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Abstract We previously reported in the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A) that alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the progression of carotid atherosclerosis in subjects with type 2 diabetes and no history of cardiovascular disease. This extension study of the SPEAD-A trial investigated whether early alogliptin initiation improved long-term cardiovascular outcomes. The SPEAD-A trial randomized 341 subjects with type 2 diabetes to either alogliptin or conventional treatment to investigate the effects of alogliptin on atherosclerosis. All subjects who completed that trial were eligible for this prospective, observational cohort study. The primary endpoint was the first occurrence of a major cardiovascular event, defined as death due to any cause, acute myocardial infarction, or stroke. During the 520-week follow-up period, composite primary outcome events occurred in only a few subjects in each group [8 (5.4%) in the alogliptin group and 9 in the conventional treatment group (5.9%)]. There were no significant differences in the incidence rate of the primary outcome between the two groups. Post hoc Poisson regression analysis showed no significant difference between the two groups in the incidence rate of composite recurrence events for the same outcomes as the primary endpoint. On the other hand, this incidence rate was significantly lower in subjects who received DPP-4 inhibitors before an initial cardiovascular event than in those who did not (5.8 vs. 13.3 per 1000 person-years, respectively, p = 0.04). Early initiation of alogliptin was not associated with a reduced risk of composite cardiovascular disease, which could be attributed to fewer events and/or the addition of DPP-4 inhibitors during the follow-up period.

ABSTRACT Aims/Introduction To investigate whether the COVID‐19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions Our data suggest that glycemic control did not deteriorate during the COVID‐19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.

Abstract Background This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. Methods This was a prospective observational 2-year extension study of the “Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)” trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. Results The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (− 0.067 mm, standard error 0.009, p

Abstract Background This study investigated the sex differences in the risk of end‐stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. Methods This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. Results During a median follow‐up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02–1.75; p = .034) and death (HR 1.64; 95% CI 1.24–2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo‐ and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. Conclusions In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

ABSTRACT Aims/Introduction Few studies have investigated the renoprotective effect of glucagon‐like peptide‐1 (GLP‐1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. Materials and Methods Dulaglutide (group A) and non‐dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin‐to‐creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. Results In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score‐adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m2, HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m2, and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro‐albuminuria and/or concomitant SGLT2 inhibitor use. Conclusions Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.

Background: Bifidobacterium breve is an obligate anaerobic gram-positive bacillus mainly found in the gastrointestinal tract of human infants. Few cases of necrotizing fasciitis caused by B. breve have been reported. Case presentation: A 42-year-old Japanese man with type 2 diabetes mellitus, obesity, cellulitis of the back, and subcutaneous abscess of the right inguinal region presented with rapidly developing erythema, swelling and severe pain in the right inguinal region. Computed tomography showed widespread gas in the right leg region. Cultures of blood and a swab of the wound abscess grew gram-positive bacilli. Mass spectrography and 16 S rDNA analysis confirmed the gram-positive bacilli as B. breve. The patient recovered following extensive debridement and antibacterial therapy. Conclusion: Unidentified necrotizing fasciitis can be caused by B. breve, especially in compromised hosts.

We report the first case of immune complex type hemolytic anemia by initial micafungin administration that was given as prophylaxis to a 42-year-old Japanese man receiving chemotherapy for primary amyloidosis. The few cases found in the literature were associated with secondary administration causing immune hemolytic attacks. Despite its rarity, the present case calls for increased awareness of micafungin-induced hemolytic anemia upon initial administration.

Abstract The biaxially symmetric column induces torsional moment owing to the bending–torsion interaction when the top of the column is given horizontal displacement in the two directions of the principal axes of the cross section and the rotation of the column ends around the axes is constrained. Hence, horizontal ground motions in two directions can cause non‐negligible torsional vibration in a high‐rise building owing to autoparametric resonance. To investigate this phenomenon, in this study, we focus on a single‐story structure with an aggregated column, which is a model for columns or core structures in tall buildings and is assumed to be an elastic Euler beam; subsequently we derive the equations of motion under horizontal ground motions in two directions. The resonance condition in the torsional direction is also investigated. Time‐series response analyses are performed for input ground motions of harmonic waves, white noise, acceleration records of prior earthquakes, and a long‐period design wave, and the relationship between the ratio of two translational natural frequencies and the increase in maximum responses is explained. The results demonstrate that the absolute acceleration response to the long‐period design wave could increase by more than 50% in the worst‐case scenario.

