Association between screen time, including that for smartphones, and overweight/obesity among children in Japan: NICE EVIDENCE Study 4.

The association between screen time (ST), including that for smartphones, and overweight/obesity in children was examined separately for boys and girls, considering the influence of lifestyle factors. A cross-sectional study was conducted in 2,242 Japanese children (1,278 girls) aged 10-14 years. Overweight/obesity was defined by the International Obesity Task Force. Logistic regression analysis showed that only for girls, total ST (≥4 h), smartphone ST (≥3 h), and non-smartphone ST (≥2 h) were all independently and significantly associated with overweight/obesity compared to <2 h total ST, non-use of smartphones, and <1 h non-smartphone ST. Thus, smartphone ST ≥3 h and non-smartphone ST ≥2 h were additively associated with overweight/obesity in girls only. Girls having smartphone ST ≥3 h and non-smartphone ST ≥2 h were 6.79 times (95% CI: 3.11-14.81) more likely to have overweight/obesity than girls with less usage of both. In girls, when total ST was ≥4 < 5 h or smartphone ST was ≥2 h, the significant association with overweight/obesity disappeared when physical activity was ≥60 min/day and sleep time was ≥8.5 h. In addition, none of these associations was significant in boys. In Japanese girls, smartphone ST, non-smartphone ST, and total ST were all significantly associated with overweight/obesity. To avoid overweight/obesity, it is suggested to keep smartphone ST, non-smartphone ST, and total ST to <3 h, <2 h, and <4 h, respectively, and to engage in sufficient physical activity and sleep time.

Relationship between the magnitude of body mass index reductions and remission in patients with type 2 diabetes in real world settings: Analysis of nationwide patient registry in Japan (JDDM74).

AIMS: To determine the association between the magnitude of weight loss and incidence of remission according to baseline characteristics in patients with diabetes in clinical settings. METHODS: In total, 39 676 Japanese patients with type 2 diabetes aged ≥18 years with glycated haemoglobin (HbA1c) ≥6.5% and/or glucose-lowering drug prescription were identified from databases of specialists' clinics from 1989 and followed until September 2022. Remission was diagnosed as maintaining HbA1c <6.5% at least 3 months after cessation of a glucose-lowering drug. Factors associated with remission were evaluated by logistic regression analysis according to weight change in 1 year (i.e. ≥10%, 7.0-9.9%, 3.0-6.9% reduction, <3% change and ≥3.0% increase). RESULTS: During the study period, 3454 remissions occurred. The rates of remission were higher in the group with the greatest reduction of body mass index (BMI) in any category examined (i.e. baseline BMI, HbA1c, duration of diabetes and treatment). The incidences of remission per 1000 person-years were about 25 and 50, respectively, for those with BMI ≥22.5 and reductions in BMI of 7.0-9.9% and ≥10% in 1 year. Remissions per 1000 person-years were 99.2 and 91.8, respectively, for those with baseline HbA1c of 6.5-6.9 and a 10% BMI reduction and those not taking glucose-lowering drugs accompanied by a 10% BMI reduction. CONCLUSIONS: Modest weight losses of 3.0-7.9% were significantly associated with remission, but a minimum of 10% weight loss would be required in addition to an early diagnosis to achieve a 10% remission rate in clinical settings. Our results implied that remission may be expected with a relatively lower BMI in an Asian population compared with that was reported in Western populations if accompanied by weight loss.

Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73).

