be attributed to the pathogenesis of type 2 diabetes in children born small‐for‐gestational age., We described the clinical characteristics and a possible etiological factor for the development of hyperglycemia in a 12‐year‐old boy with type 2 diabetes who was born small‐for‐gestational age.

We investigated the effect of zinc supplementation on growth and serum IGF-1 levels in 10 prepubertal Japanese children with idiopathic short statures, who had serum zinc levels of less than 80 µg/dL. Subjects were started on oral zinc supplementation at a dose of 25 mg once daily. In three children, the doses were increased by 50 mg once daily during the study period of 12 mo. The serum zinc levels rose in all subjects and reached a normal range (beyond 80 µg/dL). However, it was found that zinc supplementation did not promote growth. Although the mean IGF-1 standard deviations significantly increased, the majority did not reach the normal range. There were no significant adverse events other than mild gastrointestinal symptoms in 4 out of 10 subjects during the supplementation period. The most likely reason why growth was not promoted is that the zinc supplementation dosage was not enough to stimulate IGF-1 generation and subsequent growth velocity.

Beckwith-Wiedemann syndrome (BWS) is infrequently associated with adrenocortical carcinoma (ACC) or non-hormone-producing adrenal cytomegaly, but we recently, encountered a single case of adrenal cytomegaly in a patient with BWS, which was difficult to distinguish from androgen-producing adrenocortical carcinoma (ACC). Here, we describe the case of a 4-month-old female who presented with clitoromegaly, hemihypertrophy, and an adrenal mass identified during the prenatal period. The mass was located in detected at the left suprarenal region and detected at 20 weeks of gestational age. At birth, she also presented with clitoromegaly and elevated serum levels of 17α-hydroxyprogesterone, dehydroepiandrosterone, and testosterone at birth and experienced hyper-insulinemic hypoglycemia, which improved following diazoxide therapy. We initially suspected androgen-producing ACC with metastasis and the left adrenal mass was resected accordingly when the patient reached 4 months of age. However, histological examination revealed adrenal cytomegaly. Genetic analysis revealed paternal uniparental disomy, and the patient was finally diagnosed as having BWS. Resection of the left adrenal gland restored the serum androgen levels to normal physiological levels without any recurrence. While it is reasonably well known that BWS is sometimes accompanied by virilization due to androgen-producing ACC, our findings are among the first to suggest that adrenal cytomegaly can also increase androgen hormone production. Thus, we propose that adrenal cytomegaly should be considered one of the differential diagnoses when accompanied with hyperandrogenism in BWS patients.

Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, is a lethal condition and is associated with later-onset cognitive impairment and brain-structural abnormalities, especially in young children. Therefore, reducing the frequency of hypoglycemia and minimizing the occurrence of severe hypoglycemia are critical issues in the management of children and adolescents with type 1 diabetes. Advanced diabetes technologies, including continuous glucose monitoring and sensor-augmented insulin pumps with low-glucose suspension systems, can reduce the frequency of hypoglycemia and the occurrence of severe hypoglycemia without aggravating glycemic control. The hybrid closed-loop system, an automated insulin delivery system, must be the most promising means to achieve appropriate glycemic control with preventing severe hypoglycemia. The use of these advanced diabetes technologies could improve glycemic outcomes and the quality of life in children and adolescents with type 1 diabetes.