Abstract Aims/Introduction Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients’ BMI levels. Materials and methods OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD‐treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI. Results Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase‐4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI 35 kg/m2 after BGs and sodium–glucose cotransporter 2 inhibitors . Conclusions DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.

Non-alcoholic fatty liver disease (NAFLD) is an important common comorbidity in individuals with type 2 diabetes (T2DM). Although some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on NAFLD, the efficacy of once-weekly semaglutide has not been established. This was a subanalysis of the SWITCH-SEMA 1 study, a multicenter, prospective, randomized, parallel-group trial comparing switching from liraglutide or dulaglutide to once-weekly semaglutide in subjects with T2DM (SWITCH) versus continuing current GLP-1RAs (Continue) for 24 weeks. This subanalysis consisted of participants who were suspected to have NAFLD [fatty liver index (FLI) ≥ 30]. In total, 58 participants met the criteria of this subanalysis. There were no statistical differences in baseline characteristics between the SWITCH (n = 31) and Continue groups (n = 27). FLI significantly improved during treatment in the SWITCH group (68.6 to 62.7) but not in the Continue group (71.1 to 72.3) (p < 0.01). The improvement of FLI in the SWITCH group was greater in switching from dulaglutide to semaglutide and significantly correlated with older age (p = 0.016) and lower baseline FLI (p < 0.01). The multiple linear regression analysis revealed that the switch from dulaglutide was associated with an improvement in FLI (p = 0.041). Switching from conventional GLP-1RAs to once-weekly semaglutide might be beneficial for individuals with NAFLD complicated with T2DM.

The Hybrid Emergency Room System (HERS) allows clinicians to perform life-saving procedures without having to transfer patients. Several studies have reported the effectiveness of the HERS in the treatment of blunt trauma patients. However, the use of a hybrid emergency room (ER) for the treatment of penetrating cardiac injuries, including impalement injuries, has not been reported. We present the case of a patient with cardiac impalement injury that was diagnosed via computed tomography (CT) and was managed via extracorporeal membrane oxygenation (ECMO) in the hybrid ER and via surgery in the operating room. A 55-year-old man was transferred to our hybrid ER due to a penetrating wood injury through the right thoracic region. The patient had unstable vital signs. A CT scan revealed a pericardial effusion, right lung contusion, and bilateral pneumothoraxes. There were no signs of hemothorax or aortic injury. Veno-arterial-ECMO was performed in preparation for surgery. The patient was then transferred to the operating room. Pericardiotomy and cardiac repair were performed, and the ECMO was discontinued postoperatively. The patient was discharged on postoperative day 10 without complications. The hybrid ER allows rapid CT examination without relocation. Thus, it facilitates the formation of a timely and effective treatment plan. This report documents the successful management of a cardiac impalement injury in the HERS.

Abstract Aims/Introduction To identify the effect of combination therapy with a dipeptidyl peptidase‐4 inhibitor and a sodium–glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase‐4 inhibitor to a sodium–glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. Materials and Methods A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel‐group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C‐peptide (CPR) divided at baseline by the median. Results ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (−29.2 ± 28.3 vs −20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group (P

Abstract Aims/Introduction We recently reported the beneficial effect of the combination of sodium–glucose cotransporter 2 inhibitor and dipeptidyl peptidase‐4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis. Materials and Methods The CALMER study was a multicenter, open‐label, prospective, randomized, parallel‐group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated. Results All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2–82.7%, P

