Function In Japanese Patients Research Articles

Improvement effects of tapinarof on the skin barrier function in Japanese patients with atopic dermatitis

Background: Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. Tapinarof has been shown to be efficacious and have acceptable safety profile in the treatment of atopic dermatitis (AD).Objective: We sought to evaluate the improvement effect of tapinarof on skin barrier function in patients with AD.Methods: This was an open-label, uncontrolled, single-center study. Japanese patients aged ≥20 years with AD (N = 30) were included in this study. Patients applied tapinarof cream 1% once daily to the target areas on the volar forearm for 8 weeks. The primary endpoints were changes from baseline in stratum corneum hydration (SCH) and transepidermal water loss (TEWL) at the target affected area at week 8.Results: The mean SCH value at the target affected area was 13.656 AU at baseline, 16.904 AU at week 4, and 16.423 AU at week 8. The SCH at the target affected area significantly increased from baseline to week 8, with a mean change of 2.826 AU (p = 0.0433). The mean TEWL value at the target affected area was 17.35 g/m2/hr at baseline, 10.01 g/m2/hr at week 4, and 9.52 g/m2/hr at week 8. The TEWL at the target affected area significantly decreased from baseline to week 8, with a mean change of −8.03 g/m2/hr (p < 0.0001). Clinical signs of AD at the target affected area were improved over time. No serious, severe, or treatment-related AEs were reported.Conclusion: Treatment with tapinarof led to an increase in SCH and a decrease in TEWL in patients with AD, indicating the potential improvement effect of tapinarof on skin barrier function.

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

BackgroundRenal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes.MethodsThis retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression.ResultsThe prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only.ConclusionsClinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

Increase in creatinine levels associated with niraparib maintenance therapy in ovarian cancer.

In Japan, Niraparib maintenance therapy for primary and recurrent ovarian cancer was approved in September 2020 and is expected to improve the prognosis of ovarian cancer. However, the safety of niraparib maintenance therapy in Japanese patients has not been fully evaluated. Patients with ovarian cancer (including fallopian tube and peritoneal cancer) treated with niraparib at Jichi Medical University Hospital from September 2020 to August 2022 were enrolled in this study. Patient background, starting dose, rates of interruption, reduction, or discontinuation, adverse events (AEs) during treatment, and estimated glomerular filtration rate (eGFR) trends were retrospectively analyzed. Twenty-nine patients received niraparib maintenance therapy during the study period, including 21 with primary cancer and 8 patients with recurrent cancer. Seventeen patients (58.6%) required dose interruptions and 16 patients (55.2%) required dose reductions. Only two patients (6.9%) discontinued treatment due to fatigue and nausea. The most frequent AE was creatinine increases in 18 patients (62.1%, all grades). Although eGFR levels decreased significantly after niraparib therapy compared to before niraparib therapy (59.3 vs. 50.3 mL/min/1.73 m2 , p < 0.001), the levels returned to pre-niraparib initiation levels after discontinuation of niraparib (64.6 vs. 64.6 mL/min/1.73 m2 , p = 0.96). Multivariate regression analysis showed that diabetes was independently associated with decreased eGFR (p = 0.013). Niraparib maintenance therapy frequently increased serum creatinine, but the change was reversible. Further studies are needed to determine the effects of niraparib on renal function in Japanese patients.

1553-P: Postprandial C-Peptide–to–Glucose Ratio Is Valuable in Assessing Beta-Cell Function in Japanese Patients with Type 2 Diabetes

