研究者詳細 - 佐藤　達也

論文 - 佐藤　達也

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Response to exercise-induced blood pressure elevation is blunted in wrist-cuff automated oscillometric measurement in healthy young college students.

Tatsuya Sato, Nobutoshi Ichise, Yoshinori Terashima, Aoi Kato, Hiroya Yamazaki, Shunsuke Jimbo, Noritsugu Tohse

Physiological reports 8 ( 17 ) e14570 2020年09月 [査読有り] [国際誌]

担当区分：筆頭著者 , 責任著者

BACKGROUND: A wrist-cuff automated oscillometric device is portable and useful for self-monitoring of blood pressure (BP) at home and outdoors when an upper arm device is not available. Although the height of the forearm in wrist BP measurement is acknowledged to be the major cause of measurement error, it remains unclear whether exercise affects subsequent wrist BP measurement. METHODS AND RESULTS: Ninety-seven healthy college students (median age of 20 years with an age range of 19 to 36 years, 70.1% males) participated in this study. Care was taken to keep the position of the wrist at a level near the upper arm level in BP measurement. At rest, BP measured by a wrist-cuff oscillometric device (Omron HEM-6183) was generally acceptable when it was compared with BP measured by an upper arm oscillometric device (Omron HEM-7130-HP) and with BP measured by the auscultatory method using a mercury sphygmomanometer. However, the ratio of systolic BP measured by oscillometric devices just after a two-step exercise test to that before exercise on the wrist (1.22 ± 0.14) was significantly lower than the ratio on the upper arm (1.27 ± 0.14), and the difference was significantly correlated with exercise-induced increase in pulse rate (Spearman's ρ = 0.23), suggesting a possible role of autonomic nerve activity in the blunted response to exercise-induced BP elevation in wrist BP measurement. CONCLUSIONS: The results indicate that the blunted response to exercise-induced BP elevation should be considered in wrist BP measurement when using a wrist-cuff oscillometric device.

Reply to the comment of Hirota et al. on "Accuracy of flash glucose monitoring in insulin-treated patients with type 2 diabetes".

Tatsuya Sato, Hiroto Oshima, Kei Nakata, Yukishige Kimura, Toshiyuki Yano, Masato Furuhashi, Masaya Tannno, Takayuki Miki, Tetsuji Miura

Journal of diabetes investigation 11 ( 1 ) 256 - 256 2020年01月 [査読有り] [国内誌]

担当区分：筆頭著者

Longitudinal impact of dapagliflozin treatment on ventricular repolarization heterogeneity in patients with type 2 diabetes.

Tatsuya Sato, Takayuki Miki, Shinya Furukawa, Bunzo Matsuura, Yoichi Hiasa, Hirofumi Ohnishi, Masaya Tanno, Tetsuji Miura

Journal of diabetes investigation 10 ( 6 ) 1593 - 1594 2019年11月 [査読有り] [国内誌]

担当区分：筆頭著者

Accuracy of flash glucose monitoring in insulin-treated patients with type 2 diabetes.

Tatsuya Sato, Hiroto Oshima, Kei Nakata, Yukishige Kimura, Toshiyuki Yano, Masato Furuhashi, Masaya Tanno, Takayuki Miki, Tetsuji Miura

Journal of diabetes investigation 10 ( 3 ) 846 - 850 2019年05月 [査読有り] [国内誌]

担当区分：筆頭著者

The present study evaluated the accuracy of interstitial glucose measurements by flash glucose monitoring (FGM) and continuous glucose monitoring (CGM). Five diabetes patients simultaneously underwent FGM (FreeStyle Libre Pro) and CGM (iPro™2), and their glucose levels were compared with venous blood and capillary blood glucose levels. The range of daily venous blood glucose levels (30 measurements) was 70-245 mg/dL, with a median of 138 mg/dL. There were good correlations of glucose levels measured by FGM (r2 = 0.90, mean absolute relative difference 8.2 ± 5.6%), CGM (r2 = 0.86, mean absolute relative difference 9.2 ± 9.1%) and capillary blood (r2 = 0.87, mean absolute relative difference 7.2 ± 7.2%) with venous blood glucose levels. The accuracy of FGM measurements was also shown against CGM, with 99.9% of the FGM values (1,279 measurements) being within the Parkes error grid zones A and B. The results suggest that the accuracy of FGM is similar to that of CGM, and that FGM is a useful tool for determining daily glucose profile.

mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function.