Aims/Introduction We compared the results of testing for glutamic acid decarboxylase antibodies (GADAb) using a radioimmunoassay (RIA) and an enzyme‐linked immunosorbent assay (ELISA) in individuals with childhood‐onset type 1 diabetes mellitus. Materials and Methods Serum specimens were collected from 1,024 Japanese children (426 boys and 598 girls) in 2013. The median age at diagnosis was 7 years (0–18 years). The blood specimens were obtained at a median age of 13 years (2–22 years). Results Among the 628 children whose serum specimens were collected within 5 years after diagnosis, the rate of GADAb positivity was 47.9% using RIA and 69.4% using ELISA. The participants were divided into four groups according to their RIA and ELISA results for GADAb as follows: group I (RIA+/ELISA+), group II (RIA+/ELISA−), group III (RIA−/ELISA+) and group IV (RIA−/ELISA−). The clinical and genetic characteristics of group I and group III were quite similar in terms of age at diagnosis, male/female ratio, relatively high positive rates for both autoantibody to protein tyrosine phosphatase IA‐2 and autoantibody to the cation efflux transporter zinc transporter 8, and human leukocyte antigen genotype. Group II contained just five patients, and was characterized by a younger age at diagnosis, low positive rates for both autoantibody to protein tyrosine phosphatase IA‐2 and autoantibody to the cation efflux transporter zinc transporter 8, and a unique human leukocyte antigen genotype. If the positive rates of either autoantibody to protein tyrosine phosphatase IA‐2 or autoantibody to the cation efflux transporter zinc transporter 8 or both were added to the GADAb results using RIA, the percentage of autoimmune type 1 diabetes increased from 47.9% to 78.5%. Conclusions The diagnosis of autoimmune childhood‐onset Japanese type 1 diabetes increased when GADAb results were obtained using a new ELISA method, compared with a previously utilized RIA method., The diagnosis of autoimmune childhood‐onset Japanese type 1 diabetes was increased by the glutamic acid decarboxylase antibodies using a new enzyme‐linked immunosorbent assay in comparison with a previous radioimmunoassay.

BackgroundDiabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). Infants and children with new-onset T1DM may present with DKA, and the risk of cerebral edema is high in infantile DKA.What is new?Neurological deterioration during an episode of DKA is usually attributed to cerebral edema and cerebrovascular accidents. However, cerebral infarction is a very rare complication in infantile DKA.Case presentationWe describe a rare case of infantile cerebral infarction caused by severe DKA in a patient with new-onset T1DM.ConclusionsCerebral infarction is an important intracranial complication in infantile DKA. Careful observation and treatment for DKA during the first 24 h of therapy are necessary in infants with new-onset T1DM because the risk of cerebral infarction is highest during this timeframe.

Purpose The aim was to investigate the characteristics of abdominal fat distribution in Japanese adolescents with type 2 diabetes mellitus. Patients and methods Eighty-six Japanese adolescents with simple obesity or type 2 diabetes mellitus treated between 2002 and 2018 were included. The subjects were classified into the simple obesity group (SO group, n=38) and type 2 diabetes mellitus group (DM group, n=23) by matching average age and gender ratio. The metabolic parameters VFA, SFA, and V/S ratio were compared between the 2 groups. Multivariate logistic regression analysis was performed to identify clinical factors associated with type 2 diabetes mellitus. Linear regression analysis was performed between hemoglobin A1c (HbA1c) and visceral fat area (VFA), subcutaneous fat area (SFA), or VFA-to-SFA ratio (V/S ratio) among all enrolled subjects. Finally, correlation analyses were performed to determine the relationships between VFA, SFA, and V/S ratio and metabolic parameters of the DM group. For the metabolic parameters, serum lipids, alanine aminotransferase (ALT), and HbA1c were measured without fasting. The VFA and SFA at umbilical level were investigated using computed tomography. Results VFA and V/S ratio in DM group were higher than those in SO group (p=0.04 and p

Background and methods We investigated the frequency of zinc deficiency in Japanese children with idiopathic short stature, and evaluated whether serum zinc levels correlated with background factors, including age and standard deviation scores (SDSs) for height and serum insulin-like growth factor (IGF)-1 levels. The study subjects consisted of 89 Japanese children. Results The mean serum zinc level was 79 ± 12 (49–108) μg/dL. Of all the children, 48.3% had a low zinc level, in the 60–80 μg/dL range, and 6.7% had zinc deficiency with a zinc level below 60 μg/dL. The majority with a low zinc level and zinc deficiency were asymptomatic other than for short stature. We found no significant correlations of serum zinc with age, or the SDSs for height and serum IGF-1 levels, in either the entire subject population or those with a zinc level below 80 μg/dL. Conclusions We found a low zinc level to be common in Japanese children with idiopathic short stature, whereas actual zinc deficiency was rare. However, other as yet unknown mechanisms not associated with the growth hormone (GH)-IGF-1 axis could be involved in growth retardation in idiopathic short stature.

Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominant inheritance, onset before 25 years of age, absence of β-cell autoimmunity, and sustained pancreatic β-cell function. To date, mutations have been identified in at least 14 different genes, including six genes encoding proteins that, respectively, correspond to MODY subtypes 1-6: hepatocyte nuclear factor (HNF) 4α (HNF4α), glucokinase (GCK), HNF1α (HNF1 α), pancreatic and duodenal homeobox 1 (PDX1), HNF1β (HNF1 β), and neurogenic differentiation 1 (NEUROD1). Diagnostic tools based on currently available genetic tests can facilitate the correct diagnosis and appropriate treatment of patients with MODY. Candidates for genetic testing include nonobese subjects with hyperglycemia, no evidence of β-cell autoimmunity, sustained β-cell function, and a strong family history of similar-type diabetes among first-degree relatives. Moreover, identification of the MODY subtype is important, given the subtype-related differences in the age of onset, clinical course and progression, type of hyperglycemia, and response to treatment. This review discusses the current perspectives on the diagnosis and treatment of MODY, particularly with regard to the six major subtypes (MODY 1-6).

Aims/Introduction Glucokinase–maturity‐onset diabetes of the young (GCK‐MODY; also known as MODY2) is a benign hyperglycemic condition, which generally does not require medical interventions. The only known exception is increased birthweight and related perinatal complications in unaffected offspring of affected women. As previous data were obtained mostly from white Europeans, the present study analyzed the pregnancy outcomes of Japanese women with GCK‐MODY to better formulate the management plan for this population. Materials and Methods The study participants were 34 GCK‐MODY families whose members were diagnosed at Osaka City General Hospital during 2010–2017. A total of 53 pregnancies (40 from 23 affected women, 13 from 11 unaffected women) were retrospectively analyzed by chart review. Results Birthweights of unaffected offspring born to affected women were significantly greater as compared with those of affected offspring (P = 0.003). The risk of >4,000 g birthweight (16%), however, was lower as compared with that previously reported for white Europeans, and none of the offspring had complications related to large birthweight. Insulin treatment of the affected women resulted in a significant reduction in the birthweights of unaffected offspring. Perinatal complications including small‐for‐gestational age birthweight were found only in affected offspring born to insulin‐treated women. Conclusions In Japanese GCK‐MODY families, unaffected offspring born to affected women were heavier than affected offspring. However, insulin treatment of affected women might not be advisable because of the lower risk of macrosomic birth injury, and an increased risk of perinatal complications in affected offspring.

There are no study reports to clarify the association between gestational age (GA) or anthropometric values at birth, and plasma cortisol levels in the blood of preterm infants at birth and at one month of age. This hospital-based retrospective cohort study included infants born at

We previously performed next-generation sequencing-based genetic screening in patients with autoantibody-negative type 1 diabetes, and identified the p.Leu168Pro mutation in HNF1B. Here,we report the clinical course of the patient and the results of functional characterization of this mutation. The proband had bilateral renal hypodysplasia and developed insulin-dependent diabetes during childhood. The pathogenicity of Leu168Pro-HNF1B was evaluated with three-dimensional structure modeling, Western blotting, immunofluorescence analysis and luciferase reporter assays using human embryonic kidney 293 cells. Three-dimensional structure modeling predicted that the Leu168 residue is buried in the DNA-binding Pit-Oct-Unc-specific (POUS) domain and forms a hydrophobic core. Western blotting showed that the protein expression level of Leu168Pro-HNF1B was lower than that of wild-type (WT) HNF1B. Immunofluorescence staining showed that both WT- and Leu168Pro-HNF1B were normally localized in the nucleus. The cells transfected with WT-HNF1B exhibited 5-fold higher luciferase reporter activity than cells transfected with an empty vector. The luciferase activities were comparable between WT-HNF1B/Leu168Pro-HNF1B and WT-HNF1B/empty vector co-transfection. In conclusion, Leu168Pro is a protein-destabilizing HNF1B mutation, and the destabilization is likely due to the structural changes involving the hydrophobic core of POUS. The disease-causing Leu168Pro HNF1B mutation is a loss-of-function mutation without a dominant-negative effect.