AIMS: To determine the incidence of remission and 1-year relapse from remission and associated factors in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 48 320 Japanese patients with type 2 diabetes aged ≥18 years, with glycated haemoglobin (HbA1c) levels ≥48 mmol/mol (6.5%) and/or glucose-lowering drug prescription, were identified from databases of specialist clinics from 1989 and followed until September 2022. Remission was defined as HbA1c <48 mmol/mol at least 3 months after cessation of a glucose-lowering drug. Relapse was defined as failure to maintain remission for 1 year. Factors associated with remission and relapse were evaluated by logistic regression analysis. RESULTS: The overall incidence of remissions per 1000 person-years was 10.5, and for those with HbA1c levels of 48 to 53 mmol/mol (6.5% to 6.9%), those taking no glucose-lowering drugs at baseline, and those with a ≥10% body mass index (BMI) reduction in 1 year, it was 27.8, 21.7 and 48.2, respectively. Shorter duration, lower baseline HbA1c, higher baseline BMI, higher BMI reduction at 1 year, and no glucose-lowering drugs at baseline were significantly associated with remission. Among 3677 persons with remission, approximately two-thirds (2490) relapsed within 1 year. Longer duration, lower BMI at baseline, and lower BMI reduction at 1 year were significantly associated with relapse. CONCLUSIONS: The results showed that the incidence of remission and predictors of relapse, especially baseline BMI, might differ greatly between East Asian and Western populations. Furthermore, the relationships of BMI reduction with remission and relapse may be greater in East Asian than in Western populations, implying ethnic differences in returning from overt hyperglycaemia to nearly normal glucose levels.

Fast walking and physical activity are independent contributors to improved physical function.

BACKGROUND AND OBJECTIVES: To clarify whether the presence or absence of fast walking and habitual physical activity are independently associated with the incidence of functional disability. METHODS: This historical cohort study was comprised of 9,652 (4,412 men, mean age 65 years) individuals aged 39-98 years without functional disability at baseline. Functional disability was determined based on the Japanese long-term care insurance system, which specified requirements for assistance in the activities of daily living. The impact of fast walking and habitual physical activity on the incidence of functional disability was analysed by Cox proportional hazards models. RESULTS: The follow-up period was a median of 3.7 years during which 165 patients were newly certified as having functional disability. In the multivariate analysis, baseline age in 5-year increments (hazard ratio 2.42 [95% confidence interval 2.18-2.69]), no habitual physical activity (1.56 [1.07-2.27]), and not fast walking (1.89 [1.32-2.69]) significantly increased the risk of functional disability after adjustment for covariates. The stratified analysis showed that compared with physical activity (+), the impact of physical activity (-) on the incidence of functional disability was observed in those aged ≥75 years regardless of fast walking (+). Fast walking (-) significantly increased the risk of disability compared with fast walking (+) in those aged <75 years regardless of a physical activity habit. CONCLUSION: In Japanese, slow walking speed and lack of a physical activity habit were shown to be independent risk factors for incident functional disability, with their impact differing according to age.

Associations among metabolic health, weight status, and various physical fitness components in Japanese adolescents: a cross-sectional study (NICE EVIDENCE study- Agano 3).

Aim was to examine associations among metabolic health, weight status, and various physical fitness (PF) components in 1744 Japanese adolescents aged 13-14. Anthropometric measurements and PF tests (20 m shuttle run test [20mSRT], handgrip strength/body mass [HG], standing long jump [SLJ], and sit ups [SU]) were administered. The bottom sex-specific quintile of PF indicated "low fit". Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to the International Obesity Task Force. Clustered metabolic risk was defined as the sum of Z scores for mean arterial pressure, non-high-density lipoprotein cholesterol, and HbA1c, divided by three, and ≥ 1 SD. Combination of weight status and scores for HG or SU were additively associated with clustered metabolic risk. Compared with the non-OW-moderate-high fit group, the OW-low HG group was 3.05 (95%CI: 1.88-4.97) times more likely to have clustered metabolic risk although risk was not significantly elevated in the OW-moderate-high HG group (1.52 [95%CI: 0.88-2.62]). A similar association was observed between OW and low SU scores but not between OW and low 20mSRT or SLJ scores. Adolescents with OW and moderate-high HG or SU scores had a lower prevalence of an unfavourable metabolic state than those with OW and low HG or SU results.

Utility of a Physical Fitness Score in Screening for Chronic Diseases.