Tatsuya Sato, Hsiang-Chun Chang, Marina Bayeva, Jason S Shapiro, Lucia Ramos-Alonso, Hidemichi Kouzu, Xinghang Jiang, Ting Liu, Sumeyye Yar, Konrad T Sawicki, Chunlei Chen, María Teresa Martínez-Pastor, Deborah J Stumpo, Paul T Schumacker, Perry J Blackshear, Issam Ben-Sahra, Sergi Puig, Hossein Ardehali

Proceedings of the National Academy of Sciences of the United States of America 115 ( 27 ) E6291-E6300 2018年07月 [査読有り] [国際誌]

担当区分：筆頭著者

Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp display cardiac dysfunction with iron deficiency, demonstrating that TTP is necessary for maintaining cardiac function in the setting of low cellular iron. Altogether, our results describe a pathway that is activated in iron deficiency to regulate mitochondrial function to match the availability of Fe/S clusters.

Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes.

Tatsuya Sato, Takayuki Miki, Hirofumi Ohnishi, Tomohisa Yamashita, Akifumi Takada, Toshiyuki Yano, Masaya Tanno, Akihito Tsuchida, Tetsuji Miura

Diabetic medicine : a journal of the British Diabetic Association 34 ( 10 ) 1367 - 1371 2017年10月 [査読有り] [国際誌]

担当区分：筆頭著者

AIMS: To test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. METHODS: We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. RESULTS: Sodium-glucose co-transporter-2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319; P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. CONCLUSIONS: The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2.

Tatsuya Sato, Takeshi Kobayashi, Atsushi Kuno, Takayuki Miki, Masaya Tanno, Hidemichi Kouzu, Takahito Itoh, Satoko Ishikawa, Takashi Kojima, Tetsuji Miura, Noritsugu Tohse

American journal of physiology. Heart and circulatory physiology 306 ( 7 ) H1054-65 2014年04月 [査読有り] [国際誌]

担当区分：筆頭著者 , 責任著者

In the present study, we examined if and how cardiac ion channels are modified by type 2 diabetes mellitus (T2DM). Subendocardial (Endo) myocytes and subepicardial (Epi) myocytes were isolated from left ventricles of Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) rats, a rat model of T2DM, and Otsuka-Long-Evans-Tokushima (LETO) rats (nondiabetic control rats). Endo and Epi myocytes were used for whole cell patch-clamp recordings and for protein and mRNA analyses. Action potential durations in Endo and Epi myocytes were longer in OLETF rats than in LETO rats, and the difference was larger in Endo myocytes. Steady-state transient outward K+ current (Ito) density was reduced in Endo but not Epi myocytes of OLETF rats compared with LETO rats, although the contribution of the fast component of Ito recovery from inactivation was smaller in both Endo and Epi myocytes of OLETF rats than in LETO rats. Kv4.2 protein was reduced only in Endo myocytes in OLETF rats, although voltage-gated K+ channel-interacting protein 2 (KChIP2) protein levels in both Endo and Epi myocytes were lower in OLETF rats than in LETO rats. Corresponding regional differences in mRNA levels of KChIP2 and Kv4.2 were observed between OLETF and LETO rats. mRNA levels of Iroquois homeobox 5 in Endo myocytes were 53% higher in OLETF rats than in LETO rats. Densities of inward rectifier K+ current and L-type Ca2+ current and mRNA levels of Kv4.3 and Kv1.4 were similar in OLETF and LETO rats. In conclusion, T2DM induces Endo-predominant prolongation of the action potential duration via a reduction of the fast component of Ito recovery from inactivation and reduced steady-state Ito, in which downregulation of Kv4.2 and KChIP2 may be involved. Increased Iroquois homeobox 5 expression may underlie Kv4.2 downregulation in T2DM.