Onset of type 2 diabetes (T2D) is based on the insulin secretion (loss of β-cell function) and resistance. Residual β-cell function is a key factor in achieving optimal glycemic control in T2D patients. Glucagon stimulates insulin, therefore glucagon stimulation test (GST) is a reliable marker for β-cell function. Fasting C-peptide (CPR) to glucose ratio (CPR[ng/ml] to glucose[mg/dl] x100; F-CPR-index) is used as a marker of insulin secretion. We evaluated the efficacy of postprandial CPR to glucose ratio (P-CPR-index) for evaluating β-cell function in T2D. Japanese T2D patients with inadequate glycemic control (HbA1c&amp;gt;7.0) were enrolled in the study (n=500, insulin therapy=283). HbA1c, fasting CPR and glucose, postprandial (120 min after breakfast) CPR and glucose were measured, and F-CPR-index and P-CPR-index were calculated. GST was performed as follows: 1mg of glucagon was injected intravenously, CPR was determined before and 6 min after injection, GSTΔCPR (CPR[6 min] - CPR[0 min]) was calculated. Factors correlated with GSTΔCPR were analyzed using simple and multiple stepwise regression analysis. P value&amp;lt;0.05 was defined as statistically different. F-CPR-index, P-CPR-index and GSTΔCPR were 1.60±0.95, 2.67±1.92 and 1.93±1.21, respectively. Simple regression analysis showed that GSTΔCPR was significantly correlated with age, height, body weight (BW), BMI, waist circumference, duration of diabetes, retinopathy, insulin therapy, urinary CPR, F-CPR-index and P-CPR-index. Multiple stepwise regression analysis revealed that independent factors contributing to GSTΔCPR were BW (β=0.336), duration of diabetes (β= −0.107), presence of retinopathy (β= −0.121), use of DPP-4i (β= −0.099), metformin (β= −0.109), SGLT2i (β= −0.108, p=0.002) and P-CPR-index (β=0.432)(R2=0.453). Our date demonstrated that P-CPR-index was valuable and simple method in assessing residual β-cell function with/without insulin therapy in daily clinical practice. Disclosure Y.Matsuhashi: None. T.Abe: None. T.Fujita: None. S.Mizushiri: None. S.Chikazawa: None. M.Daimon: None.

Characteristic association of symbol coding test score with occupational function in Japanese patients with schizophrenia.

Studies showed that cognitive function affects occupational function in patients with schizophrenia. This study aimed to determine the effects of cognitive function on occupational function in Japanese patients with schizophrenia using the Brief Assessment of Cognition in Schizophrenia (BACS). Participants were 198 outpatients with schizophrenia or schizoaffective disorder (66 females; mean age 34.5 ± 6.8 years). Occupational function was assessed using the work subscale of the Life Assessment Scale for Mental Ill (LASMI-w). Multiple regression analysis was performed using the BACS as the independent variable and LASMI-w as the dependent variable. Furthermore, we divided the LASMI-w score into three groups, <11, 11-20, and >21, and performed a multinomial logistic regression analysis. Multiple regression analysis revealed that LASMI-w score was negatively associated with BACS composite score (β=-0.20, p < 0.01). Among the sub-items of the BACS, only the symbol-coding score showed a significant negative association (β=-0.19, p < 0.05). Multinomial logistic analysis showed that the better the composite and symbol coding scores, the smaller the impairment of the occupational function (composite score: β=2.39 between mild and moderate occupational impairments, p < 0.05; symbol coding score: β=2.44 between mild and severe impairments, p < 0.05). The occupational function of patients with schizophrenia was associated with overall cognitive function (composite score). In particular, the symbol coding score of the BACS was suggested to be related to work ability. These results might be useful in the assessment and training of cognitive rehabilitation aimed at employment support.

Validation and Functional Relevance of the Short Form of the Perceived Deficits Questionnaire for Depression for Japanese Patients with Major Depressive Disorder.

To validate the five-item version of the Perceived Deficits Questionnaire for Depression (PDQ-D-5) for assessing subjective cognitive function in Japanese patients with major depressive disorder (MDD) using data from the PERFORM-J study. A total of 518 Japanese outpatients diagnosed with MDD were assessed on severity of depressive symptoms, cognitive function, social and work function, and quality of life (QoL) over 6 months following initiation of antidepressant therapy. This post hoc analysis evaluated the internal consistency and convergent validity of the PDQ-D-5 in relation to the original PDQ-D-20. Correlations of scores on these measures were examined at each time point and over time. The same set of analyses was explored between PDQ-D-5 and the Patient Health Questionnaire-nine-item (PHQ-9), Montgomery-Asberg Depression Rating Scale (MADRS), Digit Symbol Substitution Test (DSST), five-level version of EQ-5D (EQ-5D-5L), Sheehan Disability Scale (SDS), and Work Productivity and Activity Impairment (WPAI) questionnaire. PDQ-D-5 scores showed good internal consistency. Strong positive correlations were observed between PDQ-D-5 and PDQ-D-20 at each time point (correlation coefficient: baseline, 0.94; month 1, 0.94; month 2, 0.96; month 6, 0.96) and over time (0.92) (all p < 0.0001). Longitudinally, there were positive correlations between PDQ-D-5 scores versus those on the PHQ-9, MADRS, and SDS. Similarly, negative correlations were noted between PDQ-D-5 scores and EQ-5D-5L and DSST scores to a variable degree. There were moderate positive correlations over time between PDQ-D-5 and all WPAI subscale scores except those on absenteeism. PDQ-D-5 scores rated in Japanese patients with MDD were found to adequately represent scores on the PDQ-D-20. The short version also showed associations with several measures of functional outcome, depression severity and QoL. This validates the PDQ-D-5 as a feasible and clinically reliable tool to assess subjective experience on cognition, which is applicable to time-limited consultations. UMIN000024320.