Abstract Objectives Cardiovascular disease remains the most common cause of death in patients with type 2 diabetes mellitus. Because periodontitis is a risk factor of cardiovascular disease, identification of risk factors of periodontitis is valuable to control periodontitis effectively. The purpose of this study was to examine the association of education and household income with periodontal status in patients with type 2 diabetes mellitus. Methods Participants were 2,436 patients (59.8% male, aged 29–93 years) with type 2 diabetes mellitus from 27 medical clinics. Participants' medical records and information about education, household income, general health status, and health behaviors were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses and ordered logistic regression analyses were conducted to examine the association of periodontal parameters with education and household income after adjusting for age, sex, general health status, and health behaviors. Results Multiple linear regression analysis showed that mean probing pocket depth was not significantly associated with education and household income. Ordered logistic regression analyses showed statistically significant odds ratios (ORs) of junior high school (reference: university) for the tertiles of the percentage of sites with bleeding on probing (OR: 1.42; 95% confidence interval [CI]: 1.11–1.81), percentage of mobile teeth (OR: 1.58; 95% CI: 1.24–2.03), and number of teeth present (OR: 0.51; 95% CI: 0.39–0.65), and statistically significant odds ratios of high school (reference: university) for the tertiles of the percentage of mobile teeth (OR: 1.27; 95% CI: 1.06–1.51) and number of teeth present (OR: 0.74; 95% CI: 0.62–0.88), but not household income. Conclusions These results suggest that low education is one of the important predictors of poor periodontal status in patients with type 2 diabetes mellitus. It is important to provide targeted interventions including periodontal education in junior high school.

Background: We previously conducted a pilot randomized controlled trial “the MASTER study” and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. Methods: We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. Results: SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. Conclusions: Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.

Abstract Background Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. Methods The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. Results In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (– 109.3 [– 184.3, – 34.3] (mean change [95% CI] cm/s, p = 0.005; – 98.3 [– 172.6, – 24.1] cm/s, p = 0.010; – 104.7 [– 177.0, – 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. Conclusions Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html )

Abstract Background This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT). Methods This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period. Results In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (− 0.132 mm, SE 0.007; − 0.163 mm, SE 0.013; − 0.170 mm, SE 0.020, respectively) and the control group (− 0.140 mm, SE 0.006; − 0.190 mm, SE 0.012; − 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (− 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (− 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (− 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups. Conclusions/interpretation No IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population. Clinical Trial Registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).

Abstract Aims/Introduction To assess the prevalence of diabetic polyneuropathy (DPN)‐related sensory symptoms/signs and associated factors in patients with polyneuropathy, considering non‐linear effects for numerical variables. Materials and Methods A cross‐sectional survey of patients with type 2 diabetes mellitus from 17 primary care clinics across Japan was carried out. DPN and DPN‐related sensory symptoms/signs were diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria. Results Of the 9,914 patients with type 2 diabetes mellitus in this study, 2,745 had DPN and 1,689 had DPN‐related sensory symptoms/signs (61.5% of patients with DPN). There were significant correlations between DPN‐related sensory symptoms/signs and smoking status (odds ratio 2.04 for current and 1.64 for former; P

Hippocampal infarction is relatively rare. Many different diseases can mimic hippocampal infarction including transient global amnesia, Alzheimer’s disease, epilepsy, encephalitis, and encephalopathies. An 89-year-old man was transported to our hospital for altered consciousness. Diffusion-weighted magnetic resonance imaging revealed slightly intense signals in the hippocampus with a mildly decreased apparent diffusion coefficient. Serial magnetic resonance imaging revealed features of hippocampal infarction. Symptoms and cognitive function gradually improved with rehabilitation, and he was transferred to a rehabilitation facility on Hospital Day 38. Hippocampal infarction is rare in patients with altered mental status, but should be considered when magnetic resonance imaging shows findings suggestive of this condition. Other differential diseases should be ruled out by serial magnetic resonance imaging and observation of the clinical course.

Introduction Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD.Research design and methods Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk.Results Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of 5 and 2.5–5 mL/min/1.73 m2/year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m2/year compared with those with a minor change in UACR and eGFR.Conclusions Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes.

Background: We investigated the association between various food groups and obesity in Japanese patients with type 2 diabetes. Methods: 2070 patients with type 2 diabetes who attended 26 diabetes clinics throughout Japan were analyzed and were divided into obese and non-obese groups. Intakes of food groups determined by a food frequency questionnaire were compared. Odds ratios for obesity for quartiles of individual food groups were calculated using a logistic regression model. Results: Non-obese patients consumed a larger variety of food groups than obese patients, with the diets of non-obese individuals closer to the traditional Japanese diet characterized by fish, seaweed, and soybeans/soy products. Among 21 food groups, low vegetable intake and high sweets intake were the most strongly associated with obesity in both men and women. Low intake of both fruits and vegetables and the combination of high intake of sweets and low intake of fruits were associated with obesity. Conclusions: Food groups and their combinations that were strongly associated with obesity in Japanese patients with type 2 diabetes were identified. Our findings also suggested an inverse association between the traditional Japanese diet and obesity.

