Correction: Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

[This corrects the article DOI: 10.1007/s13340-023-00646-w.].

Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

The significance of diagnosing gestational diabetes mellitus (GDM) in early pregnancy is controversial. We used the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria to investigate whether clinical background and neonatal outcomes differ depending on when GDM is diagnosed in early or late pregnancy. This was a single-center, observational study conducted between November 2012 and March 2020 at St. Marianna University Hospital (Kawasaki, Japan). We compared the background and perinatal outcomes of patients with GDM depending on the time of diagnosis (at < 24 gestational weeks or ≥ 24 weeks). Insulin sensitivity index, homeostasis model assessment of insulin resistance, and ß-cell function were calculated from a 75-g oral glucose tolerance test. Stratified analysis was performed by pre-pregnancy BMI in patients with early GDM. As a result, in the 507 patients, 89.9% gave birth at our hospital. The pre-pregnancy BMI was significantly higher in patients with early GDM than in those with late GDM (the median [interquartile range], 22.7 [20.3, 26.3] and 21.5 [19.3, 23.8] kg/m2, respectively; p = 0.001). Perinatal outcomes were not different between the two groups. However, in the subgroup analysis of patients with early GDM, the prevalence of large-for-gestational-age infants was significantly higher in the group with overweight (15.4% vs 2.1%, respectively; p = 0.008). In conclusion, patients with GDM using the IADPSG criteria in early pregnancy may be treated, especially in patients with pre-pregnancy overweight.

Effects of cooked rice containing high resistant starch on postprandial plasma glucose, insulin, and incretin in patients with type 2 diabetes.

BACKGROUND AND OBJECTIVES: Few studies exist on resistant starch in rice grains. The Okinawa Institute of Science and Technology Graduate University (OIST) has developed a new rice (OIST rice, OR) rich in resistant starch. This study aimed to clarify the effect of OR on postprandial glucose concentrations. METHODS AND STUDY DESIGN: This single-center, open, randomized, crossover comparative study included 17 patients with type 2 diabetes. All participants completed two meal tolerance tests using OR and white rice (WR). RESULTS: The median age of the participants was 70.0 [59.0-73.0] years, and the mean body mass index was 25.9±3.1 kg/m2. The difference in total area under the curve (AUC) of plasma glucose was -8223 (95% confidence interval [CI]: -10100 to -6346, p<0.001) mg·min/dL. The postprandial plasma glucose was significantly lower with OR than with WR. The difference in the AUC of insulin was -1139 (95% CI: -1839 to -438, p=0.004) µU·min/mL. The difference in the AUC of total gastric inhibitory peptide (GIP) and total glucagon-like peptide-1 (GLP-1) was -4886 (95% CI: -8456 to -1317, p=0.011) and -171 (95% CI: -1034 to 691, p=0.673) pmol·min/L, respectively. CONCLUSIONS: OR can be ingested as rice grains and significantly reduced postprandial plasma glucose compared to WR independent of insulin secretion in patients with type 2 diabetes. OR could have escaped absorption not only from the upper small intestine but also from the lower small intestine.

Effects of Elobixibat in Patients with Diabetes and Concomitant Chronic Constipation: an 8-week, Prospective, Single-center, Single-arm Study.

AIMS: To evaluate the efficacy and safety of elobixibat in patients with diabetes and concomitant chronic constipation. METHODS: This was a single-center, single-arm study. Thirty-three patients with diabetes and chronic constipation, as defined by the Rome IV criteria, were treated with elobixibat (10 mg/day) for 8 weeks. Patients recorded stool properties, including spontaneous bowel movements (SBMs) and stool consistency, according to the Bristol Stool Form Scale (BSFS). Quality of life for constipation was evaluated with the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL). RESULTS: Of the 33 eligible patients, 30 completed the study. Elobixibat significantly increased the median (interquartile range) frequency of SBMs per week, from 5.0 (3.0-7.0) at baseline to 6.0 (4.0-7.0] at week 8 (p = 0.030). After 8 weeks, the BSFS score approached 4; the score for normal stool consistency and the JPAC-QOL score significantly improved from 1.05 ± 0.40 at baseline to 0.94 ± 0.53 (p = 0.048); and glycated albumin and serum lipid profiles significantly improved. Stratified analysis revealed that SBMs increased especially in patients with low SBM frequency, in particular in women, older adults, patients without overweight, patients with a long duration of constipation, and patients with diabetic neuropathy. No serious adverse events occurred. CONCLUSIONS: Among patients with diabetes who met the Rome IV criteria for constipation, elobixibat was effective, especially in those with few SBMs at baseline. Improvements in lipid profiles could be an advantage of elobixibat compared with other laxatives. CLINICAL TRIAL REGISTRY: Japan Registry of Clinical Trials registration number: jRCTs031190092.