We developed a new Physical Score (PS) consisting of comprehensive physical fitness indicators and elucidated the association between the resultant PS and metabolic diseases, i.e., diabetes, hypertension, dyslipidemia, fatty liver, and metabolic syndrome (MetS), among Japanese. Analyzed were 49,850 persons (30,039 men) aged 30 to 69 y who underwent physical fitness tests. Principal component analysis was performed on the correlation matrix of the physical fitness test results (relative grip strength, single-leg balance with eyes closed, and forward bending) according to sex and age. We defined the PS as the first principal component score. A formula was developed for various age groups comprised of men and women from 30 to 69 years of age from which the PS for each age and sex was calculated. The PS for both men and women was normally distributed with a value of 0 ± 1.15-1.16. Multivariate logistic regression analysis showed that the risk of metabolic diseases increased approximately 1.1-1.6 times per each 1-point reduction in the PS. The association between PS and MetS was particularly strong in that a 1-point reduction in the PS increased the risk of MetS by 1.54 times (95% confidence interval 1.46 to 1.62) in men and by 1.21 times (1.15 to 1.28) in women. The association between a lower PS and disease risk was stronger in younger men for fatty liver and in older men for MetS. Conversely, in women, the association between a lower PS and disease risk was stronger in older women for fatty liver and in younger women for MetS. For diabetes, hypertension, and dyslipidemia, the change in the impact of PS reductions across age groups was small. The PS is a useful and simple non-invasive tool for screening Japanese people for metabolic diseases.

Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease.

Sterol regulatory element-binding proteins (SREBPs) are master transcription factors for lipid synthesis, and SREBP-1 is important for fatty acid and triglyceride synthesis. SREBP-1 has two isoforms, SREBP-1a and SREBP-1c, which are splicing variants transcribed from the Srebf1 gene. Although SREBP-1a exhibits stronger transcriptional activity than SREBP-1c, hepatic SREBP-1c is considered more physiologically important. We generated SREBP-1a flox mice using the CRISPR/Cas9 system and hepatocyte- and macrophage-specific SREBP-1a knockout (KO) mice (LKO, liver-knockout; and mΦKO, macrophage-knockout). There were no significant differences among all the mouse genotypes upon feeding with a normal diet. However, feeding with a methionine- and choline-deficient (MCD) diet resulted in exacerbated liver injury in both KO mice. In LKO mice, fatty liver was unexpectedly exacerbated, leading to macrophage infiltration and inflammation. In contrast, in mΦKO mice, the fatty liver state was similar to that in flox mice, but the polarity of the macrophages in the liver was transformed into a proinflammatory M1 subtype, resulting in the exacerbation of inflammation. Taken together, we found that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in MCD diet-induced hepatitis.NEW & NOTEWORTHY Hepatocyte- and macrophage-specific SREBP-1a knockout mice were generated for the first time. This study reveals that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in methionine- and choline-deficient diet-induced hepatitis.

YAP1/TAZ activity maintains vascular integrity and organismal survival.

Radiation therapy is one of the major treatment modalities for patients with cancers. However, ionizing radiation (IR) damages not only cancer cells but also the surrounding vascular endothelial cells (ECs). Hippo pathway effector genes Yap1 and Taz are the two transcriptional coactivators that have crucial roles in tissue homeostasis and vascular integrity in various organs. However, their function in adult ECs at the steady state and after IR is poorly understood. Here, we report sex- and context-dependent roles of endothelial YAP1/TAZ in maintaining vascular integrity and organismal survival. EC-specific Yap1/Taz deletion compromised systemic vascular integrity, resulting in lethal circulation failure preferentially in male mice. Furthermore, EC-specific Yap1/Taz deletion induced acute lethality upon sublethal IR that was closely associated with exacerbated systemic vascular dysfunction and circulation failure. Consistent with these findings, RNA-seq analysis revealed downregulation of tight junction genes in Yap1/Taz-deleted ECs. Collectively, our findings highlight the importance of endothelial YAP1/TAZ for maintaining adult vascular function, which may provide clinical implications for preventing organ injury after radiation therapy.

Impact of metabolic syndrome and metabolic dysfunction-associated fatty liver disease on cardiovascular risk by the presence or absence of type 2 diabetes and according to sex.