Abstract Aims/Introduction The prevalence and risk of vaginal candidiasis before and after initiating sodium–glucose cotransporter 2 (SGLT2) inhibitors, although some clinical trials have been carried out, have not been adequately shown in real‐world practice. We investigated the incidence of vaginal Candida colonization and symptomatic vaginitis, and the clinical risk factors including diabetic microvascular complications. Materials and Methods The participants were 114 women with type 2 diabetes who were free of vaginitis symptoms and started SGLT2 inhibitors. Vaginal candidiasis tests through self‐administered swabs were carried out at baseline, 6 and 12 months. Results Before starting SGLT2 inhibitors, 17 participants (14.9%) had positive vaginal Candida colonization. Younger age and the presence of microangiopathy were significantly associated with the positive colonization in multivariate analysis. Among all participants, 23 (20.2%, 8 because of vaginitis and 15 for other reasons) discontinued SGLT2 inhibitors before reaching the 6‐month test. Of 65 participants who were negative for Candida at baseline and received the 6‐month test, 24 (36.9%) converted to a positive culture, and multivariate analysis showed older age as an independent risk for developing Candida colonization. There were 18 participants (15.8%) who developed symptomatic vaginitis, and they showed similar characteristics to the 24 participants. Most of those with negative cultures at 6 months showed negative results at 12 months and vice versa. Conclusions The rates of developing positive colonization and symptomatic vaginitis after starting SGLT2 inhibitors appear to be higher in real‐world practice than the rates of 31% and 5–10% in clinical trials, respectively. Risk factors of vaginal Candida colonization might be different before and after taking SGLT2 inhibitors.

A typical proton CT (pCT) detector comprises a tracking system, used to measure the proton position before and after the imaged object, and an energy/range detector to measure the residual proton range after crossing the object. The Bergen pCT collaboration was established to design and build a prototype pCT scanner with a high granularity digital tracking calorimeter used as both tracking and energy/range detector. In this work the conceptual design and the layout of the mechanical and electronics implementation, along with Monte Carlo simulations of the new pCT system are reported. The digital tracking calorimeter is a multilayer structure with a lateral aperture of 27 cm × 16.6 cm, made of 41 detector/absorber sandwich layers (calorimeter), with aluminum (3.5 mm) used both as absorber and carrier, and two additional layers used as tracking system (rear trackers) positioned downstream of the imaged object; no tracking upstream the object is included. The rear tracker’s structure only differs from the calorimeter layers for the carrier made of ∼200 μm carbon fleece and carbon paper (carbon-epoxy sandwich), to minimize scattering. Each sensitive layer consists of 108 ALICE pixel detector (ALPIDE) chip sensors (developed for ALICE, CERN) bonded on a polyimide flex and subsequently bonded to a larger flexible printed circuit board. Beam tests tailored to the pCT operation have been performed using high-energetic (50–220 MeV/u) proton and ion beams at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. These tests proved the ALPIDE response independent of occupancy and proportional to the particle energy deposition, making the distinction of different ion tracks possible. The read-out electronics is able to handle enough data to acquire a single 2D image in few seconds making the system fast enough to be used in a clinical environment. For the reconstructed images in the modeled Monte Carlo simulation, the water equivalent path length error is lower than 2 mm, and the relative stopping power accuracy is better than 0.4%. Thanks to its ability to detect different types of radiation and its specific design, the pCT scanner can be employed for additional online applications during the treatment, such as in-situ proton range verification.

We aimed to analyze the association between dietary iron intake and obesity assessed by BMI after adjustment for nutrient intake (macronutrients and fiber) and food groups. The study design was cross-sectional. Patients with type-2 diabetes (n = 1567; 63.1% males; mean age 62.3 ± 11.6 years) were included in the study. To assess diet, consumption of typical food groups was determined by a food frequency questionnaire. Obesity was defined as BMI ≥ 25 kg/m2. We performed a binary regression analysis between quartiles of iron intake and obesity by quartiles of age group. A direct linear association was found for the highest quartile of iron intake and obesity in the younger age group of 30 to 54 years (OR = 3.641, 95% CI = 1.020–12.990; p trend = 0.011). Multivariate analysis using food groups as opposed to nutrients revealed a positive trend for obesity in the younger age group after adjusting for lifestyle factors, energy intake and bean and vegetable intake (p trend = 0.023). In all participants, an inverse association was observed before adjustment by vegetable intake (OR = 0.453, 95% CI = 0.300–0.684; p trend = 0.001). Higher iron intake was associated with obesity independent of macronutrient and fiber intake but only in the youngest quartile of age group examined.