Correlation between blood ketones and exhaled acetone measured with a semiconducting gas sensor.

Breath acetone (BrAce) has been reported to be useful for monitoring the pathophysiology of patients with diabetes. However, devices that measure BrAce are expensive, complex and uncommon. The FM-001, originally designed to monitor a marker of weight loss in healthy people, is a device for measuring BrAce. The FM-001 is a loading semiconducting gas sensor that is a simple and reusable device. The aim of this study was to evaluate the correlation between blood total ketone bodies (TKB) and BrAce measured with the FM-001 in patients with diabetes. Furthermore, through evaluation of that correlation, we sought to detect patients at high risk of developing diabetic ketoacidosis (DKA). Thirty-five participants (age 52 [40-57], T2DM 32, T1DM 3) were enrolled. Scatter plots and linear regression lines relating BrAce to TKB and the correlation coefficients were calculated. Receiver-operating characteristic analysis was performed to determine the cut-off for predicting patients prone to DKA. The results showed that BrAce strongly correlates with TKB (R= 0.828), and the correlation was stronger in patients whose serum C-peptide was not low. The optimal BrAce cut-off for predicting risk of developing DKA was 3400 ppb (AUC 0.924, sensitivity 73.3%, specificity 100%), which corresponds to a TKB ⩾ 1000µmol l-1. BrAce also weakly correlated with free fatty acid. Thus, BrAce levels measured with the FM-001 strongly correlate with TKB, even in patients with diabetes. This suggests the FM-001 is a simple and potentially useful method for detecting diabetic ketosis. (UMIN-ID: UMIN000038086).

Primary aldosteronism with mild autonomous cortisol secretion increases renal complication risk.

Objective: In primary aldosteronism (PA), renal impairment has been identified as an important comorbidity. Excess cortisol production also may lead to renal damage; thus, concomitant mild autonomous cortisol secretion (MACS) may predispose PA patients to renal disorders. However, there is limited evidence to support this claim. Therefore, this study aimed to determine whether the concurrence of MACS and PA increases the risk of renal complications. Design: This study is a retrospective cross-sectional study. Methods: A total of 1310 patients with PA were stratified into two groups according to 1 mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS (n = 340) and non-MACS (n = 970). The prevalence of renal complications was compared between the group. We also performed multiple logistic regression analysis to determine factors that increase the risk for renal complications. Results: The prevalence of lowered estimated glomerular filtration rate (eGFR) and proteinuria was nearly twice higher in the MACS group than in the non-MACS group. Not only plasma aldosterone concentration (PAC) but also the presence of MACS was selected as independent factors that were associated with the two renal outcomes. The risk of lower eGFR or proteinuria in patients who had MACS and higher levels PAC was several folds higher than in those who had an absence of MACS and lower levels of PAC. Conclusions: MACS is an independent risk factor for renal complications in patients with PA, and MACS concomitant with higher aldosterone secretion in PA patients causes an increase in the risk of developing renal complications.

A retrospective cohort study for the treatment of Asian diabetic ketoacidosis: optimizing initial doses of insulin.

