Search

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.

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

We report our experience with needlescopic splenectomy (NS) for the surgical treatment of idiopathic thrombocytopenic purpura using a 3-mm needlescope with three ports. One patient was male and two were females, and their mean age was 58 years. The patient was placed in the right lateral decubitus position. The first 12-mm port was introduced through the lateral margin of the left rectus abdominis muscle, and the other two 3-mm ports were inserted in the left upper quadrant. NS was performed by a standard technique under the observation of 3.3-mm needlescope. The surgical procedure was successfully completed in all the patients. The mean duration of surgery, intra-operative bleeding volume and post-operative hospital stay were 176 min, 70 ml and 4.7 days, respectively. There were no particular peri-operative complications in spite of dense adhesions or simultaneous laparoscopic procedures. Our method is safe and feasible with low morbidity and without impairing cosmetic benefits.

A 73-year-old man with prior history of duodenal ulcer has been undergoing periodic upper gastrointestinal endoscopy since 1999. In 2017, a 25-mm submucosal tumor-like protrusion was detected in the lesser curvature of the upper stomach; histological examination of the lesion revealed gastric adenocarcinoma of fundic gland type. En bloc resection was achieved using endoscopic submucosal dissection. The patient was histopathologically diagnosed with gastric adenocarcinoma of fundic gland type arising from heterotopic gastric glands. Immunohistochemical staining was positive for MUC5AC, MUC6, pepsinogen I, and proton pump but negative for MUC2 and CD10. Moreover, the patient’s Ki-67 labeling index score was extremely low. The presence of MUC5AC indicated that the tumor differentiated to the foveolar epithelium and fundic glands. Gastric adenocarcinoma of fundic gland type that differentiates to several directions has a higher malignant potential than the disease that differentiates to chief cells. A retrospective review of the patient’s previous endoscopic examination revealed that the submucosal tumor-like protrusion existed since 2000; tumor size increased from 8 mm in 2000 to 25 mm in 2017. The present case is rare in that the carcinoma arose from heterotopic gastric glands. Moreover, the 19-year follow-up revealed that the tumor differentiated to the foveolar epithelium, considered as having high-grade malignancy.

Hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2) for 1 h a day was shown to improve exercise capacity. The present study was designed to reveal whether the daily exposure time affects exercise performance and metabolism in skeletal and cardiac muscles. Male mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Trained mice were then subjected to hybrid training (HT, endurance exercise for 30 min followed by sprint interval exercise for 30 min). Hyperbaric exposure was applied following daily HT for 15 min (15HT), 30 min (30HT), or 60 min (60HT) for 4 weeks. In the endurance capacity test, maximal work values were significantly increased by 30HT and 60HT. In the left ventricle (LV), activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase, citrate synthase, and carnitine palmitoyl transferase (CPT) 2 were significantly increased by 60HT. CPT2 activity levels were markedly increased by hyperbaric exposure in red gastrocnemius (Gr) and plantaris muscle (PL). Pyruvate dehydrogenase complex activity values in PL were enhanced more by 30HT and 60HT than by HT. Protein levels of N‐terminal isoform of PGC1α (NT‐PGC1α) protein were significantly enhanced in three hyperbaric exposed groups in Gr, but not in LV. These results indicate that hyperbaric exposure for 30 min or longer has beneficial effects on endurance, and 60‐min exposure has the potential to further increase performance by facilitating fatty acid metabolism in skeletal and cardiac muscles in highly trained mice. NT‐PGC1α may have important roles for these adaptations in skeletal muscle., Effects of the duration of daily hyperbaric exposure on metabolic enzyme activity levels for fatty acid oxidation

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).

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.