A 77-year-old man presented to the emergency room with a 1-month history of persistent low back pain with the absence of vital sign abnormalities. On several previous orthopedic surgery clinic visits, pathological back pain had not been considered and pain killers had been prescribed because he had low back pain due to lumbar spinal canal stenosis. He was admitted to the intensive care unit for infectious spondylodiscitis and infective endocarditis with disseminated abscess caused by methicillin-resistant Staphylococcus aureus . Shock refractory tachyarrhythmia could not be managed with antiarrhythmic agent in the intensive care unit. Intractable low back pain and persistent tachyarrhythmia were adequately managed by pain control with fentanyl in the intensive care unit. Infectious spondylodiscitis and infective endocarditis were effectively managed with anti–methicillin-resistant Staphylococcus aureus drugs, initially in rotational usage, but the patient died of extended-spectrum beta-lactamase-producing Escherichia coli pneumonia on day 50 of hospitalization. Infectious spondylodiscitis should have been considered for persistent low back pain with hemodialysis, fever, and a history of device implantation. Pain management may be necessary for persistent tachycardia that proves unresponsive to usual antiarrhythmic medications.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease causing renal cysts. Reports on kidney cyst infection in children are rare despite cyst infections being important complications of ADPKD. Here, we report a case of a child without any medical history who had a urinary tract infection with sepsis at 7 months. Leukocyturia persisted despite antibiotic therapy because the infection was treatment-resistant. Initial ultrasound and contrast computed tomography were inconclusive because cysts could not be detected clearly, and a family history of renal cysts was not determined. Subsequently, history of paternal renal cysts, thick walls in infectious cystic lesions on diffusion-weighted magnetic resonance imaging (MRI), and multiple small lesions with high signals on T2-weighted imaging in both kidneys became apparent. Upon diagnosis of ADPKD with cyst infection, antibiotic therapy was switched from cefotaxime to trimethoprim/sulfamethoxazole to achieve better cyst penetration, which successfully resolved the infection. In this patient, MRI was effective for clear visualization and diagnosis of infectious lesions and small cysts in undiagnosed ADPKD with cyst infection. Administering antibiotics with better cyst penetration is important. Trimethoprim/sulfamethoxazole is an option for use in children. This is the first case report that describes ADPKD with cyst infection in an infant in detail.

Abstract The short‐form glucose‐dependent insulinotropic polypeptide (GIP) (1–30) is released from islet alpha cells and promotes insulin secretion in a paracrine manner in vitro. However, it is not well elucidated how GIP (1–30) is involved in glucose metabolism in vivo, since a specific assay system for GIP (1–30) has not yet been established. We first developed a sandwich enzyme‐linked immunosorbent assay (ELISA) specific for GIP (1–30) by combining a novel antibody specific to the GIP (1–30) C terminus with the common antibody against GIP N terminus. Then, we explored cross‐reactivities with incretins and glucagon‐related peptides in this ELISA. GIP (1–30) amide, but not GIP (1–42), GLP‐1, or glucagon increased absorbance in a dose‐dependent manner. We next measured plasma GIP (1–30) concentrations in nondiabetic participants (ND) during a 75‐g oral glucose tolerance test or cookie meal test (carbohydrates 75 g, lipids 28.5 g, proteins 8.5 g). Both glucose and cookie load increased GIP (1–30) concentrations in ND, but the increases were much lower than those of GIP (1–42). Furthermore, the DPP‐4 inhibitor significantly increased GIP (1–30) concentrations similarly to GIP (1–42) in ND. In conclusion, we for the first time developed an ELISA specific for GIP (1–30) and revealed its secretion in ND.