The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67).

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. 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. 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. Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.

120-OR: Hepatic Steatosis Is Inversely Associated with Improvement of Pancreatic Beta-Cell Function after Vertical Sleeve Gastrectomy in Patients with Type 2 Diabetes

Background: Improvement of beta-cell function is reportedly involved in the improvement of glucose tolerance and remission of diabetes after bariatric and metabolic surgery. However, the impact of this surgery on beta-cell function in Japanese patients is not clear. The objective of this study was to investigate the effect of this surgery on beta-cell function and the characteristics and factors related to changes in beta-cell function. Methods: We conducted a prospective study of patients with type 2 diabetes who underwent vertical sleeve gastrectomy. A 75-g OGTT was performed before and 1 year after this surgery. Glucose tolerance was evaluated using the area under the blood glucose curve (AUCglu) during the OGTT. Insulin secretion was evaluated by the insulin secretion-sensitivity index-2 (ISSI-2) and disposition index (DI) , and insulin sensitivity was estimated using the Matsuda index (MI) and HOMA-IR. Visceral fat and subcutaneous fat area were quantified by abdominal CT examination, and hepatic fat content was quantified using the MRI proton density fat fraction. Results: The mean age of 15 patients (6 females) was 41.9 ± 8.8 years. After 1 year of the surgery, BMI (Before 42.0±8.2 kg/m2, After 32.7±7.2 kg/m2; P &amp;lt; 0.01) , HbA1c, and AUCglu were significantly reduced. ISSI-2 and DI were significantly increased, with no significant changes in the MI or HOMA-IR. Changes in ISSI-2 and DI were inversely associated with hepatic fat content before the surgery (ISSI-2: r = -0.63, P &amp;lt; 0.05; DI: r = -0.59, P &amp;lt; 0.05) , but not with age, BMI, visceral fat area, AUCglu, ISSI-2, DI, MI or HOMA-IR before the surgery. Conclusion: Our results showed that beta-cell function was improved by vertical sleeve gastrectomy even in Japanese obese patients with type 2 diabetes. The degree of improvement in beta-cell function was associated with the degree of preoperative hepatic steatosis, suggesting that a hepatic-pancreatic association may exist. Disclosure A. Nakamura: Research Support; Kissei Pharmaceutical Co., Ltd., MSD, Nippon Boehringer Ingelheim, Taisho Pharmaceutical Holdings Co., Ltd. Y. Oe: None. M. Kusumi: None. H. Nomoto: None. H. Kameda: None. K. Cho: None. K. Ogawa: None. Y. Ebihara: None. T. Atsumi: Consultant; AbbVie Inc., AstraZeneca, MEDICAL &amp; BIOLOGICAL LABORATORIES CO., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Inc. Research Support; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly and Company, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Inc., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, UCB, Inc. H. Miyoshi: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kowa Company, Ltd., LifeScan, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. Speaker's Bureau; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Eli Lilly and Company, Kowa Company, Ltd., Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd.