Histopathology of the pancreas in fulminant type 1 diabetes after 23-year follow-up: a case report.

Tatsuya Sato, Takayuki Miki, Naoto Murakami, Yoshihiko Hirohashi, Hidemichi Kouzu, Masato Furuhashi, Masaya Tanno, Satoshi Yuda, Shigeyuki Saitoh, Tadashi Hasegawa, Tetsuji Miura

Pathology international 62 ( 12 ) 827 - 9 2012年12月 [査読有り] [国際誌]

担当区分：筆頭著者

Roles of phospho-GSK-3β in myocardial protection afforded by activation of the mitochondrial K ATP channel.

Yoshiaki Terashima, Tatsuya Sato, Toshiyuki Yano, Ole Maas, Takahito Itoh, Takayuki Miki, Masaya Tanno, Atsushi Kuno, Kazuaki Shimamoto, Tetsuji Miura

Journal of molecular and cellular cardiology 49 ( 5 ) 762 - 70 2010年11月 [査読有り] [国際誌]

担当区分：筆頭著者

The aim of this study was to determine the roles of glycogen synthase kinase-3β (GSK-3β) in cardioprotection by activation of the mitochondrial ATP-sensitive K(+) channel (mK(ATP) channel). In isolated rat hearts, an mK(ATP) activator, diazoxide, and a GSK-3β inhibitor, SB216763, similarly limited infarct size and the combination of these agents did not afford further protection. The protection by pre-ischemic treatment with diazoxide was abolished by inhibition of protein kinase C-ε (PKC-ε) or phosphatidylinositol-3-kinase (PI3K) upon reperfusion. Infusion of a GSK-3β inhibitor (LiCl), but not diazoxide, during reperfusion limited infarct size. Inhibition of PKC-ε or PI3K did not affect the protection by LiCl. Diazoxide infusion alone did not induce GSK-3β phosphorylation. However, diazoxide infusion before ischemia increased mitochondrial phospho-GSK-3β level and reduced cyclophilin-D (CypD) binding to adenine nucleotide translocase (ANT) at 10 min after reperfusion. This diazoxide-induced GSK-3β phosphorylation was inhibited by blockade of the mK(ATP) channel before ischemia and by blockade of PKC-ε, PI3K or the adenosine A2b receptor at the time of reperfusion. Inhibition of GSK-3β by LiCl during reperfusion increased phospho-GSK-3β but had no significant effect on CypD-ANT binding. These results suggest that GSK-3β phosphorylation at the time of reperfusion by a PKC-ε, PI3K- and A2b receptor-dependent mechanism contributes to prevention of myocardial necrosis by pre-ischemic activation of the mK(ATP) channel. Inhibition of CypD-ANT interaction may contribute to mK(ATP)-induced myocardial protection, though it is not the sole mechanism of phospho-GSK-3β-mediated cytoprotection.

Incorporation of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Health Stage of Cardiovascular-Kidney-Metabolic Syndrome Improves Predictive Ability for Coronary Artery Disease in a Japanese General Population.

Wataru Kawaharata, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Itaru Hosaka, Hiroki Aida, Rie Matsumori, Kei Nakata, Keitaro Nishizawa, Toru Suzuki, Hidemichi Kouzu, Nagisa Hanawa, Masato Furuhashi

Journal of the American Heart Association e043173 2025年08月 [査読有り] [国際誌]

