論文 - 益崎　裕章

糖尿病腎症ステージ毎の血糖変動指標の検討

澤紙 亜希子, 比嘉 盛丈, 盛島 菜美, 座覇 明子, 眞境名 豊文, 當眞 武, 渡邊 桐子, 田辺 隼人, 待井 典剛, 益崎 裕章, 島袋 充生

糖尿病 ( (一社)日本糖尿病学会 )  63 ( Suppl.1 ) S - 343   2020年08月

掲載種別: 研究論文（その他学術会議資料等）

Walking Speed is the Sole Determinant Criterion of Sarcopenia of Mild Cognitive Impairment in Japanese Elderly Patients with Type 2 Diabetes Mellitus.

Machii N, Kudo A, Saito H, Tanabe H, Iwasaki M, Hirai H, Masuzaki H, Shimabukuro M

Journal of clinical medicine ( Journal of Clinical Medicine )  9 ( 7 ) 1 - 17   2020年07月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

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Factors Associated with Risk of Diabetic Complications in Novel Cluster-Based Diabetes Subgroups: A Japanese Retrospective Cohort Study.

Tanabe H, Saito H, Kudo A, Machii N, Hirai H, Maimaituxun G, Tanaka K, Masuzaki H, Watanabe T, Asahi K, Kazama J, Shimabukuro M

Journal of clinical medicine   9 ( 7 )   2020年07月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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満足できない肥満脳のメカニズム解析

岡本 士毅, 箕越 靖彦, 益崎 裕章

メタボリックシンドローム ( 高尿酸血症・メタボリックシンドロームリサーチフォーラム )  16 ( 1 ) 2 - 5   2020年07月

掲載種別: 研究論文（その他学術会議資料等）

ヒト生検検体を用いた腎臓周囲と皮下の脂肪組織におけるアディポネクチン発現量とその決定因子(Levels of Adiponectin Expression in Peri-Renal and Subcutaneous Adipose Tissue and Its Determinants in Human Biopsied Samples)

Maimaituxun Gulinu, 福田 大受, 井崎 博文, 平田 陽一郎, 金山 博臣, 益崎 裕章, 佐田 政隆, 島袋 充生

日本臨床分子医学会学術総会プログラム・抄録集 ( 日本臨床分子医学会 )  57回   75 - 75   2020年04月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

耐糖能障害を来した筋強直性ジストロフィー患者に対するメトホルミン療法の有効性

山城 清人, 照屋 太輝, 中山 良朗, 玉城 敦子, 屋比久 賢光, 長谷川 千穂, 吉村 蘭, 難波 豊隆, 山崎 聡, 池間 朋己, 益崎 裕章

糖尿病 ( (一社)日本糖尿病学会 )  63 ( 4 ) 291 - 292   2020年04月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

マウスにて、エクストラヴァージンオリーブオイルと亜麻仁オイルは粘膜と代謝の健全性を促進し、腸内細菌叢を調節する(Extra virgin olive and flaxseed oils modulate gut microbiota, enhancing mucosal and metabolic health in mice)

ミルマン・ジャスミン, 岡本 士毅, 木村 碧樹, 上間 次己, 比嘉 萌子, 難波 豊隆, 山崎 聡, 島袋 充生, 池松 真也, 益崎 裕章

日本臨床分子医学会学術総会プログラム・抄録集 ( 日本臨床分子医学会 )  57回   64 - 64   2020年04月

掲載種別: 研究論文（その他学術会議資料等）

Proteomic profiling of HTLV-1 carriers and ATL patients reveals sTNFR2 as a novel diagnostic biomarker for acute ATL.

Guerrero CLH, Yamashita Y, Miyara M, Imaizumi N, Kato M, Sakihama S, Hayashi M, Miyagi T, Karimata K, Uchihara J, Ohshiro K, Todoroki J, Nakachi S, Morishima S, Karube K, Tanaka Y, Masuzaki H, Fukushima T