BACKGROUND: To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex. METHODS: This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008 to 2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. The fatty liver index was used to determine the presence or absence of fatty liver that required a diagnosis of MAFLD. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model. RESULTS: During a median follow-up of 5.2 years, 2252 CAD and 3128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17-1.50)/1.41(1.28-1.57) for MAFLD only (without MetS), 1.78 (1.22-2.58)/1.66 (1.34-2.06) for MetS only (without MAFLD), and 2.10 (1.84-2.39)/1.73 (1.54-1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06-1.58), for MetS only 1.34 (0.84-2.13), and for MAFLD + MetS 1.22 (1.02-1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18-1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD. CONCLUSIONS: Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.

Starvation-induced transcription factor CREBH negatively governs body growth by controlling GH signaling.

cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.

Intensive oral care can reduce bloodstream infection with coagulase-negative staphylococci after neutrophil engraftment in allogeneic hematopoietic stem-cell transplantation.

PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.

Leisure-time physical activity and incidence of objectively assessed hearing loss: The Niigata Wellness Study.

Previous cohort study reported that high physical activity was associated with a low risk of self-reported hearing loss in women. However, no studies have examined the association between physical activity and the development of hearing loss as measured using an objective assessment of hearing loss in men and women. Here, we used cohort data to examine the association between leisure-time physical activity and incidence of objectively assessed hearing loss in men and women. Participants included 27 537 Japanese adults aged 20-80 years without hearing loss, who completed a self-administered physical activity questionnaire between April 2001 and March 2002. The participants were followed up for the development of hearing loss as measured by audiometry between April 2002 and March 2008. During follow-up, 3691 participants developed hearing loss. Compared with the none physical activity group, multivariable adjusted hazard ratios (HRs) for developing hearing loss were 0.93 (95% confidence interval (CI), 0.86-1.01) and 0.87 (0.81-0.95) for the medium (<525 MET-min/week) and high (≥525 MET-min/week) physical activity groups, respectively (p for trend = 0.001). The magnitude of risk reduction was slightly greater in vigorous-intensity activity than in moderate-intensity activity (p for interaction = 0.01). Analysis by sound frequency showed that the amount of physical activity was inversely associated with high frequency hearing loss development (p for trend <0.001), but not with low frequency hearing loss development (p for trend = 0.19). Higher level of leisure-time physical activity was associated with lower incidence of hearing loss, particularly for vigorous-intensity activities and high sound frequencies.

[Angioimmunoblastic T-cell lymphoma after immune checkpoint inhibitor-combined chemotherapy for lung cancer].

A 68-year-old male patient with lung adenocarcinoma, who was treated with chemotherapy and immune checkpoint inhibitors (ICIs), developed lymphadenopathy during treatment. His para-aortic lymph nodes increased to 2.0 cm in diameter. Both inguinal lymph nodes were 1.5 cm in diameter, and multiple hepatic masses appeared. After the ICI readministration, both inguinal lymph nodes increased to 2.0 cm in diameter, but the para-aortic lymph nodes and hepatic masses remained. Angioimmunoblastic T-cell lymphoma (AITL) diagnosis was established after the right inguinal lymph node biopsy, which was accompanied by an infiltration of Epstein-Barr virus (EBV)-encoded small ribonucleic acid-positive B-cells. After the ICI discontinuation, the inguinal lymph nodes decreased to 1.5 cm in diameter, but the para-aortic lymph nodes remained, and hepatic masses increased. Hepatic lesions were possibly lung cancer metastasis. The ICI administration and EBV reactivation were potentially associated with AITL development in the present case. The natural shrinkage of lymphoma after the ICI cessation implied the immunological mechanism like that of the methotrexate-related lymphoproliferative disease.

Hepatocyte ELOVL Fatty Acid Elongase 6 Determines Ceramide Acyl-Chain Length and Hepatic Insulin Sensitivity in Mice.

