論文 - 古橋　眞人

日本人におけるFLIによるNAFLDの予測

高橋 聖子, 田中 希尚, 東浦 幸村, 塙 なぎさ, 大西 浩文, 古橋 眞人

日本内科学会雑誌 ( (一社)日本内科学会 )  111 ( Suppl. ) 198 - 198  2022年02月

日本人におけるFLIによるNAFLDの予測

高橋 聖子, 田中 希尚, 東浦 幸村, 塙 なぎさ, 大西 浩文, 古橋 眞人

日本内科学会雑誌 ( (一社)日本内科学会 )  111 ( Suppl. ) 198 - 198  2022年02月

A case of membranous nephropathy secondary to asymptomatic Graves’ disease

Norihito Moniwa, Yu Shioya, Yufu Gocho, Satoko Takahashi, Marenao Tanaka, Masato Furuhashi, Setsuko Kuroda, Taketsugu Hama, Yuko Shima, Yayoi Ogawa, Tetsuji Miura

CEN Case Reports ( Springer Science and Business Media LLC )   2022年01月

DOI

Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy.

Masato Furuhashi, Ichiro Sakuma, Takeshi Morimoto, Yukimura Higashiura, Akiko Sakai, Megumi Matsumoto, Mio Sakuma, Michio Shimabukuro, Takashi Nomiyama, Osamu Arasaki, Koichi Node, Shinichiro Ueda

Journal of atherosclerosis and thrombosis   29 ( 1 ) 24 - 37  2022年01月  [国内誌]

　概要を見る

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial. METHODS: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin (n=122) or sitagliptin (n=128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization. RESULTS: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P=0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P=0.07). CONCLUSIONS: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.

DOI PubMed

血清尿酸値は女性において収縮期血圧の経時的な上昇と関連する 線形混合効果モデルでの解析

森 和真, 田中 希尚, 東浦 幸村, 小山 雅之, 塙 なぎさ, 大西 浩文, 古橋 眞人

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 )  55回   86 - 86  2022年01月

尿酸とCOVID-19の原因ウイルスSARS-CoV-2の宿主側受容体ACE2との関連についての検討

古橋 眞人, 田中 希尚, 東浦 幸村, 森 和真, 小山 雅之, 大西 浩文, 齋藤 重幸, 島本 和明

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 )  55回   80 - 80  2022年01月

血清尿酸値は女性において収縮期血圧の経時的な上昇と関連する 線形混合効果モデルでの解析

森 和真, 田中 希尚, 東浦 幸村, 小山 雅之, 塙 なぎさ, 大西 浩文, 古橋 眞人

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 )  55回   86 - 86  2022年01月

尿酸とCOVID-19の原因ウイルスSARS-CoV-2の宿主側受容体ACE2との関連についての検討

古橋 眞人, 田中 希尚, 東浦 幸村, 森 和真, 小山 雅之, 大西 浩文, 齋藤 重幸, 島本 和明

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 )  55回   80 - 80  2022年01月

Circulating level of FABP4 is an independent predictor of metabolic dysfunction‐associated fatty liver disease in middle‐aged and elderly individuals

Marenao Tanaka, Satoko Takahashi, Yukimura Higashiura, Akiko Sakai, Masayuki Koyama, Shigeyuki Saitoh, Kazuaki Shimamoto, Hirofumi Ohnishi, Masato Furuhashi

Journal of Diabetes Investigation ( Wiley )   2021年12月

DOI

Fatty liver index is independently associated with deterioration of renal function during a 10-year period in healthy subjects

Satoko Takahashi, Marenao Tanaka, Masato Furuhashi, Norihito Moniwa, Masayuki Koyama, Yukimura Higashiura, Arata Osanami, Yufu Gocho, Hirofumi Ohnishi, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Tetsuji Miura

Scientific Reports ( Springer Science and Business Media {LLC} )  11 ( 1 )  2021年12月

　概要を見る

AbstractA potential link between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) has been suggested. We investigated the relationship between fatty liver index (FLI), a noninvasive and simple predictor of NAFLD, and the development of CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or positive for urinary protein during a 10-year follow-up period in subjects who received annual health examinations (n = 28,890). After exclusion of CKD at baseline, a total of 14,163 subjects (male/female: 9077/5086) were recruited. During the 10-year period, 1458 males (16.1%) and 737 females (14.5%) had new onset of CKD. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of CKD development increased with a higher FLI at baseline in both males and females after adjustment of confounders. When divided by tertiles of FLI level at baseline (T1 ~ T3), the adjusted risk of CKD development in the T3 group (HR [95% confidence interval], male/female: 1.33 [1.16–1.54]/1.33 [1.08–1.63]) was significantly higher than that in both sexes in the T1 group as the reference. The addition of FLI into traditional risk factors significantly improved the discriminatory capability for predicting CKD. In conclusion, a high level of FLI predicts the development of CKD in both sexes in a general population.