BACKGROUND We conducted an annual urine glucose screening program at schools, and diagnosed schoolchildren with diabetes at an early stage of the disease. We also identified some cases of renal glucosuria (RG), based on positive urine glucose with normal glucose tolerance. METHODS During 2000-2015, 3 309 631 schoolchildren participated in the screening program. The positive rate for glucosuria in the first test was approximately 0.1%, whereas on repeat urine test it was approximately 0.05%. In total 350 schoolchildren were positive for glucosuria on detailed examination. Oral glucose tolerance test (OGTT) was also used to evaluate glucose intolerance. RESULTS One hundred and two schoolchildren (29.7%) were diagnosed with diabetes, whereas RG was identified in 246 (70.3%) with normal glucose metabolism. In regard to the characteristics of RG, the percentage of boys was 50.3%, and the mean age at diagnosis was 11.2 ± 2.4 years. Twenty-eight children (11.4%) were overweight (body mass index standard deviation score [BMI-SDS] > +2.0 SD), whereas five (2.0%) were underweight (BMI-SDS < -2.0 SD). First-degree family history was suspected in 176 cases (71.5%). All RG subjects had normal glucose tolerance in the absence of insulin resistance and decreased insulin secretion (homeostasis model assessment for β-cell function, 78.8 ± 59.5%) on OGTT. CONCLUSIONS RG is not rare in Japanese schoolchildren with glucosuria. This disorder seems to have a strong genetic background, and to involve less growth retardation and weight loss than expected despite continuous excretion of glucose in urine.

New findings What is the central question of this study? Intermittent hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2 ) enhances endurance capacity by facilitating oxidative and glycolytic capacities in skeletal muscle. It remains unclear whether this strategy enhances endurance performance in well-trained individuals. What is the main finding and its importance? Hyperbaric exposure with endurance training enhanced oxidative and glycolytic capacities and protein levels of mitochondrial transcription factor A, dynamin-related protein-1 and heat shock protein 70. Hyperbaric exposure with sprint interval training increased the proportion of type I muscle fibres and promoted capillary growth and muscle fibre hypertrophy. These results may lead to a new strategy for enhancing exercise capacity in well-trained mice. Abstract The study was designed to clarify the mechanisms by which hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2 ) improves endurance and interval exercise capacities in highly trained mice. Male mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Voluntary running markedly increased maximal endurance capacity by 6.4-fold. Trained mice were then subjected to either endurance treadmill training (20-32.5 m min-1 ) or sprint interval training (5 s run-10 s rest, 30-42.5 m min-1 ) with (HypET or HypSIT, respectively) and without (ET or SIT, respectively) 1 h hyperbaric exposure for 4 weeks. Maximal endurance capacity was significantly increased by HypET and HypSIT, and maximal interval capacity was significantly enhanced by HypSIT. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were markedly increased after HypET and HypSIT. Activity levels of 3-hydroxyacyl-CoA-dehydrogenase, citrate synthase and phosphofructokinase in the red gastrocnemius muscle were increased more by HypET than by ET. Protein levels of mitochondrial transcription factor A, dynamin-related protein-1 and heat shock protein 70 were increased more by HypET than by ET. The proportion of type I fibres in the soleus muscle was remarkably increased by HypSIT. Capillary-to-fibre ratio values in the white gastrocnemius were increased more by HypSIT than by SIT. These results suggest that hyperbaric exposure has beneficial effects for endurance and interval training to improve exercise capacity in highly trained mice.

Background The prognosis of non-shockable out-of-hospital cardiac arrest is worse than that of shockable out-of-hospital cardiac arrest. We investigated the associations between the etiology and prognosis of non-shockable out-of-hospital cardiac arrest patients who experienced the return of spontaneous circulation after arriving at hospital. Methods and Results All subjects were extracted from the SOS-KANTO 2012 study population. The subjects were 3,031 adults: (i) who had suffered out-of-hospital cardiac arrest, (ii) for whom there were no pre-hospital data on ventricular fibrillation/pulseless ventricular tachycardia until arrival at hospital, (iii) who experienced the return of spontaneous circulation after arriving at hospital. We compared the patients' prognosis after 1 and 3 months between various etiological and presumed cardiac factors. The proportion of the favorable brain function patients that developed pulmonary embolism or incidental hypothermia was significantly higher than that of the patients with presumed cardiac factors (1 month, P