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a recently proposed condition encompassing metabolic dysfunction, chronic kidney disease, and cardiovascular diseases including coronary artery disease (CAD). Although concomitant metabolic dysfunction-associated steatotic liver disease (MASLD) exacerbates CKM syndrome, MASLD is not included in the original stratification (stages 0-3) for predicting cardiovascular disease (stage 4). METHODS: We investigated whether the addition of MASLD in the original health stage of CKM syndrome improves the risk stratification of CAD in Japanese participants who underwent annual health checkups. A total of 18 358 participants were categorized by the original health stages (stages 0-3) or modified health stages incorporating MASLD without chronic kidney disease in stage 2 and MASLD with chronic kidney disease in stage 3 to analyze the predictive ability for CAD during a 10-year period. RESULTS: Kaplan-Meier survival curve analysis showed that the modified classification more effectively stratified the risk of CAD than did the original CKM health stage. In Cox hazard proportional analyses after adjustment of confounders, hazard ratios in the original and modified stages 2/3 were 1.63 (95% CI, 1.27-2.11; P<0.001), 2.41 (95% CI, 0.34-17.4; P=0.381), 1.58 (95% CI, 1.23-2.05; P<0.001), and 2.56 (95% CI, 1.66-3.95; P<0.001), respectively. Risk discrimination significantly improved in the modified classification evaluated by integrated discrimination improvement. Furthermore, machine learning-mediated feature importance analyses using random forest and extreme gradient boosting identified MASLD as a key predictor of CAD with a high value of the Shapley Additive Explanations, indicating strong contribution in models. CONCLUSIONS: The modified health stage classification of CKM syndrome incorporating MASLD improves the accuracy of predicting new onset of CAD in a Japanese general population.

Association of Difference Between eGFR From Cystatin C and Creatinine and Serum GDF-15 With Adverse Outcomes in Diabetes Mellitus.

Tomohito Gohda, Nozomu Kamei, Marenao Tanaka, Masato Furuhashi, Tatsuya Sato, Mitsunobu Kubota, Michiyoshi Sanuki, Takeo Koshida, Shinji Hagiwara, Yusuke Suzuki, Maki Murakoshi

Journal of cachexia, sarcopenia and muscle 16 ( 4 ) e70011 2025年08月 [査読有り] [国際誌]

BACKGROUND: Protein catabolism and chronic inflammation drive sarcopenia and frailty in individuals with diabetes mellitus and chronic kidney disease (CKD). The difference between estimated glomerular filtration rates derived from cystatin C and creatinine (eGFRcys and eGFRcr, respectively), termed eGFRdiff, along with growth differentiation factor-15 (GDF-15) levels, have emerged as markers of metabolic and inflammatory dysregulation. Lower eGFRdiff and elevated GDF-15 levels are associated with sarcopenia, frailty, CKD progression and mortality. However, their interplay and respective impacts on CKD progression and mortality remain unclear. METHODS: A total of 638 Japanese individuals with diabetes mellitus were stratified into tertiles based on eGFRdiff. Serum GDF-15 levels were measured using enzyme-linked immunosorbent assays. The relationships between eGFRdiff and GDF-15 were assessed using Spearman's correlation coefficients. Multivariate ordered logistic regression was used to evaluate the association between eGFRdiff and GDF-15 tertiles, with GDF-15 as the dependent variable and eGFRdiff as the independent variable, adjusting for covariates including age, sex, urinary albumin-to-creatinine ratio (UACR) and eGFRcr or eGFRcys. Cox proportional hazards models with restricted cubic splines were used to examine associations between eGFRdiff and GDF-15 (independent variables) with CKD progression (≥ 30% decline in eGFRcr from baseline) and mortality (dependent variables). These models were adjusted for age, sex, glycated haemoglobin, UACR and eGFRcr. RESULTS: The median age was 65 years (interquartile range: 58-73), and 53.9% of participants were male. Over median follow-up periods of 5.3 years for CKD progression and 5.4 years for mortality, 75 participants (11.8%) experienced CKD progression and 44 (6.9%) died. GDF-15 levels inversely correlated with eGFRdiff (r = -0.35, p < 0.001). Higher eGFRdiff values were associated with lower odds of being in a higher GDF-15 tertile (odds ratio 0.86; 95% confidence interval [CI]: 0.76-0.97; p = 0.01). Both lower eGFRdiff and higher GDF-15 levels were independently associated with adverse outcomes: CKD progression (GDF-15, hazard ratio [HR] 1.36, 95% CI: 1.02-1.81, p < 0.05; eGFRdiff, HR 0.67, 95% CI: 0.58-0.78, p < 0.0001) and mortality (GDF-15, HR 2.35, 95% CI: 1.63-3.41, p < 0.0001; eGFRdiff: 0.80, 95% CI: 0.65-0.99, p < 0.05). CONCLUSIONS: Both eGFRdiff and GDF-15 were independently associated with adverse outcomes in individuals with diabetes mellitus. GDF-15 showed a stronger association with mortality, whereas eGFRdiff was more strongly linked to CKD progression. These findings underscore the potential utility of these markers in risk stratification for diabetes-related complications and may guide individualized interventions in clinical practice.

