論文 - 大西　浩文

ALT、γGTPの組み合わせによる糖尿病発症リスク評価の向上

宮森 大輔, 田中 希尚, 古橋 眞人, 茂庭 仁人, 三浦 哲嗣, 小山 雅之, 大西 浩文, 沼田 啓太, 久末 章史, 塙 なぎさ

日本内科学会雑誌 ( (一社)日本内科学会 )  109 ( Suppl. ) 241 - 241  2020年02月

ALT、γGTPの組み合わせによる糖尿病発症リスク評価の向上

宮森 大輔, 田中 希尚, 古橋 眞人, 茂庭 仁人, 三浦 哲嗣, 小山 雅之, 大西 浩文, 沼田 啓太, 久末 章史, 塙 なぎさ

日本内科学会雑誌 ( (一社)日本内科学会 )  109 ( Suppl. ) 241 - 241  2020年02月

Differential regulation of hypoxanthine and xanthine by obesity in a general population.

Masato Furuhashi, Masayuki Koyama, Yukimura Higashiura, Takayo Murase, Takashi Nakamura, Megumi Matsumoto, Akiko Sakai, Hirofumi Ohnishi, Marenao Tanaka, Shigeyuki Saitoh, Norihito Moniwa, Kazuaki Shimamoto, Tetsuji Miura

Journal of diabetes investigation   11 ( 4 ) 878 - 887  2020年01月  [査読有り]  [国内誌]

　概要を見る

AIMS/INTRODUCTION: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. MATERIALS AND METHODS: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. RESULTS: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. CONCLUSIONS: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

DOI PubMed

一般住民においてヒポキサンチンとキサンチンの血中濃度は肥満によって異なった制御を受ける

古橋 眞人, 東浦 幸村, 小山 雅之, 村瀬 貴代, 中村 敬志, 酒井 晶子, 田中 希尚, 茂庭 仁人, 大西 浩文, 斎藤 重幸, 三浦 哲嗣

日本痛風・核酸代謝学会総会プログラム抄録集 ( (一社)日本痛風・尿酸核酸学会 )  53回   74 - 74  2020年01月

Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study.

Hime Suzuki, Nobuhiro Mikuni, Hirofumi Ohnishi, Rintaro Yokoyama, Rei Enatsu, Satoko Ochi

PloS one   15 ( 10 ) e0240082  2020年  [国際誌]

　概要を見る

OBJECTIVES: To evaluate the effects of nonadherence to antiseizure medications (ASMs) and clinical characteristics on seizure control, we employed a prospective cohort cross-sectional study using self-reports and medical records of patients with epilepsy (PWEs). METHODS: Eight hundred and fifty-five PWEs taking ASMs were enrolled from fourteen collaborative outpatient clinics from January 2018 to March 2019. Questions from the Morisky Medication Adherence Scale were used as adherence self-reports. If a PWE's questionnaire indicated that they had missed doses of their ASMs, outpatient physicians asked them directly about the details of their compliance, including the timing of intentionally or unintentionally missed doses. The association between lack of seizure control and utilization outcomes, such as missed doses, demographics, and clinical characteristics of the PWEs, were assessed by univariate and multivariate analyses. RESULTS: Multivariate analysis revealed that forgetting to take ASMs was associated with lack of seizure control and the existence of focal to bilateral tonic-clonic seizures. Dementia, younger age, use of three or more antiepileptic agents, and living in a one-person household were associated with the risk of forgetting to take ASMs. SIGNIFICANCE: For PWEs with poor drug management or a high incidence of missed doses of ASMs, efforts to improve adherence could facilitate better seizure control and decrease focal to bilateral tonic-clonic propagation.

DOI PubMed

Lower limb muscle mass is associated with insulin resistance more than lower limb muscle strength in non-diabetic older adults.