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

Methylation defects in the imprinting locus at chromosome 6q24 result in transient neonatal diabetes and small-for-gestational age (SGA) births (1). These phenotypes are primarily ascribed to the overexpression of PLAGL1, a paternally expressed gene on 6q24 that regulates cell cycle and apoptosis (2). Paternal uniparental disomy involving 6q24, as well as copy-number gains of paternal PLAGL1 alleles and epimutations in maternal alleles, have been identified as the causes of hypomethylation at the differentially methylated region (DMR) of PLAGL1 (3, 4). Recently, Yorifuji et al. reported the identification of 6q24 uniparental disomy in three patients with childhood-onset non-autoimmune diabetes mellitus (5). The three patients were identified through methylation-specific PCR analysis of the PLAGL1 DMR of 113 patients clinically suspected of having maturity-onset diabetes of the young (MODY). These results expanded the phenotypic consequences of 6q24 methylation defects to include MODY-like manifestations without a history of neonatal diabetes. However, the frequency of 6q24 methylation defects among patients with childhood-onset non-autoimmune diabetes remained unknown.

Background: Marfan syndrome can cause life-threatening aortic complications. We investigated the relationship between FBN1 genotype and severe aortopathy (aortic root replacement, type A dissections, and related death). Methods: We evaluated 248 patients with pathogenic or likely pathogenic FBN1 variants. The variants were classified as haploinsufficient type (HI, n=93) or dominant-negative type (DN, n=155) based on their location and predicted amino acid alterations, and we examined the effects of the FBN1 genotype on severe aortic events (aortic root replacement, type A dissections, and related death). RESULTS: The cumulative event-free probability was significantly lower in the HI group than in the DN group (adjusted hazard ratio, 2.1; 95% confidence interval, 1.4 -3.2; P Conclusions: DN-CD+HI patients should be monitored more carefully than DN-nonCD patients for rapid development of aortic root aneurysms.

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu-like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics.

Background Neurological manifestations caused by hypoglycemia range from reversible focal deficits and transient encephalopathy to irreversible coma or death. Recently, high signal intensity lesions in the splenium of the corpus callosum on diffusion-weighted magnetic resonance imaging were reported in adults experiencing hypoglycemia. However, patients presenting with agraphia are rare. Subject and methods We examined a 17-year-old left-handed female patient with type 1 diabetes who exhibited transient left agraphia with a reversible splenium lesion of the corpus callosum on diffusion-weighted imaging caused by hypoglycemia, which was improved with blood glucose management alone. Conclusion This rare case indicates that agraphia, a sign of callosal disconnection syndrome, can result from a reversible splenial lesion of the corpus callosum caused by hypoglycemia.

Background Mechanical cardiopulmonary resuscitation ( mCPR ) for patients with out‐of‐hospital cardiac arrest attending the emergency department has become more widespread in Japan. The objective of this study is to determine the association between the mCPR in the emergency department and clinical outcomes. Methods and Results In a prospective, multicenter, observational study, adult patients with out‐of‐hospital cardiac arrest with sustained circulatory arrest on hospital arrival were identified. The primary outcome was survival to hospital discharge. The secondary outcomes included a return of spontaneous circulation and successful hospital admission. Multivariate analyses adjusted for potential confounders and within‐institution clustering effects using a generalized estimation equation were used to analyze the association of the mCPR with outcomes. Between January 1, 2012 and March 31, 2013, 6537 patients with out‐of‐hospital cardiac arrest were eligible; this included 5619 patients (86.0%) in the manual CPR group and 918 patients (14.0%) in the mCPR group. Of those patients, 28.1% (1801/6419) showed return of spontaneous circulation in the emergency department, 20.4% (1175/5754) had hospital admission, 2.6% (168/6504) survived to hospital discharge, and 1.2% (75/6419) showed a favorable neurological outcome at 1 month after admission. Multivariate analyses revealed that mCPR was associated with a decreased likelihood of survival to hospital discharge (adjusted odds ratio, 0.40; 95% confidence interval, 0.20–0.78; P =0.005), return of spontaneous circulation (adjusted odds ratio, 0.71; 95% confidence interval, 0.53–0.94; P =0.018), and hospital admission (adjusted odds ratio, 0.57; 95% confidence interval, 0.40–0.80; P =0.001). Conclusions After accounting for potential confounders, the mCPR in the emergency department was associated with decreased likelihoods of good clinical outcomes after adult nontraumatic out‐of‐hospital cardiac arrest. Further studies are needed to clarify circumstances in which mCPR may benefit these patients.

