論文 - 広瀬　寛

Secular trends in blood pressure among university students in Japan over the last two decades

Adachi K., Azegami T., Sei N., Yamada-Goto N., Uchida K., Murai-Takeda A., Inokuchi M., Hayashi K., Mori M., Hirose H.

Hypertension Research 2024年

ISSN  09169636

　概要を見る

High blood pressure (BP) increases the risk of cardiovascular disease, not only among middle-aged and older adults, but also in young adults. Early interventions for high BP may prevent future organ damage. Therefore, it is essential to monitor BP trends in young adults to support this approach. During the COVID-19 pandemic, a trend of increasing BP was observed worldwide. However, young adults have not been fully evaluated. Therefore, this study examined BP trends among university students (n = 106,691) over two decades, every 5 years from 2003 to 2023, including the period before and after the COVID-19 pandemic. From 2003 to 2018, there were no notable changes in BP. However, following the COVID-19 pandemic, increased BP was observed in both men and women, with systolic BP increasing from 118.1 (SD, 14.2) mmHg in 2018 to 120.6 (SD, 12.5) mmHg in 2023 among men, and from 104.6 (SD, 11.8) mmHg to 105.1 (SD, 11.7) mmHg among women. These trends were particularly pronounced among students with normal and underweight somatotypes and among first- and second-year students. The results of the lifestyle survey showed a decrease in smoking and drinking habits, insufficient sleep, mental stress, consumption of fast food and snacks, and an increase in exercise habits. Although contributing factors to the recent increase in BP were not identified, there was an upward trend in BP among Japanese university students. It is important to carefully observe how BP trends change over the long term following the end of the COVID-19 pandemic. (Figure presented.)

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教職員健診における血清高分子量型アディポネクチン濃度の測定(CLEIA法)

広瀬 寛, 後藤 伸子, 森 正明

慶應保健研究 （慶應義塾大学保健管理センター）  39 （ 1 ） 71 - 76 2021年09月

ISSN  1340-9379

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アディポネクチン(ADPN)は脂肪細胞から分泌される善玉のホルモンで、細胞実験や動物実験で糖尿病や動脈硬化・腫瘍などを抑制し、百寿者では血中濃度が高いなど、抗加齢ホルモンとしての意義が注目されている。また、糖尿病マウスの脂肪細胞内でシステイン残基へのコハク酸結合により高分子量(HMW)型の産生が低下する機序が報告された。本研究では、40～65歳の教職員を対象に健診時に血清中のHMW-ADPN濃度を測定し、その意義を断面研究で検討した。当施設の定期健康診断を受診した40～65歳の教職員を対象に、血清HMW-ADPN濃度をCLEIA法で測定した(株式会社エスアールエルに委託)。解析対象の日本人は男性1,586名、女性1,019名(平均年齢は男性51歳、女性49歳)であった。(1)血清HMW-ADPN濃度の中央値は男性で2.6μg/mL、女性で4.9μg/mLであり、男女ともメタボリックシンドローム(MetS)群は非MetS群と比較して有意に低値であった。(2)男女とも、log[HMW-ADPN]はHDL-CやBNP、年齢とは正の相関が、BMI、腹囲、空腹時血糖、HbA1c、血清TG、赤血球数、ALT、γ-GTP、尿酸などと有意な負の相関が認められた。(3)男女ともに、運動習慣がある群の方がHMW-ADPNが高い傾向が認められた。(4)log[HMW-ADPN]を目的変数としたステップワイズ多重回帰分析では、HDL-C、尿酸、BMI、性別、BNP、γ-GTP、年齢、HbA1cの順に採択された(F≧10、P<0.0001、R2=0.417)。以上より、血清HMW-ADPN濃度はHDL-Cや女性、BNP、年齢とは正の、BMIや尿酸、γ-GTP、HbA1cとは負の、それぞれ独立して有意な関係を示した。(著者抄録)

Low birth weight is associated with decline in renal function in Japanese male and female adolescents

Murai-Takeda A., Kanda T., Azegami T., Hirose H., Inokuchi M., Tokuyama H., Wakino S., Tokumura M., Kawabe H., Mori M., Itoh H.