AIM: An insulin dose of 0.1 U/kg/h recommended by Western guidelines occasionally induces a precipitous decreasing blood glucose in Asian diabetic ketoacidosis (DKA). It is known that clinical factors, such as insulin sensitivity, differ between Asians and Americans/Europeans. We investigated how treatment options affect the time to DKA resolution to determine the optimal treatment for Asian DKA patients. METHODS: This was a retrospective cohort study from a single institution in Japan. A total of 34 adult DKA patients were observed. Baseline characteristics and treatment-related parameters were compared between patients whose DKA was resolved within 18 h and those in which it was not. RESULTS: Significant differences were observed in the initial insulin dose (mean [standard deviation]: 0.053 [0.021] versus 0.031 [0.014] U/kg/h; P = 0.003) and the baseline ß-hydroxybutyrate (7.2 [3.2] versus 9.9 [2.6] mmol/L; P = 0.024) and HCO 3 - levels (11.2 [4.1] versus 7.7 [3.1] mmol/L; P = 0.014). Multivariable logistic regression analysis revealed that the initial insulin dose was significantly associated with early resolution of DKA and was independent of basal conditions. Receiver operating characteristic curve analysis indicated that the optimal cut-off point for the initial insulin dose was 0.051 U/kg/h. With an initial insulin dose of 0.051 U/kg/h or higher, early resolution of DKA was obtained in 92.9% of patients. CONCLUSION: An initial insulin dose of more than 0.05 U/kg/h provides an early resolution of DKA in Asian patients. Lower insulin doses significantly delay resolution. These results provide practical information for acute phase treatment of Asian DKA.

Two bacterial glycosphingolipid synthases responsible for the synthesis of glucuronosylceramide and α-galactosylceramide.

Bacterial glycosphingolipids such as glucuronosylceramide and galactosylceramide have been identified as ligands for invariant natural killer T cells and play important roles in host defense. However, the glycosphingolipid synthases required for production of these ceramides have not been well-characterized. Here, we report the identification and characterization of glucuronosylceramide synthase (ceramide UDP-glucuronosyltransferase [Cer-GlcAT]) in Zymomonas mobilis, a Gram-negative bacterium whose cellular membranes contain glucuronosylceramide. On comparing the gene sequences that encode the diacylglycerol GlcAT in bacteria and plants, we found a homologous gene that is widely distributed in the order Sphingomonadales in the Z. mobilis genome. We first cloned the gene and expressed it in Escherichia coli, followed by protein purification using nickel-Sepharose affinity and gel filtration chromatography. Using the highly enriched enzyme, we observed that it has high glycosyltransferase activity with UDP-glucuronic acid and ceramide as sugar donor and acceptor substrate, respectively. Cer-GlcAT deletion resulted in a loss of glucuronosylceramide and increased the levels of ceramide phosphoglycerol, which was expressed in WT cells only at very low levels. Furthermore, we found sequences homologous to Cer-GlcAT in Sphingobium yanoikuyae and Bacteroides fragilis, which have been reported to produce glucuronosylceramide and α-galactosylceramide, respectively. We expressed the two homologs of the cer-glcat gene in E. coli and found that each gene encodes Cer-GlcAT and Cer-galactosyltransferase, respectively. These results contribute to the understanding of the roles of bacterial glycosphingolipids in host-bacteria interactions and the function of bacterial glycosphingolipids in bacterial physiology.

LUBAC accelerates B-cell lymphomagenesis by conferring resistance to genotoxic stress on B cells.

The linear ubiquitin chain assembly complex (LUBAC) is a key regulator of NF-κB signaling. Activating single-nucleotide polymorphisms of HOIP, the catalytic subunit of LUBAC, are enriched in patients with activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), and expression of HOIP, which parallels LUBAC activity, is elevated in ABC-DLBCL samples. Thus, to clarify the precise roles of LUBAC in lymphomagenesis, we generated a mouse model with augmented expression of HOIP in B cells. Interestingly, augmented HOIP expression facilitated DLBCL-like B-cell lymphomagenesis driven by MYD88-activating mutation. The developed lymphoma cells partly shared somatic gene mutations with human DLBCLs, with increased frequency of a typical AID mutation pattern. In vitro analysis revealed that HOIP overexpression protected B cells from DNA damage-induced cell death through NF-κB activation, and analysis of the human DLBCL database showed that expression of HOIP positively correlated with gene signatures representing regulation of apoptosis signaling, as well as NF-κB signaling. These results indicate that HOIP facilitates lymphomagenesis by preventing cell death and augmenting NF-κB signaling, leading to accumulation of AID-mediated mutations. Furthermore, a natural compound that specifically inhibits LUBAC was shown to suppress the tumor growth in a mouse transplantation model. Collectively, our data indicate that LUBAC is crucially involved in B-cell lymphomagenesis through protection against DNA damage-induced cell death and is a suitable therapeutic target for B-cell lymphomas.