This study was designed to investigate exercise-induced changes in muscle capillarisation, the mRNA expression of angiogenic genes, and microRNA levels in young and middle-aged rats. Rats in the training groups were subjected to treadmill running 5 days a week for 3 weeks. The exercise protocol for the young (12-week old) group was 20-25 m/min, 40-60 min/day with a gradient of 15%, and for the middle-aged (12-month old) group was 18-20 m/min, 40-60 min/day with a gradient of 5%. The enzyme histochemical identification of capillary profiles was performed on cross-sections of gastrocnemius muscle. Total RNA was isolated, reverse transcription was performed, and mRNA and microRNA levels were determined by real-time PCR. The capillary-to-fibre ratio was significantly increased by exercise training in the young group (by 10%), but only slightly in the middle-aged (by 5%) group. Vascular endothecial growth factor (VEGF) mRNA levels were at significantly higher values after acute exercise (1.6-fold) and the 3-week training protocol (1.9-fold) in the young group, but not in the middle-aged group. VEGF protein expression levels were significantly increased after training in the young group only. Endothelial nitric oxide synthase, VEGF-R2 and thrombospondin-1 mRNA levels were significantly lower in the middle-aged group than in the young group. Anti-angiogenic miR-195 levels were significantly enhanced by exercise training in the middle-aged group only. These results indicated that the exercise-induced adaptation of muscle capillarity was attenuated in middle-aged rats, possibly by the lower induction of VEGF and up-regulation of anti-angiogenic miRNA expression.

The first-line pharmacological treatment for patients with maturity-onset diabetes of the young type 1 (MODY1) and maturity-onset diabetes of the young type 3 (MODY3) are sulfonylureas (SUs) or insulin. However, several reports have suggested the possibility of using incretin-associated drugs, including dipeptidyl-peptidase-4 (DPP-4) inhibitors, for the treatment of patients with these types of MODY. Here we report a case of a pediatric patient with MODY1 who was successfully treated with a DPP-4 inhibitor, alogliptin. A 13-yr-old Japanese girl with diabetes was initially treated with insulin for 5 mo. After diagnosis of MODY1, confirmed via a genetic analysis, treatment was changed from insulin to alogliptin. SUs were prescribed temporarily, but monotherapy with alogliptin finally resulted in good glycemic control. After changing to alogliptin, the patient maintained optimal glycemic control with glycated hemoglobin levels of 6.3–7.0% while maintaining substantial β-cell function. No adverse events associated with alogliptin were observed. These results suggest that DPP-4 inhibitors may be a potential treatment for patients with MODY1 at the early stage of the disease when residual insulin secretion is still being sustained.

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

This study implemented a randomized crossover design to evaluate the efficacy and safety of switching from insulin glargine (IGlar) to insulin degludec (IDeg) in 18 children (11 males, 7 females; age 11.0 ± 0.5 years) with type 1 diabetes. All subjects had previously used IGlar once daily at bedtime. We compared fasting plasma glucose (FPG) and HbA1c levels, frequencies of overall and nocturnal (2200 h - 0659 h) hypoglycemia, and basal insulin dose at the baseline with those measured during a 24-week period during which IGlar or IDeg was administered in combination with pre-meal rapid acting insulin analogues. IDeg was initially given at the same dose as IGlar but was subsequently titrated to achieve FPG levels of 90-140 mg/dL. There were no significant changes in FPG and HbA1c levels from the baseline during the 24-week study period with IGlar or IDeg. The daily basal insulin dose did not significantly differ with IGlar or IDeg. Although the frequencies of overall hypoglycemia were similar, nocturnal hypoglycemia significantly decreased at 12 and 24 weeks from the baseline with IDeg use (2 ± 0.4 vs. 0 ± 0.3, 0 ± 0.5 episodes/month, both P

We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1 year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5 ± 31.7 to 162.0 ± 27.3 mg/dL for breakfast, and from 191.1 ± 33.3 to 161.1 ± 24.5 mg/dL for dinner (P