Clinical and Experimental Nephrology （Clinical and Experimental Nephrology）  23 （ 12 ） 1364 - 1372 2019年12月

ISSN  13421751

　概要を見る

© 2019, Japanese Society of Nephrology. Background: Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated. In this study, we investigated the sex-specific effect of LBW on renal function. Methods: Annual cross-sectional data of 2417 Japanese adolescents (males 1736; females 681), aged 15–16 years, were evaluated over 8 years (2007–2014). Results: Over the study period, mean birth weights decreased significantly in males (p < 0.01) and females (p < 0.05). Furthermore, both sexes showed significant decrease in estimated glomerular filtration rates corresponding to the birth weight reduction. The prevalence of CKD stage 2 also increased in males (from 26.0 to 32.4%, p < 0.01) and females (from 6.3 to 18.5%, p < 0.05). The incidence of CKD stage 2 was significantly related to history of LBW (males: odds ratio 1.73; 95% confidence interval 1.06–2.80; p < 0.05; females: odds ratio 3.29; 95% confidence interval 1.25–8.02; p < 0.05). Conclusions: Our data revealed that renal function and birth weight have decreased over time, in healthy Japanese adolescents. In view of the recent declining trend demonstrated by birth weight in Japan, we speculate that the prevalence of CKD might increase in the future.

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中高一貫校における2018年度の熱中症発生状況とその対応

福富 千尋, 佐藤 幸美子, 西村 知泰, 井ノ口 美香子, 広瀬 寛, 内田 敬子, 康井 洋介, 有馬 ふじ代, 後藤 伸子, 山田 茉未子, 伴 英子, 徳村 光昭, 森 正明

慶應保健研究 （慶應義塾大学保健管理センター）  37 （ 1 ） 79 - 84 2019年08月

ISSN  1340-9379

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神奈川県内の中高一貫校(男女共学)では、2018年度夏季休業中の部活動において熱中症が、校内、校外合わせて30件発生し、2017年の8件に比べて大幅に増加した。2018年度の夏は、夏季休業開始早々から、保健室において熱中症と判断される運動部生徒への対応が多く、学校は熱中症の発生を減らすために熱中症予防策を設けた。この予防策は、熱中症発生状況に応じて、教員と保健室スタッフが相談し、2回の見直しが行われた。今後の熱中症予防策を検討するため、見直しした対策ごとの熱中症発生者数と暑さ指数(Wet Bulb Globe Temperature:WBGT、湿球黒球温度)の関係を解析した。また、熱中症罹患者を対象にアンケート調査を行った。2018年度からの熱中症予防策に従い、暑さ指数を基準とした活動制限を設けたことで熱中症発生の抑制につながった。熱中症罹患者アンケート調査では、大部分の者では、個人の身体面における熱中症発症リスクや、個人レベルの予防策における問題点は認められなかった。個人の予防対策のみで熱中症発生を防止することは難しく、学校全体で予防策に取り組む必要がある。(著者抄録)

Features of and preventive measures against hypertension in the young

Kawabe H., Azegami T., Takeda A., Kanda T., Saito I., Saruta T., Hirose H.

Hypertension Research （Hypertension Research）  42 （ 7 ） 935 - 948 2019年

ISSN  09169636

　概要を見る

© 2019, The Author(s). The Japanese hypertension guidelines report that essential hypertension is detected in 1–3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one’s health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.

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Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21

Tanikawa C., Kamatani Y., Toyoshima O., Sakamoto H., Ito H., Takahashi A., Momozawa Y., Hirata M., Fuse N., Takai-Igarashi T., Shimizu A., Sasaki M., Yamaji T., Sawada N., Iwasaki M., Tsugane S., Naito M., Hishida A., Wakai K., Furusyo N., Murakami Y., Nakamura Y., Imoto I., Inazawa J., Oze I., Sato N., Tanioka F., Sugimura H., Hirose H., Yoshida T., Matsuo K., Kubo M., Matsuda K.

Cancer Science （Cancer Science）  109 （ 12 ） 4015 - 4024 2018年12月

ISSN  13479032

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© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large-scale genome-wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11-12 (rs6490061, P = 3.20 × 10 −8 with an odds ratio [OR] of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10 −10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10 −13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10 −11 ), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.