Effects of anagliptin on plasma glucagon levels and gastric emptying in patients with type 2 diabetes: An exploratory randomized controlled trial versus metformin.

AIMS: Glucagon has an important role in glucose homeostasis. Recently, a new plasma glucagon assay based on liquid chromatography-high resolution mass spectrometry was developed. We evaluated the influence of a dipeptidyl peptidase-4 inhibitor (anagliptin) on plasma glucagon levels in Japanese patients with type 2 diabetes by using this new assay. METHODS: Twenty-four patients with type 2 diabetes were enrolled in a prospective, single-center, randomized, open-label study and were randomly allocated to 4 weeks of treatment with metformin (1000 mg/day) or anagliptin (200 mg/day). A liquid test meal labeled with sodium [13C] acetate was ingested before and after the treatment period. Samples of blood and expired air were collected over 3 h. Plasma levels of glucose, glucagon, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured, and gastric emptying was also evaluated. RESULTS: Twenty-two patients completed the study (metformin group: n = 10; anagliptin group: n = 12). Glycemic control showed similar improvement in both groups. In the anagliptin group, there was a slight decrease of the incremental area under the plasma concentration versus time curve for glucagon after the test meal (P = 0.048). In addition, the plasma level of active GLP-1 and GIP was increased, and plasma C-peptide was also increased versus baseline. Neither anagliptin nor metformin delayed gastric emptying. CONCLUSIONS: In patients with type 2 diabetes maintained endogenous insulin secretion, anagliptin increased the plasma level of active GLP-1 and GIP in association with a slight stimulation of insulin secretion and slight inhibition of glucagon secretion, but did not delay gastric emptying. Clinical Trial Registry: University hospital Medical Information Network UMIN000028293.

Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death.

T cell-mediated autoimmunity encompasses diverse immunopathological outcomes; however, the mechanisms underlying this diversity are largely unknown. Dysfunction of the tripartite linear ubiquitin chain assembly complex (LUBAC) is associated with distinct autonomous immune-related diseases. Cpdm mice lacking Sharpin, an accessory subunit of LUBAC, have innate immune cell-predominant dermatitis triggered by death of LUBAC-compromised keratinocytes. Here we show that specific gene ablation of Sharpin in mouse Treg causes phenotypes mimicking cpdm-like inflammation. Mechanistic analyses find that multiple types of programmed cell death triggered by TNF from tissue-oriented T cells initiate proinflammatory responses to implicate innate immune-mediated pathogenesis in this T cell-mediated inflammation. Moreover, additional disruption of the Hoip locus encoding the catalytic subunit of LUBAC converts cpdm-like dermatitis to T cell-predominant autoimmune lesions; however, innate immune-mediated pathogenesis still remains. These findings show that T cell-mediated killing and sequential autoinflammation are common and crucial for pathogenic diversity during T cell-mediated autoimmune responses.

Additive effect of Lactobacillus acidophilus L-92 on children with atopic dermatitis concomitant with food allergy.