DOI

High level of fatty liver index predicts new onset of diabetes mellitus during a 10-year period in healthy subjects

Yukimura Higashiura, Masato Furuhashi, Marenao Tanaka, Satoko Takahashi, Masayuki Koyama, Hirofumi Ohnishi, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Norihito Moniwa, Kazufumi Tsuchihashi, Tetsuji Miura

Scientific Reports ( Springer Science and Business Media {LLC} )  11 ( 1 )  2021年12月

　概要を見る

AbstractFatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. This study aimed to evaluate the relationship between FLI and new onset of diabetes mellitus (DM). We investigated the association of FLI with new onset of DM during a 10-year period in subjects who received annual health examinations (n = 28,990). After exclusion of subjects with DM at baseline and those with missing data, a total of 12,290 subjects (male/female: 7925/4365) who received health examinations were recruited. FLI was significantly higher in males than in females. During the 10-year period, DM was developed in 533 males (6.7%) and 128 females (2.9%). Multivariable Cox proportional hazard models with a restricted cubic spline showed that the risk of new onset of DM increased with a higher FLI at baseline in both sexes after adjustment of age, fasting plasma glucose, habits of alcohol drinking and current smoking, family history of DM and diagnosis of hypertension and dyslipidemia at baseline. When the subjects were divided into subgroups according to tertiles of FLI level at baseline (T1–T3) in the absence and presence of impaired fasting glucose (IFG), hazard ratios after adjustment of the confounders gradually increased from T1 to T3 and from the absence to presence of IFG in both male and female subjects. In conclusion, a high level of FLI predicts new onset of DM in a general population of both male and female individuals.

DOI

Detection of significantly high vitreous concentrations of fatty acid-binding protein 4 in patients with proliferative diabetic retinopathy

Kaku Itoh, Masato Furuhashi, Yosuke Ida, Hiroshi Ohguro, Megumi Watanabe, Soma Suzuki, Fumihito Hikage

Scientific Reports ( Springer Science and Business Media {LLC} )  11 ( 1 )  2021年12月

　概要を見る

AbstractThe fatty acid-binding protein4 (FABP4) and vascular endothelial growth factor A (VEGFA) play key roles in the metabolic and cardiovascular diseases, and proliferative diabetic retinopathy (PDR), respectively. To identify FABP4 in vitreous fluid in PDR, vitreous concentrations of FABP4 (V-FABP4) and VEGFA (V-VEGFA) from PDR (n = 20) and non-PDR (n = 20) patients were determined by Enzyme-Linked ImmunoSorbent Assays. The data, which included height and weight, systemic blood pressures, several blood biochemical parameters and blood flow at the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) were collected. The levels of V-FABP4 and V-VEGFA were significantly higher in PDR patients than in non-PDR patients (P < 0.001) with a high positive correlation (r = 0.72, P < 0.001) between them. The findings were not affected by body mass index values and the presence of vitreous hemorrhaging. Among the clinical parameters, V-FABP4 correlated positively with creatinine and negatively with age and aspartate transaminase (AST) levels, while V-VEGFA correlated positively with fasting plasma glucose and hemoglobin A1c (HbA1c) levels but negatively with AST. Multiple regression analyses indicated that V-VEGFA, or V-FABP4, AST and HbA1c were independent predictors of V-FABP4 or V-VEGFA, respectively. Both were negatively correlated, but more evident in V-FABP4, with the ONH ocular blood flow.

DOI

Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study

Norie Saito, Masato Furuhashi, Masayuki Koyama, Yukimura Higashiura, Hiroshi Akasaka, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Nobuyuki Ura, Kazuaki Shimamoto, Tetsuji Miura

Scientific Reports ( Springer Science and Business Media {LLC} )  11 ( 1 ) OJ16 - 4  2021年12月

　概要を見る

AbstractFatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1–T3), Kaplan–Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20–22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.