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VISCERAL FAT AREA, INSULIN RESISTANCE INDEX AND ALCOHOL INTAKE WERE RELATED TO BLOOD PRESSURE STATUS IN COMPREHENSIVE HEALTH CHECKUP

Hirose Hiroshi, Shimizu-Hirota Ryoko, Kawabe Hiroshi

JOURNAL OF HYPERTENSION 36   E100 - E101 2018年10月

ISSN  0263-6352

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高等学校における脳しんとうの管理

佐藤 幸美子, 西村 知泰, 藤 ひとみ, 牟田口 絵里, 中村 清美, 山岸 あや, 広瀬 寛, 徳村 光昭, 森 正明, 河邊 博史

慶應保健研究 （慶應義塾大学保健管理センター）  36 （ 1 ） 33 - 38 2018年08月

ISSN  1340-9379

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脳しんとうは、頭部への直接的な衝撃や頭部へ伝達する他の体の部位への衝撃で生じる頭部外傷である。脳しんとうの症状が完全に回復する前に運動を再開すると、脳しんとうを再発する危険性が高くなる。また、脳が発達途中である小児から青年期は、脳しんとうを起こしやすく、症状が完全に回復するまでに時間がかかり、脳しんとうを繰り返し起こすことで、致死的な病態や将来的な高次脳機能障害を引き起こす危険性が高くなる。以上のように、脳しんとうは学校において留意すべき頭部外傷であることから、脳しんとう後の学校における管理について、神奈川県内の2つの高等学校で検討した。フローチャートに則った脳しんとう後の対応を開始することで、教員および保健室での脳しんとうの発生状況、受傷した生徒等に関する正確な情報の収集ならびに共有が可能になった。2016年度に発生した36件の脳しんとうのうち、34件がコンタクトスポーツの部活動中の発生であった。受傷者31人のうち、過去5年以内に脳しんとうの既往がある生徒が7人(23%)おり、脳しんとうの再発の危険性が高いことが確認された。フローチャートに則った脳しんとう後の対応を通して、学校における脳しんとう発生予防の立案、脳しんとう後の生徒の慎重な健康管理が可能となった。このフローチャートに則った脳しんとう後の対応は、学校の安全配慮義務上、有用と考えられた。(著者抄録)

13年間における当大学での自動体外式除細動器の使用経験

清 奈帆美, 和井内 由充子, 山崎 花梨, 小原 慶子, 澁谷 麻由美, 松本 可愛, 齋藤 圭美, 當仲 香, 高橋 綾, 中園 春奈, 牧野 伸司, 広瀬 寛, 森 正明, 河邊 博史

CAMPUS HEALTH （(公社)全国大学保健管理協会）  55 （ 1 ） 195 - 197 2018年03月

ISSN  1341-4313

Temporal trends in renal function and birthweight in Japanese adolescent males (1998-2015)

Kanda T., Takeda A., Hirose H., Abe T., Urai H., Inokuchi M., Wakino S., Tokumura M., Itoh H., Kawabe H.

Nephrology Dialysis Transplantation （Nephrology Dialysis Transplantation）  33 （ 2 ） 304 - 310 2018年02月

ISSN  09310509

　概要を見る

© 2017 The Author . Published by Oxford University Press on behalf of ERA-EDTA. Background Low birthweight (LBW) is a worldwide public health problem, demonstrating an increasing incidence in developed countries, including Japan. LBW is also a risk factor for later development of chronic kidney disease (CKD). To date, studies have not evaluated the population impacts of increasing LBW rates on renal function. Methods Estimated glomerular filtration rate (EGFR) was evaluated in 3737 Japanese adolescent males (15-16 years old) using annual cross-sectional data over an 18-year period (1998-2015). Results Between the initial (1998-2003) and final (2010-15) periods of the study, the mean birthweight decreased from 3213.4 ± 383.8 to 3116.2 ± 382.3 g and the LBW rate increased from 2.5 to 5.5% (both P ≤ 0.01). Additionally, the mean EGFR decreased from 105.1 ± 15.9 to 97.4 ± 13.8 mL/min/1.73 m 2 and the prevalence of mildly reduced renal function (EGFR ≤ 60-<90 mL/min/1.73 m 2) increased from 16.4 to 30.0% (both P ≤ 0.01), most evident in the LBW group (from 10.3 to 41.7%, P ≤0.01). The prevalence of proteinuria also increased significantly. Mildly reduced renal function was significantly associated with LBW [odds ratio (LBW 3000-3999 g) 1.51; 95% confidence interval 1.00-2.55; P = 0.047]. Conclusions In this population of Japanese adolescents, the frequency of mildly reduced renal function increased as the LBW frequency increased. Our findings may have implications for the broader Japanese population as well as for other populations in which the prevalence of LBW is increasing.