Blood advances ( Blood Advances )  4 ( 6 ) 1062 - 1071   2020年03月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type 1 (HTLV-1)-associated T-cell malignancy with generally poor prognosis. Although only ∼5% of HTLV-1 carriers progress to ATL, early diagnosis is challenging because of the lack of ATL biomarkers. In this study, we analyzed blood plasma profiles of asymptomatic HTLV-1 carriers (ACs); untreated ATL patients, including acute, lymphoma, smoldering, and chronic types; and ATL patients in remission. Through SOMAscan, expression levels of 1305 plasma proteins were analyzed in 85 samples (AC, n = 40; ATL, n = 40; remission, n = 5). Using gene set enrichment analysis and gene ontology, overrepresented pathways in ATL vs AC included angiogenesis, inflammation by cytokines and chemokines, interleukin-6 (IL-6)/JAK/STAT3, and notch signaling. In selecting candidate biomarkers, we focused on soluble tumor necrosis factor 2 (sTNFR2) because of its active role in enriched pathways, extreme significance (Welch's t test P < .00001), high discrimination capacity (area under the curve >0.90), and novelty in ATL research. Quantification of sTNFR2 in 102 plasma samples (AC, n = 30; ATL, n = 68; remission, n = 4) using enzyme-linked immunosorbent assay showed remarkable elevations in acute ATL, at least 10 times those of AC samples, and return of sTNFR2 to AC state levels after achieving remission. Flow cytometry and immunostaining validated the expression of TNFR2 in ATL cells. No correlation between sIL-2 and sTNFR2 levels in acute ATL was found, suggesting the possibility of sTNFR2 as an independent biomarker. Our findings represent the first extensive blood-based proteomic analysis of ATL, suggesting the potential clinical utility of sTNFR2 in diagnosing acute ATL.

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糞線虫症はアグレッシブ成人T細胞白血病リンパ腫に影響を与えるか? 沖縄県アグレッシブATLデータベースの解析

玉城 啓太, 森島 聡子, 野村 尚吾, 西 由希子, 仲地 佐和子, 福島 卓也, 益崎 裕章

沖縄県医師会報 ( (一社)沖縄県医師会 )  56 ( 3 ) 202 - 207   2020年03月

掲載種別: 研究論文（その他学術会議資料等）

　概要を見る

播種性糞線虫症は成人T細胞白血病リンパ腫(ATL)における致死的合併症のひとつであり、ATLの予後不良因子と見做されてきたが、病態的意義の詳細は明らかでなかった。ATLの予後因子としての糞線虫症の意義と既存の二つの予後指標(ATL-PI、JCOG-PI)の有用性を沖縄県アグレッシブATLデータベースから抽出した433例で後方視的に検証した。主要評価項目は全生存期間(OS)とし、ログランク検定やCox回帰分析を用いて糞線虫症のOSへの影響を評価した。糞線虫症は便検査で診断した。全体の生存期間中央値は0.5年、3年生存割合は12.3%であった。糞線虫症は陽性55例、陰性378例であった。単変量解析で糞線虫症はOSに影響せず(ハザード比1.22;95%信頼区間0.90-1.66)、3年生存割合でも差を認めなかった(陽性群:8.2% vs 陰性群:13.0%、P=0.20)。本研究により、ATL-PIがリスク層別化に優れていること、初期の予想に反して糞線虫症はアグレッシブATLの予後に影響しない可能性が示唆された。(著者抄録)

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing.

Yotsumoto J, Sekizawa A, Inoue S, Suzumori N, Samura O, Yamada T, Miura K, Masuzaki H, Sawai H, Murotsuki J, Hamanoue H, Kamei Y, Endo T, Fukushima A, Katagiri Y, Takeshita N, Ogawa M, Nishizawa H, Okamoto Y, Tairaku S, Kaji T, Maeda K, Matsubara K, Ogawa M, Osada H, Ohba T, Kawano Y, Sasaki A, Sago H, Japan NIPT Consortium

BMC pregnancy and childbirth   20 ( 1 ) 112   2020年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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特集 高血圧診療Update-「高血圧治療ガイドライン2019」で何が変わるのか? 他疾患を合併する高血圧 肥満症・メタボリックシンドローム

山崎 聡, 尾形 絵美, 岡本 士毅, 島袋 充生, 益崎 裕章

内科 ( 南江堂 )  125 ( 2 ) 227 - 230   2020年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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The Incidence of Dichorionic Diamniotic Twin Pregnancy After Single Blastocyst Embryo Transfer and Zygosity: 8 Years of Single-Center Experience.

Konno H, Murakoshi T, Miura K, Masuzaki H

Twin research and human genetics : the official journal of the International Society for Twin Studies   23 ( 1 ) 51 - 54   2020年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction.