DOI

Serum uric acid level is associated with an increase in systolic blood pressure over time in female subjects: Linear mixed-effects model analyses

Kazuma Mori, Masato Furuhashi, Marenao Tanaka, Yukimura Higashiura, Masayuki Koyama, Nagisa Hanawa, Hirofumi Ohnishi

Hypertension Research ( Springer Science and Business Media LLC )   2021年11月

DOI

Pan-rock and rock2 inhibitors affect dexamethasone-treated 2d-and 3d-cultured human trabecular meshwork (Htm) cells in opposite manners

Megumi Watanabe, Yosuke Ida, Masato Furuhashi, Yuri Tsugeno, Fumihito Hikage, Hiroshi Ohguro

Molecules ( MDPI )  26 ( 21 )  2021年11月

　概要を見る

Effects of a pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025 on dex-amethasone (DEX)-treated human trabecular meshwork (HTM) cells as a model of steroid-induced glaucoma were investigated. In the presence of Rip or KD025, DEX-treated HTM cells were subjected to permeability analysis of 2D monolayer by transendothelial electrical resistance (TEER) and FITC– dextran permeability, physical properties, size and stiffness analysis (3D), and qPCR of extracellular matrix (ECM), and their modulators. DEX resulted in a significant increase in the permeability, as well as a large and stiff 3D spheroid, and those effects were inhibited by Rip. In contrast, KD025 exerted opposite effects on the physical properties (down-sizing and softening). Furthermore, DEX induced several changes of gene expressions of ECM and their modulators were also modulated differently by Rip and KD025. The present findings indicate that Rip and KD025 induced opposite effects toward 2D and 3D cell cultures of DEX-treated HTM cells.

DOI

Autotaxin may have lysophosphatidic acid-unrelated effects on three-dimension (3d) cultured human trabecular meshwork (htm) cells

Megumi Watanabe, Masato Furuhashi, Yuri Tsugeno, Yosuke Ida, Fumihito Hikage, Hiroshi Ohguro

International Journal of Molecular Sciences ( MDPI )  22 ( 21 )  2021年11月

　概要を見る

Purpose: The objective of the current study was to evaluate the effects of the autotaxin (ATX)–lysophosphatidic acid (LPA) signaling axis on the human trabecular meshwork (HTM) in two-dimensional (2D) and three-dimensional (3D) cultures of HTM cells. Methods: The effects were characterized by transendothelial electrical resistance (TEER) and FITC-dextran permeability (2D), measurements of size and stiffness (3D), and the expression of several genes, including extracellular matrix (ECM) molecules, their modulators, and endoplasmic reticulum (ER) stress-related factors. Results: A one-day exposure to 200 nM LPA induced significant down-sizing effects of the 3D HTM spheroids, and these effects were enhanced slightly on longer exposure. The TEER and FITC-dextran permeability data indicate that LPA induced an increase in the barrier function of the 2D HTM monolayers. A one-day exposure to a 2 mg/L solution of ATX also resulted in a significant decrease in the sizes of the 3D HTM spheroids, and an increase in stiffness was also observed. The gene expression of several ECMs, their regulators and ER-stress related factors by the 3D HTM spheroids were altered by both ATX and LPA, but in different manners. Conclusions: The findings presented herein suggest that ATX may have additional roles in the human TM, in addition to the ATX–LPA signaling axis.

DOI

Fatty Liver Index(FLI)は新規高血圧発症の独立した予測因子である

東浦 幸村, 古橋 眞人, 田中 希尚, 高橋 聖子, 山下 智久, 小山 雅之, 大西 浩文, 斎藤 重幸, 三浦 哲嗣, 塙 なぎさ

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 )  43回   217 - 217  2021年10月

一般住民におけるFatty Liver Index(FLI)と高血圧発症との関連

東浦 幸村, 古橋 眞人, 田中 希尚, 大西 浩文, 三浦 哲嗣

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 )  53回   186 - 186  2021年10月

Fatty Liver Index(FLI)は新規高血圧発症の独立した予測因子である

東浦 幸村, 古橋 眞人, 田中 希尚, 高橋 聖子, 山下 智久, 小山 雅之, 大西 浩文, 斎藤 重幸, 三浦 哲嗣, 塙 なぎさ

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 )  43回   217 - 217  2021年10月

一般住民におけるFatty Liver Index(FLI)と高血圧発症との関連

東浦 幸村, 古橋 眞人, 田中 希尚, 大西 浩文, 三浦 哲嗣

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 )  53回   186 - 186  2021年10月