Plasma hepcidin level is elevated by water immersion‐induced central fatigue via hepatic inflammatory response in male and female rats

Takuro Karaushi, Toshifumi Ogawa, Hiroyori Fusagawa, Taiki Kudo, Yuito Inoue, Takashi Yamada, Nobutoshi Ichise, Tatsuya Sato, Noritsugu Tohse

Physiological Reports 13 ( e70468 ) 2025年08月 [査読有り]

担当区分：責任著者

The health stage of cardiovascular-kidney-metabolic (CKM) syndrome is useful for predicting all-cause mortality in patients with type 2 diabetes: a cohort study in a period prior to the standard use of recent pharmacotherapy.

Keitaro Nishizawa, Marenao Tanaka, Tatsuya Sato, Tomohito Gohda, Nozomu Kamei, Maki Murakoshi, Yukinori Akiyama, Wataru Kawaharata, Hiroki Aida, Hidemichi Kouzu, Naoya Yama, Mitsunobu Kubota, Michiyoshi Sanuki, Yusuke Suzuki, Masato Furuhashi

Journal of diabetes and its complications 39 ( 10 ) 109146 - 109146 2025年07月 [査読有り] [国際誌]

AIM: Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined systemic condition linking cardiovascular disease, chronic kidney disease and metabolic disorders including type 2 diabetes (T2D). Although the CKM staging has been proposed for integrated risk assessment, its association with all-cause mortality in patients with T2D remains unclear. We investigated the prognosis in patients with T2D assigned by the CKM health stage. METHODS: A total of 632 Japanese patients with T2D were enrolled. The primary endpoint was all-cause death. RESULTS: The numbers of the recruited patients with stages 2, 3 and 4 were 353 (55.9 %), 116 (18.3 %) and 163 (25.8 %), respectively. During a median follow-up of 64 months (35,327 person-months), 62 patients (9.8 %) died. Kaplan-Meier survival curves analysis showed significant differences in cumulative mortality among CKM health stages (log-rank test: P < 0.001) with higher cumulative mortality in stages 3 and 4 than in stage 2. Multivariable Cox proportional hazard models after adjustment of age, sex, body mass index, current smoking habit, cancer, relevant medications and hemoglobin A1c showed that adjusted hazard ratios (HRs) [95 % confidence intervals] for all-cause death were significantly higher in patients with stages 3 (2.25[1.08-4.69]) and those with stage 4 (2.87[1.41-5.84]) than in those with stage 2 as the reference. After additional adjustment of N-terminal pro-brain natriuretic peptide and estimated glomerular filtration rate among definition criteria for staging, the association of stages with all-cause death remained statistically significant in only stage 4 (2.16[1.02-4.56]). CONCLUSION: The CKM health staging is useful for predicting all-cause mortality in Japanese patients with T2D.

Association among circulating erythropoietin-producing hepatoma A2, progranulin, and kidney function in individuals with diabetes.