Comparison of renal outcomes between sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists

AimsThis study aimed to clarify the differences in how sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1Ra) influence kidney function in Japanese patients with type 2 diabetes mellitus (T2DM). MethodsWe retrospectively built two databases of patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. We defined the renal composite outcome as either progression of albuminuria status and/or > 15% deterioration in estimated glomerular filtration rate (eGFR) per year. We used propensity score matching to compare patient outcomes after SGLT2i and GLP1Ra treatments. ResultsThe incidence of renal composite outcomes was significantly lower in SGLT2i-treated patients than in GLP1Ra-treated patients (n = 15[11%] and n = 27[20%], respectively, P = 0.001). Annual eGFR changes (mL/min/1.73 m2/year) between the two groups differed significantly (−1.8 [95 %CI, −2.7, −0.9] in SGLT2i-treated patients and − 3.4 [95 %CI, −4.6, −2.2] in GLP1Ra-treated patients, P = 0.0049). The urine albumin-to-creatinine ratio changed owing to a significant interaction between the presence or absence of a decrease in systolic blood pressure and the difference in treatments (P < 0.04). ConclusionRenal composite outcome incidence was lower in SGLT2i-treated patients than in GLP1Ra-treated patients.

Analysis of thyroid function in Japanese patients with coronavirus disease 2019.

Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.

Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia.

Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.

Relationship of continuous glucose monitoring-related metrics with HbA1c and residual \u03b2-cell function in Japanese patients with type 1 diabetes

The targets for continuous glucose monitoring (CGM)-derived metrics were recently set; however, studies on CGM data over a long period with stable glycemic control are limited. We analyzed 194,279 CGM values obtained from 19 adult Japanese patients with type 1 diabetes. CGM data obtained during stable glycemic control over four months were analyzed. CGM-related metrics of different durations “within 120, 90, 60, 30, and 7 days” were calculated from baseline. Time in range (TIR; glucose 70–180 mg/dL), time above range (TAR; glucose ≥ 181 mg/dL), and average glucose levels, but not time below range (TBR; glucose ≤ 69 mg/dL), strongly correlated with glycated hemoglobin (HbA1c) values (P < 0.0001). TBR correlated with glucose coefficient of variation (CV) (P < 0.01). Fasting serum C-peptide levels negatively correlated with glucose CV (P < 0.01). HbA1c of approximately 7% corresponded to TIR of 74% and TAR of 20%. The shorter the CGM period, the weaker was the relationship between HbA1c and CGM-related metrics. TIR, TAR, and average glucose levels accurately reflected HbA1c values in Japanese patients with type 1 diabetes with stable glycemic control. Glucose CV and TBR complemented the limitation of HbA1c to detect glucose variability and hypoglycemia. Stable glycemic control with minimal hypoglycemia depended on residual β-cell function.

The Association Between Hot Flashes and Renal Dysfunction After Androgen Deprivation Therapy With Radiotherapy in Japanese Patients With High-risk Prostate Cancer.

We investigated the changes in and characteristics of renal function in Japanese patients with high-risk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued. Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months. The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months. Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and high-risk PCa patients prior to ADT.

Effects of the number of hospitalizations on cognitive function in Japanese patients with stable schizophrenia.

The present study aimed to determine whether the number of hospitalizations in schizophrenia patients is associated with reduced cognitive performance, which may in turn imply that recurrences indirectly lead to a worsening in the disorder's progression. Cognitive performance in stable schizophrenia patients was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, on 30 patients who had not experienced any hospitalizations (G0), 57 patients who had experienced only one hospitalization (G1), 47 patients with two hospitalizations (G2), and 59 patients with three or more hospitalizations (G3). Significant differences in motor function and attention and processing speed were found between patients with G0 and those with G1. Significant differences in working memory and verbal fluency were found between patients with G1 and those with G2. Patients with G3 performed even more poorly in comparison with those with G1, showing deficits in verbal memory, working memory, executive function, and composite score. The patients with G3 displayed a greater range of impairment and demonstrated deficits in executive function compared with patients with G2. Finally, G2 and G3 performed more poorly than G0, with deficits in the various cognitive areas. The number of hospitalizations predicted cognitive performance, which suggests that relapse or recurrence may have a long-term neuropsychological impact. Prospective follow-up studies must be completed to explore this effect further because better treatment adherence may have a protective effect on neurocognitive function.