Natural killer (NK)/T-cell lymphomas exhibit aggressive tumor behavior and have a poor prognosis. Recently, self-limited pseudomalignant NK-cell proliferative disorders of the stomach mimicking NK/T-cell lymphomas have been recognized. We report a rare case of lymphomatoid gastropathy in a 71-year-old female. The patient underwent esophagogastroduodenoscopy (EGD) because of slight epigastric discomfort which revealed a 10-mm, reddish, flat elevation with erosion on the posterior wall of the lower gastric body. Histological examination of biopsy specimens showed atypical NK/T cell infiltration with cytoplasmic CD3+, CD4-, CD5-, CD7+, CD8-, CD16-, CD20-, CD56+, CD68-, CD117-, MPO-, TIA1+, and granzyme B+. Epstein-Barr virus-encoded RNA in situ hybridization was negative. Three months later, repeated endoscopic examination surprisingly revealed spontaneous regression of the lesion without any treatment. It is important that endoscopists consider this rare entity in the differential diagnosis, and excessive treatment should be avoided.

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.

In recent years, many experiments have investigated the impact of dietary amino acid supplementation on improvements in muscle strength and endurance capacity. However, it is unclear whether this supplementation causes vascular remodelling in skeletal muscle. This review focused on the effects of L-arginine and/or L-ornithine supplementation on capillary growth in cardiac and skeletal muscles. Although the chronic administration of 4% L-arginine did not improve capillarization in rat cardiac and hind-leg muscles, it facilitated exercise-induced capillary growth via vascular endothelial growth factor (VEGF) protein upregulation. In middle-aged rats, moderate intensity endurance training for 6 weeks did not cause capillary growth, whereas training with L-arginine supplementation led to an improvement in capillarization in the hind-leg muscle and left ventricle by promoting VEGF and endothelial nitric oxide synthase (eNOS) protein expression. The administration of L-arginine and L-ornithine for 6 weeks caused a marked increase in capillarization in rat skeletal muscle via the downregulation of endostatin and upregulation of VEGF-R2 protein expression. Moreover, this supplementation facilitated exercise-induced improvements in capillarization in the hind-leg muscles via the downregulation of endostatin and upregulation of VEGF and eNOS protein levels. The evidence presented in this review indicates that L-arginine and/or L-ornithine administration may facilitate capillary growth and endurance exercise capacity. Furthermore, this supplementation may be a useful therapeutic intervention for ischemic-related diseases.

Background The American Heart Association and European Resuscitation Council guidelines for cardiopulmonary resuscitation present rules for termination of resuscitation (TOR) in cases of out-of-hospital cardiac arrest (OHCA). In Japan, only doctors are legally allowed TOR in OHCA cases. Objective This study aimed to develop a new TOR rule that suits the actual situations of the Japanese emergency medical services system. Methods Five different combinations of the TOR rule criteria were compared regarding specificity and positive predictive value (PPV) for 1-month survival with unfavorable neurologic outcomes. The criteria were unwitnessed by emergency medical service personnel, unwitnessed by bystanders, initial unshockable rhythm in the field, initial asystole in the field, no shock delivered, no prehospital return of spontaneous circulation, unshockable rhythm at hospital arrival, and asystole at hospital arrival. Results A total of 13,291 cases were included. The following combination provided the highest specificity and PPV for predicting 1-month unfavorable neurologic outcomes and death: unwitnessed by bystanders, initial asystole in the field, and asystole at hospital arrival. The specificity and PPV for the combination of the three criteria for predicting 1-month unfavorable neurologic outcomes were 0.992 and 0.999, and for predicting death at 1 month after OHCA were 0.986 and 0.998, respectively. Conclusions OHCA patients fulfilling the criteria unwitnessed by bystanders and asystole in the field and at hospital arrival had universally poor outcomes. Termination of resuscitation after hospital arrival for these patients may decrease unwarranted treatments.