Women with congenital amino acid disorders, including maple syrup urine disease (MSUD), are at risk of metabolic crisis at delivery. There are still only a few case reports of maternal MSUD globally, and we are the first to report the successful perinatal management of a woman with classical MSUD in Japan. A healthy baby was delivered by scheduled cesarean section despite the presence of several uterine fibroids. With precise diet therapy and accurate preparation, she completed the postpartum period without metabolic decompensation. Although her clinical outcome was favorable, she experienced hypoproteinemia at delivery because the available branched-chain amino acid-free medical food did not contain sufficient protein to meet the recommended nutrient intake. Therefore, this case also indicates a potential issue regarding a shortage of variations in specific amino acid-free medical food in Japan, which should be addressed to achieve a better nutrient status of adults with MSUD and other amino acid disorders.

Tall stature is usually defined as a height beyond 97th percentile or more than 2 SD above the mean height for age and sex in a defined population. Familiar tall stature, also known as constitutional tall stature, is the most common cause of tall stature. Overnutrition, obesity, also usually causes overgrowth. Tall stature by itself is not a pathological condition, however, there are a number of disorders associated with tall stature. Some genetic disorders and syndromes may be associated with mental retardation and various complications. Therefore, recognition of tall stature and revealing the underlying pathogenic causes and making the diagnosis are important not to miss the serious conditions and to provide adequate medical care and genetic counseling. Pathological causes for tall statute include endocrine disorders, such as excessive growth hormone secretion, hyperthyroidism, precocious puberty and lipodystrophy, chromosome disorders, such as Trisomy X (47, XXX female), Klinefelter syndrome (47, XXY), XYY syndrome (47, XYY male) and Fragile X syndrome, and syndromes and metabolic disorders, such as Marfan syndrome, Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome, Sotos syndrome and Homocystinuria. Children may require growth reductive treatment if the predicted adult height would be excessive and unacceptable. Some hormonal, high doses of sex steroids, or surgical, bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula, treatment is currently available to reduce adult height.

Background We compared insulin resistance and glucose metabolism during growth hormone (GH) therapy between 43 short children born small-for-gestational age (SGA) and 42 children identifies as growth hormone deficiency (GHD). Methods The study compared fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI) and homeostasis model assessment insulin resistance index (HOMA-IR) during 24-month GH therapy between the two groups. Results Mean FPG, fasting IRI, and HOMA-IR values at 3-month GH therapy were significantly higher than those before and at 12- and 24-month GH therapy in both groups. These markers were significantly higher in short children born SGA than GHD children until 12-month GH therapy but were not different at 24-month GH therapy in both groups. Conclusions The increased secretion of insulin observed in short children born SGA might be a compensatory mechanism for the prevention of hyperglycemia that can progress to diabetes mellitus. However, these metabolic markers gradually declined after 3 months of GH therapy and returned to baseline values at 24 months. These results suggest that short children born SGA have greater insulin resistance than GHD children at the early period of GH therapy, however, increased insulin resistance is improved over a long period. (194 words).

BACKGROUND We aimed to investigate the significance of the C-peptide levels on a glucagon stimulation test (GST) conducted soon after diagnosis as a predictive marker for residual β-cell function over time in Japanese children with type 1 diabetes (TD1). METHODS We retrospectively enrolled 65 Japanese children (25 male, 40 female; age