Maki Murakoshi, Nozomu Kamei, Kenichiro Abe, Takumi Iwasawa, Kazunori Kato, Marenao Tanaka, Tatsuya Sato, Masato Furuhashi, Mitsunobu Kubota, Michiyoshi Sanuki, Yusuke Suzuki, Tomohito Gohda

Journal of diabetes investigation 2025年07月 [査読有り] [国内誌]

BACKGROUND: Erythropoietin-producing hepatoma A2 (EphA2), a receptor for progranulin (PGRN), which is a growth factor associated with metabolic disorders, is implicated in inflammation and atherosclerotic diseases. Since both EphA2 and PGRN play roles in diabetic kidney disease (DKD) and cardiovascular disease (CVD), this study examined their association with renal function and CVD markers in individuals with diabetes. In addition, the diagnostic value of EphA2 and PGRN in predicting renal impairment was evaluated. METHODS: Circulating EphA2 and PGRN levels were measured using enzyme-linked immunosorbent assay in 735 participants with diabetes. Clinical data, including biometric parameters, physiological measurements, and comorbidities, were collected for analysis. RESULTS: Both EphA2 and PGRN levels positively correlated with older age, elevated blood pressure, higher urinary albumin-to-creatinine ratio (UACR), and brain natriuretic peptide (BNP) levels but negatively correlated with estimated glomerular filtration rate (eGFR). Multivariate logistic regression analysis revealed that EphA2 was an independent predictor of eGFR <60 mL/min/1.73 m2, even after adjusting for UACR and CVD risk factors and glycated hemoglobin. Although PGRN was also independently associated with eGFR <60 mL/min/1.73 m2, its association was weaker than that of EphA2. Conversely, when UACR ≥30 mg/g was used as the dependent variable, PGRN emerged as a stronger independent determinant than EphA2, even after adjusting for eGFR and CVD risk factors. CONCLUSIONS: EphA2 and PGRN levels are significantly associated with renal function in individuals with diabetes. These findings suggest that EphA2 and PGRN could serve as novel biomarkers for kidney impairment, independent of established CVD markers in this population.

Treatment with pemafibrate ameliorates fatty liver index and atherogenic lipid profiles in Japanese patients with type 2 diabetes mellitus.

Toru Suzuki, Tatsuya Sato, Marenao Tanaka, Kei Nakata, Keisuke Endo, Hiroki Aida, Wataru Kawaharata, Itaru Hosaka, Araya Umetsu, Toshifumi Ogawa, Yukinori Akiyama, Masato Furuhashi

Frontiers in endocrinology 16 1496671 - 1496671 2025年07月 [査読有り] [国際誌]

担当区分：筆頭著者

BACKGROUND: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, ameliorates hypertriglyceridemia. We investigated the effects of pemafibrate on steatotic liver disease (SLD) in relation to various atherogenic lipid profiles. METHODS: Thirty-nine Japanese patients with both type 2 diabetes mellitus (T2DM) and hypertriglyceridemia (men/women: 24/15, mean age: 58.2 years, median duration of diabetes: 5.0 years) were treated with 0.2 mg/day of pemafibrate for 12 months (M). SLD was estimated by fatty liver index (FLI), which is calculated by using waist circumference, body mass index and levels of triglycerides and γ-glutamyl transpeptidase. RESULTS: Treatment with pemafibrate significantly increased mean levels of high-density lipoprotein cholesterol (HDL-C) (baseline/3M/6M/12M: 46/55/55/54 mg/dL) and decreased median levels of triglycerides (baseline/3M/6M/12M: 211/112/99/98 mg/dL), non-HDL-C (146/128/125/121 mg/dL), small dense low-density lipoprotein cholesterol (45/33/30/30 mg/dL) and remnant-like particle cholesterol (8.1/2.6/2.3/2.4 mg/dL). There was no significant change in hemoglobin A1c level over time. FLI (mean ± standard deviation: 68.1 ± 21.9 vs. 39.6 ± 25.0, P < 0.001), but not FIB-4 index as a marker of hepatic fibrosis (median [interquartile range]: 1.04 [0.78-1.39] vs. 1.01 [0.68-1.36], P = 0.909), was significantly decreased by treatment with pemafibrate for 12M, and the proportion of patients with metabolic dysfunction-associated SLD (MASLD) was significantly decreased from 92.3% (baseline) to 61.5% (12M). CONCLUSIONS: Pemafibrate ameliorates MASLD estimated by FLI in addition to various atherogenic lipid profiles in Japanese hypertriglyceridemia patients with T2DM in the past mean 5 years. An early intervention with pemafibrate might contribute to prevention of the development of MASLD and atherosclerotic cardiovascular disease.