Maimaituxun G, Yamada H, Fukuda D, Yagi S, Kusunose K, Hirata Y, Nishio S, Soeki T, Masuzaki H, Sata M, Shimabukuro M

Circulation journal : official journal of the Japanese Circulation Society ( 一般社団法人 日本循環器学会 )  84 ( 2 ) 203 - 216   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

<p><b><i>Background:</i></b>Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).</p><p><b><i>Methods and Results:</i></b>From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EAT_RCA), left anterior descending artery (EAT_LAD), left circumflex artery (EAT_LCX), right ventricle (EAT_RV), left ventricle (EAT_LV), right atrium (EAT_RA), and left atrium (EAT_LA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m², P=0.010), EAT_LCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EAT_LV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EAT_LCXand EAT_LVwere markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EAT_LCXand EAT_LVwere strongly associated with LV diastolic function parameters.</p><p><b><i>Conclusions:</i></b>Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.</p>

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Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction

Gulinu Maimaituxun, Hirotsugu Yamada, Daiju Fukuda, Shusuke Yagi, Kenya Kusunose, Yukina Hirata, Susumu Nishio, Takeshi Soeki, Hiroaki Masuzaki, Masataka Sata, Michio Shimabukuro

Circulation Journal ( Japanese Circulation Society )  84 ( 2 ) 203 - 216   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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A combination of dietary fat intake and nicotine exposure enhances CB1 endocannabinoid receptor expression in hypothalamic nuclei in male mice.

Guo T, Tanaka T, Matsumoto M, Kaneko K, Unzai T, Ogino Y, Aotani D, Kusakabe T, Iwakura H, Miyazawa T, Sawamoto K, Minokoshi Y, Masuzaki H, Inagaki N, Nakao K

Neuroscience letters ( Neuroscience Letters )  714   134550 - 134550   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

BACKGROUND: Cannabinoid receptor 1 (CB1R) is a GPCR expressed widely in the brain as well as in peripheral metabolic organs. Although pharmacological blockade of CB1R has been effective for the treatment of obesity and tobacco addiction, precise distribution of CB1R within the brain and potential changes by obesity or nicotine exposure have not been thoroughly addressed. METHODS: To examine CB1R distribution within the central energy center, we performed immunostaining and qPCR analysis of micro-dissected hypothalamic nuclei from male C57BL/6 mice. To address the effect of nicotine on food intake and body weight, and on potential changes of CB1R levels in the hypothalamus, mice kept on a high fat diet (HFD) for four weeks were challenged with nicotine intraperitoneally. RESULTS: Validity of the micro-dissected samples was confirmed by the expression of established nucleus-enriched genes. The expression levels of CB1R in the arcuate and lateral nuclei of the hypothalamus were higher than paraventricular and ventral-dorsal medial nuclei. Nicotine administration led to a significant suppression of food intake and body weight either under standard or high fat diet. Neither HFD nor nicotine alone altered CB1R levels in any nucleus tested. By contrast, treatment of HFD-fed mice with nicotine led to a significant increase in CB1R levels in the arcuate, paraventricular and lateral nuclei. CONCLUSIONS: CB1R was widely distributed in multiple hypothalamic nuclei. The expression of CB1R was augmented only when mice were treated with HFD and nicotine in combination. These data suggest that the exposure to nicotine may provoke an enhanced endocannabinoid response in diet-induced obesity.

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Transplant-related complications are impediments to the success of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia patients in non-complete remission.

Tomori S, Morishima S, Nishi Y, Nakachi S, Tamaki K, Morichika K, Tedokon I, Shimabukuro N, Hanashiro T, Kitamura S, Uchibori S, Miyagi R, Miyagi T, Karimata K, Ohama M, Yamanoha A, Tomoyose T, Karube K, Fukushima T, Masuzaki H

Bone marrow transplantation ( Bone Marrow Transplantation )  55 ( 1 ) 233 - 241   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

Outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with adult T cell leukemia/lymphoma (ATL) are not satisfactory, particularly in patients in non-complete remission at transplantation (Pt-non-CR). We conducted a regional retrospective study in the ATL endemic area of Okinawa, Japan. Of 62 ATL patients, 21 received allo-HSCT in CR and 41 in non-CR. The 3-year overall survival (3yOS) rate and median survival time for the whole cohort was 25.6% and 7.7 months, respectively. The 3yOS of Pt-non-CR was significantly lower than that of patients in CR (Pt-CR) (16.8% vs. 43.6%, P = 0.005). Transplant-related mortality (TRM) was significantly higher in Pt-non-CR than in Pt-CR (46.3% vs. 15.7%, P = 0.025), while there was no significant difference in disease-associated mortality (DAM) between Pt-non-CR and Pt-CR. Multivariable analysis for Pt-non-CR revealed that poor performance status (poor-PS) and higher sIL-2R level (high sIL-2R) adversely affected OS. Poor-PS was associated with higher TRM, but not with higher DAM in Pt-non-CR. High sIL-2R did not affect TRM or DAM in Pt-non-CR. Overall, high TRM rates rather than DAM contribute to the poor outcomes of Pt-non-CR, suggesting that not only disease control but also management of transplant-related complications is required for allo-HSCT in ATL patients.

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Impaired early-phase suppression of glucagon secretion after glucose load is associated with insulin requirement during pregnancy in gestational diabetes.