We assessed the significance of recommendations from the international consensus on continuous glucose monitoring (CGM)-derived metrics in Japanese children and adolescents with type 1 diabetes. Eighty-five patients (age, 13.5 ± 4.7 years) who wore the FreeStyle® Libre for a 28-day period were enrolled in this study. Seventy-three patients were treated with multiple daily injections of insulin and 12 with insulin pump therapy without using a sensor-augmented pump or a predictive low-glucose suspend-function pump. We evaluated the relationship between CGM-derived metrics: time in range (TIR: 70-180 mg/dL), time below range (TBR: 180 mg/dL), and laboratory-measured HbA1c and estimated HbA1c (eA1c) levels calculated from the mean glucose values. The TIR was 50.7 ± 12.2% (23-75%), TBR was 11.8 ± 5.8% (2-27%), and TAR was 37.5 ± 13.5% (9-69%). The TIR was highly correlated with HbA1c level, eA1c level, and TAR, but not with TBR. An HbA1c level of 7.0% corresponded to a TIR of 55.1% (95% CI: 53.7-56.5%), whereas a TIR of 70% corresponded to an HbA1c level of 6.1% (95% CI: 5.9-6.3%). The results of eA1c levels were similar to those observed for HbA1c levels. From these findings, we conclude that low rates of a recommended TIR of 70% may be due to less use of advanced technology and insufficient comprehensive diabetes care. Ethnic characteristics including lifestyle and eating customs may have contributed to the result. CGM-derived targets must be individualized based on ethnic characteristics, insulin treatment and diabetes care, and needs of individuals with diabetes.

BACKGROUND We assessed the association between scanning frequency of flash glucose monitoring (FGM) and continuous glucose monitoring (CGM)-derived glycemic markers in children and adolescents with type 1 diabetes. METHODS Subjects consisted of 85 children and adolescents with type 1 diabetes using FGM. We assessed the association between scanning frequencies of FGM- and CGM-derived metrics: Time in range (TIR) (70-180 mg/dL), time below range (TBR) ( 180 mg/dL), and other glycemic markers - laboratory-measured HbA1c and CGM-estimated glucose and HbA1c (eA1c) levels in the subjects. RESULTS The mean number of scans was 11.5 ± 3.5 (5-20) times per day, and scanning was most frequently conducted during a period of 18-24 h. Scanning frequency showed significant positive correlation with TIR (r = 0.719, P < 0.0001) and inverse correlation with time above range (r = -0.743, P < 0.0001), but did not correlate with TBR. There were also significant inverse correlations between scanning frequency and glucose, HbA1c, and eA1c levels (r = -0.765, -0.815, and -0.793, respectively, P < 0.0001). CONCLUSIONS Frequent glucose testing with FGM decreased hyperglycemia with increased TIR, but did not reduce TBR. Coping with a rapid fall of glucose and unexpected hypoglycemia with more advanced technology might contribute to a reduction in TBR.

Introduction: We evaluated the frequencies of various glycemic markers derived from continuous glucose monitoring in Japanese children and adolescents with type 1 diabetes and assessed the significance of hypoglycemia duration. Methods: We enrolled 85 children and adolescents (36 boys and 49 girls) with type 1 diabetes who used FreeStyle® Libre in the present study. Frequencies of blood glucose levels as time within target range (TIR; 70–180 mg/dL), time below target range (TBR; 180 mg/dL) were assessed during a 3-month study period. Furthermore, we evaluated the intraday frequencies of TBR and TBER. Results: The mean frequencies of TIR, TBR, and TAR were 52.7 ± 11.3%, 10.8 ± 5.4%, and 36.5 ± 10.8%, respectively, whereas the mean frequency of TBER was 1.1 ± 0.9% (0–3.0%); there was no clinical episode of severe hypoglycemia. The mean frequency of TBR was significantly greater in 0–6 h (16.9 ± 5.2%) than in 6–12 h (7.8 ± 2.9%) and 18–24 h (6.8 ± 4.8%; p < 0.01) time zones, respectively. Discussion/Conclusion: We found similar TIR and comparatively higher TBR frequencies, particularly during sleep, than those that were previously reported. Possible reasons for the higher frequency of TBR include differences in the quality of insulin treatment and diabetes care between the present study and the European studies. The utilization of advanced technologies, such as a predictive low-glucose suspend-function pump or closed-loop therapy, can reduce the frequency of TBR, with a consequent increase in TIR frequency and comprehensive improvement in glycemic control.