Association of the Glycated Albumin-to-Glycated Haemoglobin Ratio With Mortality in Type 2 Diabetes: A Retrospective Cohort Analysis.

Tomohito Gohda, Nozomu Kamei, Marenao Tanaka, Masato Furuhashi, Tatsuya Sato, Mitsunobu Kubota, Michiyoshi Sanuki, Risako Mikami, Koji Mizutani, Yusuke Suzuki, Maki Murakoshi

Endocrinology, diabetes & metabolism 8 ( 4 ) e70072 2025年07月 [査読有り] [国際誌]

INTRODUCTION: The glycated albumin-to-glycated haemoglobin (GA/HbA1c) ratio is a potential marker of glycaemic variability; however, its association with adverse clinical outcomes in type 2 diabetes remains unclear. We aimed to determine whether the GA/HbA1c ratio is a better predictor of mortality and chronic kidney disease (CKD) progression than GA alone in type 2 diabetes. METHODS: This retrospective cohort analysis included 571 Japanese participants with type 2 diabetes who were stratified into tertiles based on their GA/HbA1c ratio. Cox proportional hazards models assessed associations between the GA/HbA1c ratio and mortality or CKD progression (≥ 30% decline in the estimated glomerular filtration rate [eGFR]), adjusting for age, sex, urinary albumin-to-creatinine ratio, eGFR, body mass index, haemoglobin and serum albumin. RESULTS: In this cohort, the median age was 67 years, and 53.9% were male. During the median follow-up of 5.4 and 5.3 years for mortality and CKD progression, respectively, 40 (7.0%) participants died and 70 (12.3%) experienced CKD progression. For mortality, the GA/HbA1c ratio demonstrated a U-shaped association: although both the lowest (T1) and highest (T3) tertiles showed higher mortality risks than the middle tertile (T2), this association was significant for only T3 (hazard ratio, 1.46; 95% CI, 1.05-2.04). Neither GA nor HbA1c alone was significantly associated with mortality. For CKD progression, GA alone showed a U-shaped association, with both T1 and T3 exhibiting non-significantly higher risks than T2. Neither the GA/HbA1c ratio nor HbA1c alone was associated with CKD progression. CONCLUSIONS: In individuals with type 2 diabetes, a higher GA/HbA1c ratio was associated with an increased risk of mortality but not with CKD progression. However, given the retrospective design and limited sample size, these findings should be interpreted with caution and confirmed in larger, prospective studies.

Mapping research trends in obsessive-compulsive disorder before and after the COVID-19 pandemic: a bibliometric analysis focusing on its molecular mechanisms.

Yuito Inoue, Nobutoshi Ichise, Wataru Ukai, Jun Shinozaki, Toshifumi Ogawa, Takuro Karaushi, Marenao Tanaka, Yukinori Akiyama, Masato Furuhashi, Atsushi Kuno, Tatsuya Sato

Frontiers in psychiatry 16 1615497 - 1615497 2025年07月 [査読有り] [国際誌]