Objective: We recently observed a greater increase in plasma levels of bioactive glucose-dependent insulinotropic polypeptide (GIP) than glucagon-like peptide 1 (GLP-1) using the receptor-mediated bioassays in the subjects with normal glycemic tolerance (NGT) treated with dipeptidyl peptidase 4 (DPP-4) inhibitors, which may be unappreciated using conventional enzyme-linked immunosorbent assays (ELISAs) during oral glucose tolerance test. Thus, we determined incretin levels in addition to glucagon level using the bioassays in type 2 diabetes mellitus (T2DM) subjects with or without treatment of DPP-4 inhibitor, to evaluate whether these assays can accurately measure bioactivity of these peptides.Methods: We performed single meal tolerance test (MTT) by using a cookie meal (carbohydrate 75.0 g, protein 8.0 g, fat 28.5 g) in the subjects with NGT (n = 9), the subjects with T2DM treated without DPP-4 inhibitor (n = 7) and the subjects with T2DM treated with DPP-4 inhibitor (n = 10). All subjects fasted for 10–12 h before the MTT, and blood samples were collected at 0, 30, 60, and 120 min. We used the cell lines stably cotransfected with human-form GIP, GLP-1 or glucagon receptor, and a cyclic adenosine monophosphate–inducible luciferase expression construct for the bioassays. We measured active GIP, active GLP-1, and glucagon by the bioassays. To evaluate the efficacy of bioassay, we measured identical samples via ELISA kits.Results: During the single MTT study, postprandial active GIP bioassay levels of T2DM with DPP-4 inhibitor treatment were drastically higher than those of NGT and T2DM without DPP-4 inhibitor, although the DPP-4 inhibitor-treated group showed moderate increase of active GIPELISA and active GLP-1bioassay, while active GLP-1bioassay levels of T2DM subjects without DPP-4 inhibitor were comparable to those of NGT subjects. During the serial MTT, administration of DPP-4 inhibitor significantly increased active GIPbioassay levels, but not active GLP-1bioassay.Conclusions: In comparison to conventional ELISA, receptor-mediated bioassay reflects dynamic change of GIP polypeptide by DPP-4 inhibitor treatment in subjects with type 2 diabetes.

To investigate the association between dietary energy density (DED) and obesity in people with type 2 diabetes mellitus. Moreover, we compared the strength of the associations of DED with intake of energy and macronutrients in terms of obesity as well as nutritional factors that have long been used for medical nutritional therapy. Cross-sectionally investigated were 1615 outpatients with type 2 diabetes who attended 26 clinics nationwide with diabetes specialists. Odds ratios (ORs) were calculated for the association between obesity and DED, energy, and macronutrients by quintile categories and a 1 SD increment with adjustment for potential confounders. β coefficients were calculated for the association between body mass index (BMI) and each nutritional factor by 1 SD increments in nutritional values. Multi-adjusted OR for obesity between extreme quintiles of DED was 2.99 (95% confidence interval (95% CI): 2.01–3.12). Conversely, the ORs did not differ significantly according to the quintiles of other nutrient factors. Multi-adjusted β coefficient of BMI per 1 SD according to DED was far higher than those of other nutrient factors (β coefficient 0.65, 95% CI: 0.41–0.88). These findings indicated that DED in persons with type 2 diabetes was positively associated with BMI and the prevalence of obesity. DED was also much more potently associated with obesity and BMI than nutritional indicators such as intake of energy or macronutrients.

Background: In order to provide effective dietary guidance, it is necessary to consider dietary intake, which can change over time. This study analyzed changes in the diet of Japanese patients with type 2 diabetes over a 20-year period. Methods: We compared the results of two dietary surveys that used the food frequency questionnaire format. The first was conducted in 1996 by the Japan Diabetes Complications Study (JDCS) (n = 1509; males 53.3%), and the second in 2014–2018 by the Japan Diabetes Clinical Data Management Study (JDDM) (n = 1145; males 65.6%). Both are nationwide representative registries of outpatients with type 2 diabetes in Japan. Results: Over a 20-year period, both men and women with type 2 diabetes had a significant increase in body mass index (BMI). Nonetheless, there was only a small change in energy intake. Conversely, there was a significant increase in fat intake and thus in the fat-to-energy ratio. With regard to food groups, there was a significant increase in meat intake and a decrease in the intake of fish, soybeans/soy products, vegetables, and fruits, with a particularly significant decrease in vegetables. Conclusions: Even in Japan, an industrialized country with a stable socioeconomic environment, there were many significant changes in the dietary intake of patients with type 2 diabetes over the 20-year period.