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Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

Demenais F., Margaritte-Jeannin P., Barnes K., Cookson W., Altmüller J., Ang W., Barr R., Beaty T., Becker A., Beilby J., Bisgaard H., Bjornsdottir U., Bleecker E., Bønnelykke K., Boomsma D., Bouzigon E., Brightling C., Brossard M., Brusselle G., Burchard E., Burkart K., Bush A., Chan-Yeung M., Chung K., Couto Alves A., Curtin J., Custovic A., Daley D., De Jongste J., Del-Rio-Navarro B., Donohue K., Duijts L., Eng C., Eriksson J., Farrall M., Fedorova Y., Feenstra B., Ferreira M., Freidin M., Gajdos Z., Gauderman J., Gehring U., Geller F., Genuneit J., Gharib S., Gilliland F., Granell R., Graves P., Gudbjartsson D., Haahtela T., Heckbert S., Heederik D., Heinrich J., Heliövaara M., Henderson J., Himes B., Hirose H., Hirschhorn J., Hofman A., Holt P., Hottenga J., Hudson T., Hui J., Imboden M., Ivanov V., Jaddoe V., James A., Janson C., Jarvelin M., Jarvis D., Jones G., Jonsdottir I., Jousilahti P., Kabesch M., Kähönen M., Kantor D., Karunas A., Khusnutdinova E., Koppelman G., Kozyrskyj A., Kreiner E., Kubo M., Kumar R., Kumar A., Kuokkanen M., Lahousse L., Laitinen T., Laprise C., Lathrop M., Lau S., Lee Y., Lehtimäki T., Letort S., Levin A., Li G., Liang L., Loehr L., London S., Loth D., Manichaikul A.

Nature Genetics （Nature Genetics）  50 （ 1 ） 42 - 50 2018年01月

ISSN  10614036

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© 2017 The Author(s). We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

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Associations of Aging with Visceral Fat, HOMA-IR, and Beta-Cell Function in Humans

Hirose Hiroshi, Azuma Koichiro, Takayama Michiyo, Iwao Yasushi, Kawabe Hiroshi

DIABETES 66   A399 - A399 2017年06月

ISSN  0012-1797

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese

広瀬 寛

JOURNAL OF DIABETES RESEARCH 2017 2017年

研究論文（学術雑誌）,  ISSN  2314-6745

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Investigation of Metabolic Factors Associated with eGFR Decline Over 1 Year in a Japanese Population without CKD

Hayashi Kaori, Takayama Michiyo, Abe Takayuki, Kanda Takeshi, Hirose Hiroshi, Shimizu-Hirota Ryoko, Shiomi Eisuke, Iwao Yasushi, Itoh Hiroshi

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 24 （ 8 ） 863 - 875 2017年

ISSN  1340-3478

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EGFR IN JAPANESE MALE ADOLESCENT HAS DECREASED BETWEEN 1998 AND 2015, AND LOW BIRTH WEIGHT IS CORRELATED WITH RENAL FUNCTION

Kanda T., Takeda A., Hirose H., Urai H., Wakino S., Itoh H., Kawabe H.

NEPHROLOGY 21   80 - 80 2016年09月

ISSN  1320-5358

RELATIONSHIPS OF VISCERAL FAT AREA AND INSULIN RESISTANCE INDEX WITH BLOOD PRESSURE STATUS

Hirose Hiroshi, Takayama Michiyo, Shimizu-Hirota Ryoko, Iwao Yasushi, Kawabe Hiroshi

JOURNAL OF HYPERTENSION 34   E393 - E393 2016年09月

ISSN  0263-6352

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Serum High-Molecular-Weight Adiponectin Levels Correlate with Various Metabolic Parameters in Special Health Checkup Programs