This study was designed to (1) investigate the effects of acute short‐duration intermittent hypoxia on muscle mRNA and microRNA expression levels; and (2) clarify the mechanisms by which short‐duration intermittent hypoxia improves endurance capacity. Experiment‐1: Male mice were subjected to either acute 1‐h hypoxia (12% O 2 ), acute short‐duration intermittent hypoxia (12% O 2 for 15 min, room air for 10 min, 4 times, Int‐Hypo), or acute endurance exercise (Ex). The expression of vascular endothelial growth factor‐A mRNA was significantly greater than the control at 0 h post Ex and 6 h post Int‐Hypo in the deep red region of the gastrocnemius muscle. miR‐16 expression levels were significantly lower at 6 and 10 h post Int‐Hypo. Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1 α ) mRNA levels were significantly greater than the control at 3 h post Ex and 6 h post Int‐Hypo. miR‐23a expression levels were lower than the control at 6–24 h post Int‐Hypo. Experiment‐2: Mice were subjected to normoxic exercise training with or without intermittent hypoxia for 3 weeks. Increases in maximal exercise capacity were significantly greater by training with short‐duration intermittent hypoxia (IntTr) than without hypoxia. Both 3‐Hydroxyacyl‐CoA‐dehydrogenase and total carnitine palmitoyl transferase activities were significantly enhanced in IntTr. Peroxisome proliferator‐activated receptor delta and PGC‐1 α mRNA levels were both significantly greater in IntTr than in the sedentary controls. These results suggest that exercise training under normoxic conditions with exposure to short‐duration intermittent hypoxia represents a beneficial strategy for increasing endurance performance by enhancing fatty acid metabolism in skeletal muscle.

Aim To compare the injection frequencies employed and the basal-to-total insulin dose ratios obtained when glargine (G) and detemir (D) are used in children with type 1 diabetes mellitus (T1DM) treated by basal–bolus therapy (BBT).

We examined the correlation between plasma glucose (PG) and hemoglobin A1c (HbA1c) to evaluate the usefulness and limitations of applying the new diagnostic criteria for diabetes to Japanese pediatric patients. Data were collected from 298 school children who took an oral glucose tolerance test (OGTT) at a school-based urinary glucose screening program in the Tokyo Metropolitan Area between 1988 and 2009. Mean (SD) age of the children was 11.9 (2.5) years. Male-to-female ratio was 1:1.1. Children were diagnosed with renal glucosuria (n=146), diabetes mellitus (n=133), or the Japan Diabetes Society (JDS) "borderline type" (n=19). Median (range) values of fasting plasma glucose (FPG), 2-h plasma glucose in an OGTT (OGTT-2h), and HbA1c were 101 (76-378) mg/dL, 146.5 (57-563) mg/dL, and 6.05 (4.7-14.1) %. The correlation between PG and HbA1c was analyzed using least squares regression, and HbA1c was found to highly correlate with PG. From estimated regression equations, mean values of FPG and OGTT-2h corresponding to an HbA1c of 6.5% were calculated to be 111.4 mg/dL and 170.4 mg/dL. The mean values of HbA1c corresponding to an FPG of 126 mg/dL and OGTT-2h of 200 mg/dL were calculated to be 7.5% and 7.8%. The mean values of PG corresponding to HbA1c of 6.5% were lower than found in adults as analyzed by JDS. The mean values of HbA1c corresponding to diabetic type PG were higher than found in adults.

High-echoic objects in the hepatic vessels of patients with cardiopulmonary arrest (CPA) are frequently detected by ultrasonography.To demonstrate this phenomenon and clarify its clinical characteristics.In a tertiary care academic medical centre, 203 CPA patients were evaluated by ultrasonography. CT determined the origin and location of high-echoic objects detected in the liver. The frequency and characteristics of this phenomenon were investigated. The background, laboratory data and survival rate were compared between patients with and without high-echoic objects.High-echoic objects were seen in 73 (36.0%) patients and could clearly be detected in the hepatic veins of 41 (56.2%) patients. CT confirmed that these were gas in 27 of 53 patients, and were clearly visible in the hepatic veins in 12 (44.4%) patients. Hepatic portal venous gas was not identified. Compared to patients without high-echoic objects, witnessed arrest (p0.001), bystander cardiopulmonary resuscitation (p=0.005), ventricular fibrillation or pulseless electrical activity (p=0.012) and return of spontaneous circulation (p=0.018) were significantly less frequent in patients with high-echoic objects. These patients had a lower incidence of survival to discharge (1.4% vs 7.7%, p=0.100). Multivariate analysis showed that absence of high-echoic objects was a marginally significant factor in association with return of spontaneous circulation (p=0.052).High-echoic objects were often observed on ultrasonography in CPA patients; these objects were considered hepatic venous gas. The presence of high-echoic objects may be a poor prognostic sign in patients with CPA.