BACKGROUND AND AIMS: Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. We have previously shown that Elovl6 contributes to obesity-induced insulin resistance by modifying hepatic C16/C18-related FA composition. APPROACH AND RESULTS: To define the precise molecular mechanism by which hepatic Elovl6 affects energy homeostasis and metabolic disease, we generated liver-specific Elovl6 knockout (LKO) mice. Unexpectedly, LKO mice were not protected from high-fat diet-induced insulin resistance. Instead, LKO mice exhibited higher insulin sensitivity than controls when consuming a high-sucrose diet (HSD), which induces lipogenesis. Hepatic patatin-like phospholipase domain-containing protein 3 (Pnpla3) expression was down-regulated in LKO mice, and adenoviral Pnpla3 restoration reversed the enhancement in insulin sensitivity in HSD-fed LKO mice. Lipidomic analyses showed that the hepatic ceramide(d18:1/18:0) content was lower in LKO mice, which may explain the effect on insulin sensitivity. Ceramide(d18:1/18:0) enhances protein phosphatase 2A (PP2A) activity by interfering with the binding of PP2A to inhibitor 2 of PP2A, leading to Akt dephosphorylation. Its production involves the formation of an Elovl6-ceramide synthase 4 (CerS4) complex in the endoplasmic reticulum and a Pnpla3-CerS4 complex on lipid droplets. Consistent with this, liver-specific Elovl6 deletion in ob/ob mice reduced both hepatic ceramide(d18:1/18:0) and PP2A activity and ameliorated insulin resistance. CONCLUSIONS: Our study demonstrates the key role of hepatic Elovl6 in the regulation of the acyl-chain composition of ceramide and that C18:0-ceramide is a potent regulator of hepatic insulin signaling linked to Pnpla3-mediated NAFLD.

Impact of prior cerebrovascular disease and glucose status on incident cerebrovascular disease in Japanese.

BACKGROUND: Although both a history of cerebrovascular disease (CVD) and glucose abnormality are risk factors for CVD, few large studies have examined their association with subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose status, and their combinations on subsequent CVD using real-world data. METHODS: This is a retrospective cohort study including 363,627 men aged 18-72 years followed for ≥ 3 years between 2008 and 2016. Participants were classified as normoglycemia, borderline glycemia, or diabetes defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD (i.e. ischemic stroke, transient ischemic attack, and non-traumatic intracerebral hemorrhage) were identified according to claims using ICD-10 codes, medical procedures, and questionnaires. RESULTS: Participants' mean age was 46.1 ± 9.3, and median follow up was 5.2 (4.2, 6.7) years. Cox regression analysis showed that prior CVD + conferred excess risk for CVD regardless of glucose status (normoglycemia: hazard ratio (HR), 8.77; 95% CI 6.96-11.05; borderline glycemia: HR, 7.40, 95% CI 5.97-9.17; diabetes: HR, 5.73, 95% CI 4.52-7.25). Compared with normoglycemia, borderline glycemia did not influence risk of CVD, whereas diabetes affected subsequent CVD in those with CVD- (HR, 1.50, 95% CI 1.34-1.68). In CVD-/diabetes, age, current smoking, systolic blood pressure, high-density lipoprotein cholesterol, and HbA1c were associated with risk of CVD, but only systolic blood pressure was related to CVD risk in CVD + /diabetes. CONCLUSIONS: Prior CVD had a greater impact on the risk of CVD than glucose tolerance and glycemic control. In participants with diabetes and prior CVD, systolic blood pressure was a stronger risk factor than HbA1c. Individualized treatment strategies should consider glucose tolerance status and prior CVD.

Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the sodium-glucose cotransporter-2 inhibitor tofogliflozin.

Sodium-glucose cotransporter-2 inhibitors (SGLT2) are drugs that have been reported to have several effects through the regulation of plasma volume, for example, antihypertensive effects. This study aimed to clarify the impact of long-term administration and subsequent discontinuation of the SGLT2 inhibitor tofogliflozin on estimated plasma volume (ePV), brain natriuretic peptide (BNP) and the relationship between changes in ePV, BNP and body weight (BW). Data from 157 participants with type 2 diabetes receiving tofogliflozin monotherapy in a phase 3 study were analysed. Changes in variables or correlations among them during a 52-week administration and a 2-week post-treatment period were investigated. Percent change in ePV was calculated using the Strauss formula. Significant decreases in BW, ePV and ln-transformed BNP (ln-BNP) were noted by week 52. %ΔBW was not significantly correlated with %ΔePV and Δln-BNP, while %ΔePV was significantly correlated with Δln-BNP. Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased. %ΔBW was significantly correlated with %ΔePV and Δln-BNP. Furthermore, ePV and BNP were significantly higher than baseline levels.