Toshiaki Seko, Hiroshi Akasaka, Masayuki Koyama, Nobuaki Himuro, Shigeyuki Saitoh, Tetsuji Miura, Mitsuru Mori, Hirofumi Ohnishi

Geriatrics & gerontology international   19 ( 12 ) 1254 - 1259  2019年12月  [査読有り]  [国内誌]

　概要を見る

AIM: We examined the association of muscle mass and muscle strength with insulin resistance, focusing on lower limb muscles. METHODS: This was a cross-sectional study, and participants were registered in 2017 from the Tanno-Sobetsu Study, a population-based cohort study. After excluding individuals aged <64 years or with a history of diabetes mellitus, 272 non-diabetic older adults (116 men, 156 women) met the inclusion criteria. According to the homeostasis model assessment of insulin resistance, the participants were divided into two groups; that is, the insulin resistance group (homeostasis model assessment of insulin resistance ≥1.73) and non-insulin resistance group (homeostasis model assessment of insulin resistance <1.73). Muscle mass (lower limb, upper limb, appendicular and trunk) and muscle strength (grip strength and knee extension torque) were measured and divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). The adjusted odds ratio (OR) of each muscle index for risk of insulin resistance was calculated separately for both men and women. RESULTS: Lower limb muscle mass (OR 0.72, 95% CI 0.55-0.92 in men; OR 0.69, 95% CI 0.51-0.96 in women, respectively) and appendicular muscle mass (OR 0.75, 95% CI 0.61-0.94 in men; OR 0.72, 95% CI 0.54-0.95 in women, respectively), but not other muscle indexes, were associated with risk of insulin resistance, after adjusting for age, body mass index, highly sensitive C-reacting protein and smoking habits. CONCLUSIONS: Lower limb muscle mass of non-diabetic older adults is independently related to insulin resistance. Geriatr Gerontol Int 2019; 19: 1254-1259.

DOI PubMed

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

Sato T, Miki T, Furukawa S, Matsuura B, Hiasa Y, Ohnishi H, Tanno M, Miura T

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

　概要を見る

QTc dispersion (QTcd) tended to be decreased at 24 weeks and was significantly decreased at 2 years after dapagliflozin treatment. In the subgroup with QTcd?53.7 ms (median), QTcd was significantly decreased at 24 weeks and remained improved for 2 years. Dapagliflozin also significantly reduced Tpeak-Tend/QT in a subgroup with Tpeak-Tend/QT?0.25 (median).

DOI PubMed

一般住民において血漿ヒポキサンチン濃度は肥満度および喫煙と関連する

東浦 幸村, 古橋 眞人, 松本 めぐみ, 酒井 晶子, 小山 雅之, 村瀬 貴代, 中村 敬志, 田中 希尚, 茂庭 仁人, 大西 浩文, 斎藤 重幸, 三浦 哲嗣

肥満研究 ( (一社)日本肥満学会 )  25 ( Suppl. ) 279 - 279  2019年10月

外国人患者の当院受療時ニーズに関する社会疫学的調査(第2報)

鈴村 美和, 菅原 誠, 鈴村 滋生, 森 満, 大西 浩文

日本公衆衛生学会総会抄録集 ( 日本公衆衛生学会 )  78回   589 - 589  2019年10月

一般住民におけるキサンチン酸化還元酵素(XOR)活性と高血圧との関連

東浦 幸村, 古橋 眞人, 小山 雅之, 田中 希尚, 茂庭 仁人, 松本 めぐみ, 酒井 晶子, 村瀬 貴代, 中村 敬志, 大西 浩文, 齋藤 重幸, 島本 和明, 三浦 哲嗣

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 )  42回   279 - 279  2019年10月

北海道都市部健診受診者コホートにおける初年度の血圧カテゴリ別の血清尿酸値と高血圧発症との関連

小山 雅之, 樋室 伸顕, 田中 希尚, 茂庭 仁人, 古橋 眞人, 沼田 啓太, 久末 章史, 塙 なぎさ, 齋藤 重幸, 三浦 哲嗣, 大西 浩文

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 )  42回   300 - 300  2019年10月

Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight.