BACKGROUND: Atopic dermatitis (AD) in infants is often related to food allergies (FA). The beneficial effects of lactic acid bacteria towards allergic diseases have been reported, but there are few reports on their effect and preferable dosages on AD in young children with concomitant FA. OBJECTIVE: To examine additional effects of two different dose of paraprobiotic Lactobacillus acidophilus L-92 (L-92) on the clinical treatment in young children afflicted by AD with diagnosed or suspected FA. METHODS: Fifty-nine AD young children from 10 months to 3 years old, with FA or who had not started to ingest specific food(s) because of high specific IgE levels, were recruited and randomly allocated into L-92 group (daily intake of 20 mg L-92/day) and placebo group. Participants were given test sample with conventional treatment for AD over a 24-week period. The severity of eczema was evaluated using SCORing Atopic Dermatitis (SCORAD) index before intervention, and at 4, 12, and 24 weeks after intervention. RESULTS: After 24 weeks of intervention, a significant decrease in SCORAD was observed only in the L-92 group when compared with the baseline values. Significant decreases in thymus and activation-regulated chemokine (TARC) and total IgE were also detected 24 weeks after intake in the L-92 group compared with the placebo group. CONCLUSION: It was suggested that intake of sufficient amounts of L-92 works as an adjunctive treatment of young children afflicted by AD with diagnosed or suspected FA.

Differing Effect of the Sodium-Glucose Cotransporter 2 Inhibitor Ipragliflozin on the Decrease of Fat Mass vs. Lean Mass in Patients With or Without Metformin Therapy.

BACKGROUND: We previously reported changes of body composition determined by dual-energy X-ray absorptiometry after treatment with ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. In that study, mean body weight was decreased by 3.5 kg (4.3% of the baseline value) after ipragliflozin treatment at 50 mg/day, with fat mass and lean mass showing similar reductions of 1.7 and 1.8 kg, respectively. A long-term decrease of lean mass in patients treated with SGLT2 inhibitors may be associated with loss of skeletal muscle, which could potentially have an impact on quality of life. METHODS: In this post hoc analysis, we investigated whether changes of body composition were influenced by other medications for diabetes in 20 patients (11 men and nine women) who received ipragliflozin for 24 weeks. RESULTS: When we divided the patients into two subgroups with or without metformin treatment, fat mass showed a significant decrease in the ipragliflozin + metformin subgroup and a significantly greater decrease compared to the ipragliflozin subgroup (2.0 kg; 95% confidence interval (CI): 0.1 - 3.9; P = 0.038). Lean mass was significantly decreased in the ipragliflozin subgroup, but the decrease showed no significant difference from that in the ipragliflozin + metformin subgroup (1.9 kg; 95% CI: -4.1 - 0.3; P = 0.087). No significant differences of body composition changes were observed with other antidiabetic agents. CONCLUSIONS: More desirable weight reduction due to preferential fat loss and less muscle loss may be achieved by combining an SGLT2 inhibitor with metformin.

Liraglutide Reduces Visceral and Intrahepatic Fat Without Significant Loss of Muscle Mass in Obese Patients With Type 2 Diabetes: A Prospective Case Series.

BACKGROUND: Glucagon-like peptide-1 receptor agonists have been reported to reduce body fat as well as improving glycemic control in obese patients with type 2 diabetes. However, the maximum dose of liraglutide is limited to 0.9 mg in Japan, while the international dose is 1.8 mg; and the effect of this low dose on body composition has not been assessed in detail. Accordingly, this study was performed to evaluate the effect of liraglutide on body composition when administered at 0.9 mg once daily for 24 weeks. METHODS: Nine patients were enrolled and started liraglutide at 0.3 mg once daily, which was titrated to 0.9 mg once daily after 1 - 2 weeks and continued for 24 weeks. To comprehensively investigate changes of body composition, the body fat and muscle weight were determined by dual energy absorptiometry, visceral fat volume (VFV) and abdominal subcutaneous fat volume (SFV) were measured by abdominal computed tomography (CT), and the intrahepatic lipid content (IHL) was assessed by proton magnetic resonance spectroscopy. Measurements were obtained before starting liraglutide therapy and after 12 and 24 weeks of treatment. RESULTS: Fasting plasma glucose was significantly reduced from 127 ± 22 to 101 ± 14 mg/dL at 24 weeks and hemoglobin A1c (HbA1c) showed significant reduction from 6.4±0.9% to 5.2±0.5%. Body weight was reduced from 103.4 ± 14.7 to 97.0 ± 12.4 kg (mean reduction: 11.7%) and BMI decreased from 37.4 ± 6.4 to 35.0 ± 5.3 kg/m2 (mean reduction: 5.8%). Furthermore, VFV and IHL decreased from 5,192 ± 1,730 to 4,513 ± 1,299 cm3 (mean reduction: 11.9%) and 32.1±12.6% to 15.2±9.2% (mean reduction: 49.2%), respectively, but SFV did not change. Moreover, the fat index was reduced from 14.8 ± 4.4 to 12.9 ± 3.4 kg/m2 (mean reduction: 10.9%), but the skeletal muscle index did not change. CONCLUSIONS: In obese Japanese drug-naive patients who had type 2 diabetes, treatment with liraglutide (0.9 mg once daily for 24 weeks) reduced body fat, especially visceral fat and intrahepatic fat, while having no significant effect on skeletal muscle.

Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.

BACKGROUND: Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape of MECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES). METHODS: We performed WES on 77 MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria. RESULTS: Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including MECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H+ transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2). CONCLUSIONS: Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.

Association of the muscle/fat mass ratio with insulin resistance in gestational diabetes mellitus.

This study assessed the association of muscle mass with insulin resistance, evaluated from the insulin sensitivity index (ISI), in Japanese patients with gestational diabetes mellitus (GDM). Consecutive patients with GDM (n = 96) admitted to St. Marianna University Hospital between October 2015 and March 2018 for initial education and glycemic control were enrolled in a prospective observational study. Insulin resistance was evaluated by measuring the ISI and body composition was assessed by bioelectrical impedance analysis. The subjects were aged 34.4 ± 4.8 years (mean ± SD) and their body mass index (BMI) before pregnancy was 22.3 ± 4.0 kg/m2. Fifty-three patients (55.2%) had a history of diabetes in first-degree relatives. The ISI was 7.2 ± 3.3, appendicular skeletal muscle mass (ASM) was 17.0 ± 2.1 kg, and fat mass (FM) was 18.8 ± 8.2 kg. The ASM/FM ratio was 1.02 ± 0.34. There was a positive correlation between FM and ASM (r = 0.734, p < 0.001). To adjust for confounders when evaluating the association of ASM with ISI, multivariate analysis was conducted using age, family history of diabetes, and BMI as variables. In this analysis, the ASM/FM ratio showed a significant positive correlation with ISI (ß = 0.303, p = 0.020). These findings suggest that inadequate ASM/FM ratio is important for the development of insulin resistance in Japanese patients with GDM. Excessive emphasis on dieting rather than health might increase the risk of GDM by reducing the muscle mass below the level that maintains normal glucose metabolism.

Identifying the factors and root causes associated with the unintentional usage of an adrenaline auto-injector in Japanese children and their caregivers.

BACKGROUND: The unintentional usage of adrenaline auto-injectors may cause injury to caregivers or patients. To prevent such incidents, we assessed the causative factors of these incidents. METHODS: The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which adrenaline auto-injectors were unintentionally used. One hundred cases were reported from June 2015 to March 2016. We identified the root causes of 70 child and 25 adult cases, separately. RESULTS: The incidents occurred with repeated prescriptions as well as the first prescription. Three cases resulted in a failure to administer an adrenaline auto-injector to children with anaphylaxis. Four caregivers used it with improper application (epilepsy or enteritis). Among the child cases, the median age at the time of the incident was 5.5 years (range, 2-14 years). Five children injected the adrenaline auto-injector on their own body trunk. Twenty children were not the allergic patients themselves. Improper management protocol of the device and the child's development were concomitantly involved in most of the cases. A variety of human behaviors were identified as the root causes in the adult cases. At least 34 cases were associated with mix-ups between the actual and training device. CONCLUSIONS: Health workers should provide sufficient education regarding safety use of adrenaline auto-injector for caregivers tailored to their experience levels at both first and repeated prescriptions. Such education must cover anticipatory behavior based on normal child development. Devices should also be further improved to prevent such incidents.

[THE CLINICAL CHARACTERISTICS OF PEANUT ALLERGY AND THE DIAGNOSTIC ACCURACY OF THE SPECIFIC IgE TO Ara h 2].