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. Methods: The study was conducted in 60 Japanese children, aged 13.3 ± 4.6 years, with type 1 diabetes for at least 3 years of diabetes. Most of the subjects had absent pancreatic β-cell function. We compared the glucagon levels among patient groups stratified according to the 2-hour postprandial levels (

We incidentally encountered an anomaly of the cervical vertebrae during orthodontic examination of an 8-year-old boy with cleft lip and palate. Klippel-Feil syndrome was diagnosed by the orthopedic specialist to whom he had been referred for detailed examination. This case report shows the results of axial multislice-helical computed tomography with three-dimensional reconstructions of the cervical vertebrae. Furthermore, we evaluated the frequency of congenital anomalies on lateral cephalogram in patients with cleft lip and palate or cleft palate and non-cleft controls from among all patients in our orthodontic clinic.

目的．肺癌術後患者にみられた肺抗酸菌症例についての検討を行った．方法．1996～2007年に当院で経験した，肺癌術後の肺結核症（pulmonary tuberculosis：PTB）および肺非結核性抗酸菌症（pulmonary non-tuberculous mycobacteriosis：PNTM）の24例を対象に，病歴や経過，検査所見，X線所見などを後ろ向きに解析した．結果．肺抗酸菌症の内訳はPTB 14例，PNTM 10例（肺M. avium complex症9例，肺M. kansasii症1例）で，男性（17例），高齢者（15例），術後5年以内（15例），術側肺（18例）に多くみられた．PTB例では肺癌再発（7例），結核治療歴（6例），他臓器癌の既往，performance status（PS）2以上（各5例）などを認め，全身状態の悪化に基づく内因性再燃が示唆された．PNTMでは全身的要因をほとんど認めなかったが，術側肺の発症が9例を占め，手術に伴う肺局所環境の悪化に伴う感染，増悪が示唆された．治療について，PTBでは診断の遅れがなければ治療経過，予後は良好であったが，PNTMでは治療にも関わらず，病変が進展し，肺アスペルギルス症などを併発し，死亡する症例もみられた．結論．肺癌術後患者の管理においては全身状態やX線所見に注意を払い，肺抗酸菌症を的確に診断することが重要である．

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

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

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). Design: The study involved 112 Japanese schoolchildren, 45 males and 67 females aged 12.9 ± 1.5 yr, who were diagnosed as having T2DM. The body weight, blood pressure and fasting serum triglyceride (TG), and high-density lipoprotein cholesterol cholesterol (HDL-C) levels were also measured at diagnosis. The criteria adopted for the diagnosis of MS were as follows; i.e., TG ≥150 mg/dL, HDL-C

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.

We examined pathogenic characteristics in Japanese children with type 1 diabetes presenting before 5 years of age. The subjects were 23 Japanese children, 9 males and 14 females, 1.1-4.8 yr of age at diagnosis. The majority had severe metabolic decompensation accompanied by complete absence of β-cell function at diagnosis. We found a high frequency of preceding viral illness (41.7%) among them. The prevalence of antibodies to GAD and IA-2 at diagnosis in young children were significantly lower than those in older cases diagnosed after 5 yr of age (31.6% vs. 86.3%, 47.1% vs. 82.5%, respectively). These findings suggest that non-autoimmune mechanisms or age-related differences in autoimmunity could be involved in the pathogenesis of diabetes in young children. In regard to diabetes-related HLA-DRB1 and DQB1 alleles, all subjects had high-risk genotypes in both alleles. On the other hand, none of the patients had any of the protective genotypes in either allele. In regard to haplotypes, the frequencies of DRB1*0405-DQB1*0401 and DRB1*0901/ DQB1*0303 were 60.9% and 52.2%, respectively, and both these haplotypes are associated with strong susceptibility to type 1 diabetes. Patients with early-childhood onset may have diabetes-related autoimmunity and genetic backgrounds different from those of patients diagnosed at a later age.

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