Horie I, Haraguchi A, Ito A, Nozaki A, Natsuda S, Akazawa S, Mori Y, Ando T, Higashijima A, Hasegawa Y, Yoshida A, Miura K, Masuzaki H, Kawakami A, Abiru N

Journal of diabetes investigation   11 ( 1 ) 232 - 240   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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Significance of p53-Binding Protein 1 Nuclear Foci in Cervical Squamous Intraepithelial Lesions: Association With High-Risk Human Papillomavirus Infection and P16(INK4a) Expression.

Kawashita S, Matsuda K, Kondo H, Kitajima Y, Hasegawa Y, Shimada T, Kitajima M, Miura K, Nakashima M, Masuzaki H

Cancer control : journal of the Moffitt Cancer Center   27 ( 1 ) 1073274819901170   2020年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

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人生100年時代の健康長寿の展望と課題:～沖縄クライシスからのレッスン～

益崎 裕章

理学療法学Supplement ( 公益社団法人 日本理学療法士協会 )  47 ( 0 ) G - 10-G-10   2020年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

<p>　世界に冠たる健康長寿を誇ってきた沖縄県は現在，2型糖尿病や肥満症が蔓延し，65歳までに死亡する割合（早逝率）や糖尿病患者の血液透析導入率は全国トップレベルにあります。2017年の47都道府県平均寿命ランキングでは沖縄県の男性が36位，女性が7位にまで後退しており，この驚くべき現実を私達，琉球大学第二内科で"沖縄クライシス"と命名し，この10年間，その実態解明と啓発に取り組んできました。日本で最後の国立大学医学部として琉球大学医学部が新設された1980年当時の80歳台，90歳台の沖縄県民患者の解剖所見によると，大動脈や冠状動脈の粥状動脈硬化や石灰化が殆ど認められず，血管年齢の若々しさに病理医たちが驚嘆した様子が記録されています。戦後の沖縄県民の脂肪エネルギー摂取比率は常に全国平均よりも5%以上上回っており，動脈硬化症の温床となる肥満症，糖尿病，脂質異常症の蔓延と平均寿命ランキングの降下が見事な好対照をなしています。</p><p>　健康に良くないと理屈ではわかっていても食べ過ぎや運動不足から脱却できないのはなぜでしょう？ 私達は2型糖尿病や肥満症の発症基盤にある"脳機能の異常"に注目し，脳科学と分子栄養学を用いて食事・運動療法の実効性を高める行動変容の分子基盤の解明に取り組んでいます。動物性脂肪の過剰摂取は脳をハッキングし，自らが必要とするエネルギー量や栄養成分を判断できない脳に変えてしまいます。このメカニズムには食欲中枢である視床下部における小胞体ストレスの上昇や幸せや歓びを受け取る報酬系におけるゲノム修飾というイヴェントが深く関わっています（Diabetologia 2017, Diabetes 2012）。また，肥満や動物性脂肪の過剰摂取に伴う脂肪細胞ホルモン，レプチンの作用不全（レプチン抵抗性）は脳内報酬系のドパミン神経に発現するレプチン受容体シグナルを介して運動欲求を低下させ，体重が増えていくほど，運動する意欲が減退してしまい，ますます太りやすくなります。運動嫌いな患者さんの脳の中ではこのようなことが生じていると考えられます。</p><p>　本講演では運動や食事と生活習慣病との関わりをめぐる最新の医学エビデンスを御紹介し，効果的な行動変容を実現するための理学療法の重要性に言及したいと思います。</p>

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Chest Computed Tomography Abnormalities and Their Relationship to the Clinical Manifestation of Respiratory Syncytial Virus Infection in a Genetically Confirmed Outbreak.

Nabeya D, Kinjo T, Parrott GL, Nakachi S, Yamashiro T, Ikemiyagi N, Arakaki W, Masuzaki H, Fujita J

Internal medicine (Tokyo, Japan) ( 一般社団法人 日本内科学会 )  59 ( 2 ) 247 - 252   2020年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

　概要を見る

<p>Studies reporting chest images of respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) in an outbreak setting and their relationship to the clinical manifestation are limited. During a genetically confirmed RSV outbreak, eight patients underwent both chest X-ray and computed tomography (CT). Among these, 5 cases had newly appearing abnormalities on CT, although chest X-ray was able to detect abnormalities in only 2 cases (40%). Although bronchial wall thickening was common, other findings and their distribution were variable, even in an outbreak setting. All patients with both a history of anticancer chemotherapy against hematological cancer and lower respiratory symptoms, such as wheezing, sputum, and hypoxemia, had abnormalities on CT, suggesting that these two factors might be important for predicting the existence of LRTI in RSV-infected patients. </p>

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