Masato Furuhashi, Masayuki Koyama, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Yukimura Higashiura, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Endocrine journal   66 ( 9 ) 777 - 786  2019年09月  [査読有り]  [国内誌]

　概要を見る

Xanthine oxidoreductase (XOR), an enzyme of uric acid formation from hypoxanthine and xanthine, is recognized as a source of oxidative stress. Plasma activity of XOR has been reported to be a biomarker of metabolic disorders associated with obesity, liver dysfunction, insulin resistance, hyperuricemia and adipokines. We investigated longitudinal change in plasma XOR activity, which was determined by using mass spectrometry and liquid chromatography to detect [13C2, 15N2]-uric acid using [13C2, 15N2]-xanthine as a substrate, in 511 subjects (male/female: 244/267) of the Tanno-Sobetsu Study in the years 2016 and 2017. Plasma XOR activity in a basal state was significantly higher in men than in women, but no significant sex difference was observed in annual change in plasma XOR activity. Annual change in plasma activity of XOR was positively correlated with changes in each parameter, including body weight (r = 0.203, p < 0.001), body mass index, diastolic blood pressure, aspartate transaminase (AST) (r = 0.772, p < 0.001), alanine transaminase (r = 0.647, p < 0.001), γ-glutamyl transpeptidase, total cholesterol, triglycerides, uric acid, fasting glucose and HbA1c. Multivariate regression analysis demonstrated that change in AST and that in body weight were independent predictors of change in plasma XOR activity after adjustment of age, sex and changes in each variable with a significant correlation without multicollinearity. In conclusion, annual change in plasma XOR activity is independently associated with changes in liver enzymes and body weight in a general population. Improvement of liver function and reduction of body weight would decrease plasma XOR activity and its related oxidative stress as a therapeutic strategy.

DOI PubMed

Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects.

Tamaki Matsumoto, Hirofumi Ohnishi, Tatsuya Sato, Takayuki Miki, Hiroshi Akasaka, Nagisa Hanawa, Masayuki Koyama, Shigeyuki Saitoh, Tetsuji Miura

Cardiology and therapy   8 ( 2 ) 239 - 251  2019年07月  [査読有り]  [国際誌]

　概要を見る

INTRODUCTION: Increased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects. METHODS: The study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak-Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box-Cox transformation. RESULTS: In longitudinal analyses, Box-Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n = 153, r = - 0.207, 95% CI - 0.354 to - 0.050, p = 0.010) and with log TG/HDL-C at baseline in cohort 2 (n = 738, r = - 0.098, 95% CI - 0.169 to - 0.026, p = 0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters. CONCLUSION: Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.

DOI PubMed

日本の大規模コホートによる糖尿病と高血圧が心血管疾患による死亡の生涯リスクに与える影響 The EPOCH-JAPAN study

今井 由希子, 平田 匠, 斎藤 重幸, 二宮 利治, 宮本 恵宏, 大西 浩文, 磯 博康, 三浦 克之, 玉腰 暁子, 山田 美智子, 木山 昌彦, 石川 鎮清, 岡村 智教

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 )  51回   2 - 5  2019年07月  [査読有り]

【診療ガイドラインの読み方ガイダンス】循環器領域での診療ガイドライン作成経験 システマティックレビューチームの役割

樋室 伸顕, 大西 浩文

泌尿器外科 ( 医学図書出版(株) )  32 ( 7 ) 927 - 931  2019年07月

　概要を見る

高血圧治療ガイドライン2019の作成において、システマティックレビューチームの一員としてひとつのClinical Question(CQ)に対するシステマティックレビューを担当した。Mindsの「診療ガイドライン作成マニュアル」に従い作業を進めたが、スクリーニングは慎重な作業が求められ、エビデンス評価はその判定基準に悩むことが多い。一方CQに関する論文を網羅的に読むのでその分野の専門家になることができる。(著者抄録)

【JSH2019改訂における重要ポイント(3)糖尿病合併高血圧】降圧薬選択に関するシステマティックレビュー

大西 浩文, 国村 彩子, 樋室 伸顕, 瀬川 裕佳, 藤吉 朗, 斎藤 重幸

血圧 ( (株)先端医学社 )  26 ( 7 ) 397 - 405  2019年07月

　概要を見る

今回、高血圧治療ガイドライン2019の策定にあたって、「糖尿病合併高血圧の降圧治療では、Ca拮抗薬、サイアザイド系利尿薬よりも、ARB、ACE阻害薬を優先するべきか」を明らかにするためのシステマティックレビューおよびメタアナリシスをおこなった。16件のRCTに基づいて検討をおこなうと、死亡や心血管疾患イベント、腎機能障害リスク低減効果についてレニン・アンジオテンシン(RA)系阻害薬の他の薬剤に対する明らかな優位性は示されなかった。結果の解釈には注意を要するものの、糖尿病合併高血圧患者における第一選択薬としては、ARB、ACE阻害薬のみならず、Ca拮抗薬、サイアザイド系利尿薬も推奨され得ると考えられた。(著者抄録)

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines.