Hirose Hiroshi, Azuma Koichiro, Shimizu-Hirota Ryoko, Taka-Yama Michiyo, Iwao Yasushi, Kawabe Hiroshi

DIABETES 65   A626 - A627 2016年06月

ISSN  0012-1797

Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies

Matsuba Ren, Imamura Minako, Tanaka Yasushi, Iwata Minoru, Hirose Hiroshi, Kaku Kohei, Maegawa Hiroshi, Watada Hirotaka, Tobe Kazuyuki, Kashiwagi Atsunori, Kawamori Ryuzo, Maeda Shiro

PLOS ONE 11 （ 4 ）  2016年04月

ISSN  1932-6203

　概要を見る

<p>Aim We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and six susceptibility loci (TMEM154, SSR1, FAF1, POU5F1, ARL15, and MPHOSPH9) originally identified by a transethnic meta-analysis of genomewide association studies (GWAS) in 2014. Methods We genotyped 7,620 Japanese participants (5,817 type 2 diabetes patients and 1,803 controls) for each of the single nucleotide polymorphisms (SNPs) using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using logistic regression analysis. Results Of the six SNPs examined in this study, four (rs6813195 near TMEM154, rs17106184 in FAF1, rs3130501 in POU5F1 and rs4275659 near MPHOSPH9) had the same direction of effect as in the original reports, but two (rs9505118 in SSR1 and rs702634 in ARL15) had the opposite direction of effect. Among these loci, rs3130501 and rs4275659 were nominally associated with type 2 diabetes (rs3130501; p = 0.017, odds ratio [OR] = 1.113, 95% confidence interval [CI] 1.019-1.215, rs4275659; p = 0.012, OR = 1.127, 95% CI 1.026-1.238, adjusted for sex, age and body mass index), but we did not observe a significant association with type 2 diabetes for any of the six evaluated SNP loci in our Japanese population. Conclusions Our results indicate that effects of the six SNP loci identified in the transethnic GWAS metaanalysis are not major among the Japanese, although SNPs in POU5F1 and MPHOSPH9 loci may have some effect on susceptibility to type 2 diabetes in this population.</p>

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Metabolic Factors in Addition to Aging and Current Smoking Are Independently Associated With the Prevalence of Colorectal Neoplasia in Japan: Analyses of Comprehensive Health Checkup Data

広瀬 寛

GASTROENTEROLOGY 150 （ 4 ） S767 - S768 2016年04月

研究論文（学術雑誌）,  ISSN  0016-5085

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Effects of Aging on Visceral and Subcutaneous Fat Areas and on Homeostasis Model Assessment of Insulin Resistance and Insulin Secretion Capacity in a Comprehensive Health Checkup

Hirose Hiroshi, Takayama Michiyo, Iwao Yasushi, Kawabe Hiroshi

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 23 （ 2 ） 207 - 215 2016年02月

ISSN  1340-3478

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<p>Aim:The association between aging and insulin resistance has been unclear. We evaluated the effects of aging on visceral fat area (VFA) and subcutaneous fat area (SFA) measured by computed tomography, homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) among participants in a comprehensive health checkup. Methods: This study included 1,050 male and 700 female Japanese participants aged 35-84 years in our comprehensive health checkup program during a 2-year period. Participants who were on medication for diabetes mellitus or those who met the pre-determined exclusion criteria were excluded. The participants were divided into five groups according to age. Results: As age increased from Group 1 to Group 5, both VFA and VFA/SFA ratio significantly increased in both male and female participants, whereas log[HOMA-IR] linearly and significantly decreased (p＜0.0001 for each). Body mass index (BMI), waist circumference (WC), and SFA increased with age in female participants but decreased in male participants. Although age was not or only weakly correlated with log[glucose] and log[HbA1c] in both male and female participants, age showed significant negative correlations with log[insulin], log[HOMA-IR], and log[HOMA-β] even after adjusting for BMI and WC (p＜0.0001 for each). Serum high-molecular-weight adiponectin (HMW-ADPN) levels were measured in 114 male and 87 female participants, and log[HMW-ADPN] was negatively correlated with log[HOMA-IR] and positively correlated with age in both male and female participants. Conclusions: In the present study, both male and female participants showed increases in VFA and VFA/SFA ratio and decreases in insulin, HOMA-IR, and HOMA-β with age.</p>

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