Psychometric properties of the Japanese version of the Kansas City Cardiomyopathy Questionnaire in Japanese patients with chronic heart failure

BackgroundHeart failure is a worldwide health problem that significantly affects patients’ physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ.MethodsUsing pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach’s α, and test–retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients’ clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved.ResultsAmong 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p < 0.001 for all, Jonckheere-Terpstra test). The physical limitations domain and CSS showed a moderate correlation (Spearman’s ρ = − 0.40 to − 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach’s standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test–retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3–4.2 points with intraclass correlation coefficients of 0.65–0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62–0.88.ConclusionsThe Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure.

Coefficient of Determination between Estimated and Measured Renal Function in Japanese Patients with Sarcopenia May Be Improved by Adjusting for Muscle Mass and Sex: A Prospective Study

Creatinine (Cr) levels are strongly affected by muscle mass, and the estimated glomerular filtration rate (eGFR), a measure based on serum creatinine (SCr), is often overestimated in patients with sarcopenia. To evaluate the coefficient of determination (R2) between eGFR and the actual measured value, we performed a linear regression analysis of a modified GFR (mGFR: measured Cr clearance × 0.715) and various renal function estimates adjusted for muscle mass in 19 patients with sarcopenia. The eGFR values based on SCr (eGFRcr) were higher than those based on mGFR, although a high R2 (0.704; p < 0.001) was found between these values. There was no deviation between eGFR based on serum cystatin C (eGFRcys) and mGFR, although the R2 value 0.691 was equivalent to that of eGFRcr. In the equation used to calculate eGFRcr not adjusted for body surface area (mL/min), muscle mass parameters obtained from bioelectrical impedance analysis were used instead of actual body weight to recalculate the eGFRcr. The R2 between this eGFRcr and mGFR did not improve, although there was less deviation. However, assuming that all patients were female by using female coefficients for all patients, the R2 between eGFRcr-fcc (eGFRcr with female coefficient correction) and mGFR improved and was the highest (0.808) on substitution of appendicular skeletal muscle mass. The correlation between eGFRcr-fcc and mGFR improved over eGFRcys when muscle mass was substituted for body weight in the equation used to estimate eGFR in patients with sarcopenia and sex differences were removed.

2347-PUB: Relationship between Aging and Effects of SGLT2 Inhibitors on Glucose and Lipid Metabolisms and Hepatic Function in Japanese Patients with Type 2 Diabetes

SGLT2 inhibitors (SGLT2is) have been found to improve blood glucose, HbA1c and triglyceride levels and also hepatic dysfunction in patients with type 2 diabetes. However, scarcely any studies have examined whether there are differences in the effects of SGLT2is according to patient age. In this study, we stratified the patients into 3 groups according to the age and investigated whether age influences the effects of SGLT2is on glucose and lipid metabolisms and hepatic function in these patients. The patients were stratified into the following 3 age groups: &amp;lt;50, 50 to 64, and ≥65 years. Five SGLT2is were administered for 6 months at the following doses: 2.5 mg/day luseogliflozin, 5 mg/day dapagliflozin, 20 mg/day tofogliflozin, 10 mg/day empagliflozin, and 100 mg/day canagliflozin. Blood samples were collected before and after the treatment to measure biochemical parameters. Significant decreases, compared to the baseline, of HbA1c, serum glucose and insulin, and HOMA-R were observed after the treatment with the SGLT2is in the &amp;lt;64 years age groups, but not the ≥65 years age group. With regard to the effects on lipid metabolism, increase in serum HDL cholesterol and decrease in LDL cholesterol/HDL cholesterol ratio were observed in the ≥65 years age group. In addition, hepatic function parameters improved significantly in the &amp;lt;64 years age groups, but to a lesser degree in the ≥65 years age group. The effects on BMI were not affected. The results revealed that some effects of SGLT2is were affected by aging. The SGLT2is improved glucose metabolism in the patients aged &amp;lt;64 years, but this effect was weaker in those aged ≥65 years. However, the SGLT2is led to a more anti-atherogenic serum lipid profile in patients aged ≥65 years than in those aged &amp;lt;65 years. In addition, it appears that the hepatic function-improving effect of SGLT2is decreases with age, especially in patients aged ≥65 years. The effects of SGLT2 inhibitors on BMI were not affected. Disclosure M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Natsume: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Oshida: None. T. Miyata: Research Support; Self; Bayer AG, Daiichi Sankyo Company, Limited.