Abstract The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule‐containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule‐containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May‐Giemsa staining. The patients were classified into two groups, the granule‐containing myeloma (GM) and nongranule‐containing myeloma (non‐GM) groups, depending on the proportion of myeloma cells that contained granules (cut‐off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non‐GM group (t‐test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow‐up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non‐GM group; 4‐year OS of the GM and non‐GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule‐containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

The aim of this study was to investigate the association between habitual dietary intake for patients with diabetes and the content of family support for medical nutritional therapy (MNT). Analyzed were 289 Japanese with type 2 diabetes (men, 58.5%; mean age, 62.0 years; mean HbA1c, 53.4 mmol/mol) who completed the Food Frequency Questionnaire and Diabetes Family Behavior Checklist (DFBC). Relationships of mean values for food group intake to DFBC responses regarding MNT were examined using multivariate analysis of covariance. Positive response to “Praise for following diet” was associated with lower sweets intake (none: 60.1 g/day; ≥once monthly: 50.9 g/day, p = 0.038) and higher seasoning intake (none: 21.6 g/day, ≥once monthly: 24.1 g/day, p = 0.046). Energy intake was higher with positive responses to “Eat at the same time that you do” (none: 1636 kcal/day, ≥once monthly: 1818 kcal/day, p = 0.038). “Nags about not following diet” was associated with higher fish (none: 68.7 g/day, ≥once monthly: 78.7 g/day, p = 0.042) and salt intake (none: 8.3 g/day, ≥once monthly: 9.0 g/day, p = 0.014). Eating foods not part of the diabetic diet (none: 218.4 g/day, ≥once monthly: 246.9 g/day, p = 0.014) resulted in a higher vegetable intake. In females, significant differences in relationships in the overall analysis were reversed. Our results clarified relationships between types of family support of patients with type 2 diabetes and their dietary intake and the importance of sex differences for more effective MNT.

Eccentric distribution of stiffness, damping, and mass of a structure, and spatially non-uniform ground motion input to a long or large base mat of a structure are well-known causes of torsional response. We have discovered that the torque generated by horizontal displacement and perpendicular inertial force, which we call the Q-Δ effect, can be a cause of torsional response. We formulated the equation of motion of a single finite-size mass-linear elastic shear and torsion spring model and clarified the resonance condition of the torsional response to sinusoidal ground acceleration. Time-history response analysis verified that the torsional response forms beat and the maximum torsional response of the simulation result agrees with that theoretically predicted. Further time-history response analysis conducted of white noise ground acceleration showed that even one-directional white noise ground acceleration can induce torsional response in a linear elastic system without any structural eccentricity.

BACKGROUND:According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. METHODS:This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. RESULTS:In the 2-year baseline analysis, the cumulative prevalence of -20%, -30%, -40%, and -53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following -53%, -40%, -30%, and -20% changes in eGFR during the 2-year baseline period were 22.9 (11.1-47.3), 12.8 (6.9-23.7), 8.2 (4.3-15.5), and 3.9 (2.2-7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8-81.9), 18.4 (7.6-44.7), 12.8 (5.2-32.2), and 5.4 (2.3-12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. CONCLUSIONS:Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease.

In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity.We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to

The flow inside the two-dimensional semi-open-type nozzle for ship propulsion equipment, directly driven by high-pressure gas was investigated experimentally. The flow was unsteady and the gas and water phases clearly separated. We found that these waves appear on the interface for continuous gas ejection. It was clarified that waves play an important role in the pressure distribution. Intermittent gas ejection was also tried. The thrust itself decreases compared with continuous gas ejection, but propulsion efficiency, considering the gas ejection duration is increased. The flow patterns for intermittent gas ejection were also clarified.

To evaluate the prognostic impact of monosomal karyotype on post-remission outcome in acute myeloid leukemia, we retrospectively analyzed 2,099 patients who had achieved complete remission. Monosomal karyotype was noted in 73 patients (4%). Of these, the probability of overall survival from first complete remission was 14% at four years, which was significantly lower than that reported in patients without monosomal karyotype, primarily due to a high relapse rate (86%). Monosomal karyotype remained significantly associated with worse overall survival among patients with unfavorable cytogenetics or complex karyotype, and even in patients who underwent allogeneic hematopoietic cell transplantation during first complete remission. These findings confirm that monosomal karyotype has a significantly adverse effect on post-remission outcome in patients with acute myeloid leukemia treated with and without allogeneic hematopoietic cell transplantation in first complete remission, emphasizing the need for the development of alternative therapies for this patient population.