BACKGROUND: This study aimed to evaluate the clinical accuracy of specific IgE (sIgE) to Ara h 2 in the diagnosis of peanut allergy (PA). We also investigated the prevalence of complications with other nut allergies in PA patients. METHODS: The Ara h 2-sIgE titer was examined in patients with positive results for sIgE to peanut from April 2014 to March 2015. The presence or absence of PA was diagnosed based on an oral food challenge or a convincing clinical history. The characteristics of 217 patients (including 90 PA patients) were retrospectively evaluated. RESULTS: At ≥0.35UA/mL, Ara h 2 showed 85.6% sensitivity in the diagnosis of PA. At the clinically-designated positive cut-off value (≥4.0UA/mL), the positive predictive value was 93.1% and the specificity was 96.9%. However, the Ara h 2-sIgE levels were not correlated with the threshold dose or the severity of the symptoms that were provoked in the peanut challenge (n=42). Nine (10%) of the PA patients also had allergies to other tree nuts. CONCLUSION: The re-evaluation of the clinically-designated positive Ara h 2-sIgE cut-off value revealed that the cut-off value was appropriate. The differential diagnosis of tree nut allergies was suggested to be important in PA patients.

Surveillance of the use of adrenaline auto-injectors in Japanese children.

BACKGROUND: The appropriate usage of an adrenaline auto-injector (AAI, Epipen®) is a key aspect of patient and social education in the management of anaphylaxis. However, although AAIs are being prescribed increasingly frequently, there are few reports on their actual use. METHODS: The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which AAIs were used. Two hundred and sixty-six cases were collected from March 2014 to March 2016. RESULTS: The cases included 240 events of immediate-type food allergies caused by cow's milk (n = 100), hen's egg (n = 42), wheat (n = 40), and peanuts (n = 11). Exercise-related events were reported in 19 cases; however, the diagnosis of food-dependent exercise-induced anaphylaxis with a specific causative food was only made in 4 cases (wheat, n = 2; fish, n = 1; squid, n = 1). The frequent reasons for the causative intake included programmed intake (n = 48), failure to check the food labeling (n = 43), and consuming an inappropriate food (n = 26). AAIs were used at schools or nurseries in 67 cases, with school or nursery staff members administering the AAI in 39 cases (58%). On arriving at the hospital, the symptom grade was improved in 71% of the cases, while grade 4 symptoms remained in 20% of the cases. No lethal cases or sequelae were reported. CONCLUSIONS: AAIs were used effectively, even by school teachers. The need to visit a hospital after the use of an AAI should be emphasized because additional treatment might be required.

Ipragliflozin, a sodium glucose co-transporter 2 inhibitor, reduces intrahepatic lipid content and abdominal visceral fat volume in patients with type 2 diabetes.

OBJECTIVE: We recently investigated the effect of ipragliflozin, a sodium glucose co-transporter-2 inhibitor (SGLT-2I), in Japanese patients with type 2 diabetes by a 24-week. SGLT-2Is also have an anti-obesity effect, and reduction of body fat has been demonstrated by indirect methods. However, evaluation of the effect on the total visceral fat volume and intrahepatic lipid content has not been performed. RESEARCH DESIGN AND METHODS: We measured the abdominal subcutaneous fat volume (SFV) and visceral fat volume (VFV) by whole abdominal CT scanning, the intrahepatic lipid (IHL) content by proton magnetic resonance spectroscopy (1H-MRS), and the fat mass index (FI) and appendicular skeletal mass index (ASMI) by dual X-ray absorptiometry (DXA) in 20 patients from our previous study. RESULTS: Administration of ipragliflozin at 50 mg/day for 24 weeks significantly reduced SFV, VFV, and IHL. FI and ASMI were also significantly decreased. Changes of VFV and IHL content at 12 weeks were significantly correlated with the change of HbA1c, but no correlation was observed at 24 weeks. CONCLUSION: These findings demonstrate that ipragliflozin decreases visceral and hepatic fat, with improvement of glycemic control possibly being attributable to these changes at least up to 12 weeks.