SAT-358-Sodium glucose cotransporter 2 inhibitor, canagliflozin ameliorate liver function in Japanese patients with type 2 diabetes mellitus: Subgroup analyses of clinical trials

SAT-358-Sodium glucose cotransporter 2 inhibitor, canagliflozin ameliorate liver function in Japanese patients with type 2 diabetes mellitus: Subgroup analyses of clinical trials

Temporal trends in the prevalence of albuminuria and reduced eGFR in Japanese patients with type 2 diabetes.

Changes over time have been shown in renal manifestations in individuals with diabetes in the United States; however, whether the trends are shared across ethnicities is unknown. We conducted this single-center serial cross-sectional study to determine temporal changes in albuminuria and reduced kidney function in Japanese patients with type 2 diabetes. This study included adult Japanese patients with type 2 diabetes who first visited our institute between 2004 and 2013. Temporal changes during the 10years in the frequency of albuminuria ( ≥ 30mg/g creatinine) and reduced eGFR ( < 60mL/min/1.73m2) were analyzed using the univariate and multivariate logistic regression analyses and Granger causality test. 5331 Japanese patients with type 2 diabetes, 1892 women and 3439 men, with the mean age of 56 ± 13years, were studied. There was no change in the prevalence of albuminuria in the univariate analysis; however, a significantly decreasing trend was observed after adjustment for several covariates. On the other hand, patients with reduced eGFR significantly increased over time, although the statistical significance disappeared after adjustment for the covariates, including levels of serum uric acid and hemoglobin and use of renin-angiotensin inhibitors. The Granger causality test showed that time series for use of RAS inhibitors and BMI had a causative role in time series for reduced eGFR. In conclusion, prevalence of albuminuria decreased and that of reduced eGFR remained stable after adjustment for clinical characteristics in Japanese patients with type 2 diabetes during the last decade.

Chronic kidney disease is associated with physical impairment

BackgroundPhysical impairment or frailty due to sarcopaenia is common in patients with chronic kidney disease and those receiving dialysis. This study examined the association between muscle weakness and kidney function in Japanese patients with chronic kidney disease.MethodsA total of 23 stable outpatients were enrolled in the study. Several indices were used to assess muscle function; hand grip strength, isometric knee extension strength, Timed Up and Go test (TUG), and the short physical performance battery. The relationships between these indices and estimated glomerular filtration rate (eGFR) as a measure of kidney function were analysed statistically.ResultsPatients’ characteristics were as follows: mean age 73.9 years (standard deviation (SD) 13); 12 males, 11 females; body mass index (BMI) 22.5 kg/m2 (SD 3.2); serum creatinine (sCr) 4.6 mg/ dl (SD 3.7); estimated glomerular filtration rate (eGFR) 19.1 ml/min (SD 16). Their physical performance indices were: hand grip strength 20.8 kg (SD 7.9); isometric knee extension strength 19.1 kgf/kg (SD 10.6); TUG 14.9 s (SD 6.0); and short physical performance battery score 7.0 (SD 4.3). Multiple regression analysis adjusted for age revealed significant associations between isometric knee extension strength/body weight and eGFR (F [2,19] = 8.38, p = 0.002) and TUG and eGFR (F=4.98 [2,18], p = 0.02).ConclusionDeterioration in muscle function or maintenance of posture is associated with chronic kidney disease.LAY ABSTRACTFrailty due to sarcopaenia is common in patients with chronic kidney disease and those receiving dialysis. However, there is limited information available on the relationship between kidney function and such comorbidities in the Japanese chronic kidney disease population. Such comorbidities are a potential risk for poor physical activity, disability, falls, more frequent hospitalization and, especially, increased mortality. This study included a total of 23 stable outpatients, and measured several indices of muscle function, such as hand grip strength, isometric knee extension strength, Timed Up and Go test, and short physical performance battery. Relationships between these indices and kidney function, assessed by the estimated glomerular filtration rate, were then examined. Deterioration in muscle function and maintenance of posture were found to be associated with chronic kidney disease.