担当区分：責任著者

Obsessive-compulsive disorder (OCD) is a psychiatric disorder that primarily develops during adolescence, and is characterized by obsessive thoughts and compulsive behaviors. Although multiple factors including heredity, environment, and abnormalities in neural networks and synapses are involved in the onset and exacerbation of OCD, their underlying molecular mechanisms have not been fully elucidated. In addition, recent studies have demonstrated that the novel coronavirus disease (COVID-19) pandemic worsened OCD phenotypes. Hence, this global crisis may have changed the field of molecular-focused OCD research. We conducted a brief bibliometric analysis to investigate changes in prevalent topics in molecular-focused OCD research before (2015-2019) and after (2020-2025) the COVID-19 pandemic using Web of Science and VOSviewer. "Schizophrenia" and "metaanalysis" remained highly ranked terms in molecular-focused OCD research. In terms of neurotransmitters, the term "serotonin" became more prevalent than "dopamine" after the COVID-19 pandemic. In addition, research interest shifted toward younger populations, and there was a noticeable increase in terms related to neural networks such as "connectivity". However, only a few specific molecular mechanisms or cellular physiological pathways by which COVID-19 exacerbates OCD have been identified. To address this gap, an additional post hoc analysis focusing on inflammation-related terms was conducted, revealing the emergence of "oxidative stress" and "c-reactive protein" in studies published after the COVID-19 pandemic. The findings of this study highlight several potential clues for elucidating the pathophysiology of OCD and identifying aggravating factors such as COVID-19, while also emphasizing the importance of continued molecular-focused research to establish novel therapeutic targets.

Small Dense Low-Density Lipoprotein Cholesterol and Renal Function: A Missing Link in Cardiovascular Risk Assessment for Chronic Kidney Disease Patients - Reply.

Marenao Tanaka, Tatsuya Sato, Wataru Kawaharata, Hiroki Aida, Masato Furuhashi

Circulation journal : official journal of the Japanese Circulation Society 89 ( 6 ) 848 - 849 2025年05月 [査読有り] [国内誌]

Fatty Acid Metabolism Regulators Have Pivotal Roles in the Pathogenesis of Ovarian Carcinoma

Megumi Watanabe, Motoki Matsuura, Tatsuya Sato, Makoto Usami, Tsuyoshi Saito, Masato Furuhashi, Kohichi Takada, Hiroshi Ohguro

International Journal of Molecular Sciences 2025年05月 [査読有り]

The serum γ-Glutamyltransferase Level is Associated with the Development of Hypertension in Alcohol Infrequent Drinkers but not in Frequent Drinkers.

Kazuma Mori, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Internal medicine (Tokyo, Japan) ( Japanese Society of Internal Medicine ) 2025年04月 [査読有り] [国内誌]

Background The controversy persists regarding whether the serum level of γ-glutamyltransferase (GGT), a marker of liver damage, is associated with hypertension irrespective of alcohol intake. Methods We investigated the relationship between the GGT level and new-onset hypertension during a 10-year follow-up period in Japanese individuals who underwent annual health examinations (n=28,990). After excluding subjects without systolic blood pressure and GGT data and those with hypertension at baseline, a total of 18,618 subjects (men/women: 11,262/7,356, mean age: 44 years) were enrolled. Results During the follow-up period, 2,753 men (24.4%) and 837 women (11.4%) developed hypertension. When the subjects were divided by quartiles of GGT at baseline (Q1-Q4), multivariable Cox proportional hazard model analyses after adjustment for age, sex, systolic blood pressure, body mass index, levels of uric acid, estimated glomerular filtration rate, family history of hypertension, habits of current smoking and alcohol drinking, and diagnosis of diabetes mellitus and dyslipidemia showed that hazard risks (HRs) for the development of hypertension were significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group. A significant interaction was observed between alcohol drinking habits and the GGT level at baseline for the development of hypertension (p=0.022), and adjusted HRs were similarly significant in alcohol infrequent drinkers (≤5 days/week). However, the GGT level was not significantly associated with the development of hypertension in frequent alcohol drinkers (≥6 days/week). Conclusions A high GGT level is an independent predictor of new-onset hypertension in infrequent alcohol drinkers but not in frequent drinkers.

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