A 52-week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study.

AIM: To compare the long-term efficacy of sodium-glucose co-transporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors as second-line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). MATERIALS AND METHODS: In a 52-week randomized open-label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. RESULTS: Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2 , 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C-peptide and high-density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). CONCLUSION: The HbA1c-lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.

Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure.

PURPOSE: This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). METHODS: Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). RESULTS: Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia"). CONCLUSIONS: Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

Accuracy of Japanese claims data in identifying diabetes-related complications.

PURPOSE: To evaluate the accuracy of various claims-based definitions of diabetes-related complications (coronary artery disease [CAD], heart failure, cerebrovascular disease and dialysis). METHODS: We evaluated data on 1379 inpatients who received care at the Niigata University Medical & Dental Hospital in September 2018. Manual electronic medical chart reviews were conducted for all patients with regard to diabetes-related complications and were used as the gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each claims-based definition associated with diabetes-related complications based on Diagnosis Procedure Combination (DPC), International Classification of Diseases, Tenth Revision (ICD-10) codes, procedure codes and medication codes were calculated. RESULTS: DPC-based definitions had higher sensitivity, specificity, and PPV than ICD-10 code definitions for CAD and cerebrovascular disease, with sensitivity of 0.963-1.000 and 0.905-0.952, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. Sensitivity, specificity, and PPV were high using procedure codes for CAD and dialysis, with sensitivity of 0.963 and 1.000, specificity of 1.000 and 1.000, and PPV of 1.000 and 1.000, respectively. DPC and/or ICD-10 codes + medication were better for heart failure than the ICD-10 code definition, with sensitivity of 0.933, specificity of 1.000, and PPV of 1.000. The PPVs were lower than 60% for all diabetes-related complications using ICD-10 codes only. CONCLUSION: The DPC-based definitions for CAD and cerebrovascular disease, procedure codes for CAD and dialysis, and DPC or ICD-10 codes with medication codes for heart failure could accurately identify these diabetes-related complications from claims databases.

Physical Fitness and Dyslipidemia Among Japanese: A Cohort Study From the Niigata Wellness Study.

BACKGROUND: Grip strength reflects systemic muscle strength and mass and is reportedly associated with various metabolic variables. However, its prognostic association with dyslipidemia is unknown. We examined the association of grip strength and other physical fitness markers with the incidence of dyslipidemia among Japanese adults. METHODS: A total of 16,149 Japanese (6,208 women) individuals aged 20-92 years who underwent a physical fitness test between April 2001 and March 2002 were included in this cohort study. Grip strength, vertical jump, single-leg balance with eyes closed, forward bending, and whole-body reaction time were evaluated at baseline. Dyslipidemia was annually determined based on fasting serum lipid profiles and self-reported dyslipidemia from April 2001 to March 2008. RESULTS: During the follow-up period, 4,458 (44.9%) men and 2,461 (39.6%) women developed dyslipidemia. A higher relative grip strength (grip strength/body mass index) was associated with a lower incidence of dyslipidemia among both men and women (P for trend <0.001). Compared with those for the first septile, the hazards ratios and 95% confidence intervals (CIs) for the seventh septile were 0.56 (95% CI, 0.50-0.63) for men and 0.69 (95% CI, 0.58-0.81) for women. Moreover, relative vertical jump (vertical jump strength/body mass index) was also inversely associated with the incidence of dyslipidemia among both men and women (P for trend <0.001). There was no association between other physical fitness and dyslipidemia among both men and women. CONCLUSION: Relative grip strength and vertical jump may be useful risk markers of the incidence of dyslipidemia.