Masato Furuhashi, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Journal of diabetes investigation   10 ( 4 ) 1059 - 1067  2019年07月  [査読有り]  [国内誌]

　概要を見る

AIMS/INTRODUCTION: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance. MATERIALS AND METHODS: The association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid-binding protein 4 (FABP4) and fibroblast growth factor 21 (FGF21), was investigated in 282 participants (male/female: 126/156) of the Tanno-Sobetsu Study who were not taking medication. RESULTS: Women had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP4 (r = 0.192, P < 0.001) and FGF21 (r = 0.208, P < 0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level (r = -0.243, P = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP4 and FGF21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP4, but not that of adiponectin or FGF21, remained as an independent predictor of plasma XOR activity. CONCLUSIONS: Plasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.

DOI PubMed

The effects of renin–angiotensin system inhibitors on mortality, cardiovascular events, and renal events in hypertensive patients with diabetes: a systematic review and meta-analysis of randomized controlled trials

Kunimura A, Himuro N, Fujiyoshi A, Segawa H, Ohnishi H, Saitoh S

Hypertension Research   42 ( 5 ) 669 - 680  2019年04月  [査読有り]  [国際誌]

　概要を見る

Renin-angiotensin system (RAS) inhibitors are often used as a first-line treatment for hypertensive patients with diabetes because of purported benefits, such as reno-protection. However, there is no clear evidence for the superiority of RAS inhibitors to other classes of antihypertensives for clinically important outcomes in this population. We conducted a meta-analysis to assess whether RAS inhibitors are better than other classes of antihypertensives for reducing mortality, and cardiovascular and renal events in hypertensive patients with diabetes. From June to December 2017, we searched Medline, Cochrane Library, and the database of the Japan Medical Abstracts Society (ICHUSHI) for relevant published randomized controlled trials that directly compared the effects of RAS inhibitors to other classes of antihypertensives as first-line treatments for reducing adverse outcomes among hypertensive patients with diabetes. Our predetermined outcomes included all-cause death, cardiovascular death, incidence of cardiovascular disease, and renal dysfunction. We identified 16 trials, including a total of 35,052 patients. No significant benefits for RAS inhibitors were found compared to other classes of antihypertensives for all-cause death (relative risk (RR) 0.95, 95% confidence interval (CI) 0.85-1.05, p = 0.29), cardiovascular death (RR 0.84, 95% CI 0.68-1.04, p = 0.11), incidence of cardiovascular disease (RR 0.93, 95% CI 0.84-1.03, p = 0.16), and incidence of renal dysfunction (RR 0.91, 95% CI 0.77-1.06, p = 0.22). In conclusion, RAS inhibitors are not superior to other classes of antihypertensive drugs for reducing all-cause and cardiovascular mortalities, cardiovascular events, and renal events in hypertensive patients with diabetes.

DOI PubMed

2型糖尿病患者の心筋再分極不均一に対するdapagliflozinの経時的効果

佐藤 達也, 大西 浩文, 三木 隆幸, 古川 慎哉, 松浦 文三, 日浅 陽一, 三浦 哲嗣

糖尿病 ( (一社)日本糖尿病学会 )  62 ( Suppl.1 ) S - 228  2019年04月

心血管イベントに対する高リスク糖尿病患者を検出するためのECG検査の重要性とSGLT2阻害剤による利点

三木隆幸, 佐藤達也, 大西浩文, 矢野俊之, 中田圭, 丹野雅也, 三浦哲嗣

日本循環器学会学術集会(Web) ( (一社)日本循環器学会 )  83回   SY12 - 3  2019年03月

J-GLOBAL