Updated on 2025/03/27

写真a

 
Hadate Toshimi
 
Organization
University Hospital Assistant Professor
Title
Assistant Professor
Contact information
メールアドレス
External link

Degree

  • Doctor of Medicine ( 2023.9   Ehime University )

Research Interests

  • 疫学

  • 遺伝学

  • レジスチン

  • 糖尿病内科学

  • 喫煙

Research Areas

  • Life Science / Genome biology

  • Life Science / Genetics

  • Life Science / Metabolism and endocrinology

Research Subject

  • Serum resistin was increased in current smokers with the G-A haplotype defined by SNP-420 and SNP-358 in the Japanese cohort: The Toon Genome Study

Education

  • 愛媛大学大学院   医学系研究科   糖尿病内科学

    2017.10 - 2023.9

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  • Ehime University   School of Medicine

    2004.4 - 2010.3

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Research History

  • 愛媛大学医学部附属病院   検査部（糖尿病内科・臨床検査医学）   助教

    2020.8

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  • 愛媛大学医学部附属病院   糖尿病内科   上級医員

    2016.4 - 2020.7

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  • 松山赤十字病院   内科   医師

    2014.4 - 2016.3

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  • 愛媛大学医学部附属病院   糖尿病内科   医員

    2012.4 - 2014.3

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  • 愛媛大学医学部附属病院   総合臨床研修センタ―   研修医

    2010.4 - 2012.3

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Professional Memberships

Qualification acquired

  • 日本内科学会総合内科専門医

  • 日本糖尿病学会糖尿病内科専門医

  • 日本内科学会認定内科医

  • 医師免許証

Papers

  • Genetic variation in the RETN promoter, accompanied by latent sarcopenic obesity, led to insulin resistance in a Japanese cohort: the Toon Genome Study. International journal

    Yosuke Ikeda, Ryoichi Kawamura, Yasuharu Tabara, Koutatsu Maruyama, Daisuke Shiokawa, Misaki Takakado, Toshimi Hadate, Yasunori Takata, Jun Ohashi, Isao Saito, Yoshihiro Ogawa, Haruhiko Osawa

    Diabetologia   2024.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    AIMS/HYPOTHESIS: Resistin, inducing insulin resistance, is elevated in the sera of individuals with the G-A haplotype at c.-420 C>G (rs1862513) and c.-358 G>A (rs3219175). This haplotype is associated with visceral obesity and low grip strength. To elucidate the hidden relationship between the G-A haplotype and insulin resistance, integration of specific phenotypes defined by body composition and 75 g OGTT would be a promising strategy. METHODS: The 803 Japanese participants (average age: 62 years), attending annual medical checkups, were evaluated every 5 years. Participants were categorised by skeletal muscle mass, visceral fat score and OGTT results. Hierarchical clustering was performed using body composition and glucose metabolism parameters. Whole blood cells from participants homozygous for the G-A or C-G haplotype (n=25 and 33, respectively), matched for age, sex and BMI, using propensity score matching, were used for RNA-seq, pathway analysis and RT-PCR. RESULTS: Multivariate analysis showed that individuals with the G-A haplotype, when accompanied by latent skeletal muscle loss and visceral obesity (latent sarcopenic obesity), presented a pronounced deterioration in insulin resistance over a 5 year period. Cluster 2, identified using hierarchical clustering, was characterised by low skeletal muscle mass, visceral obesity and insulin resistance. This cluster, with the G-A haplotype, demonstrated deterioration in insulin resistance. RNA-seq and RT-PCR revealed altered expression of mitophagy-related genes in whole blood cells of the G-A homozygotes. CONCLUSIONS/INTERPRETATION: The G-A haplotype, accompanied by latent low skeletal muscle mass and visceral obesity, led to the deterioration of insulin resistance over a 5 year period in this cohort, possibly through the altered expression of mitophagy-related genes.

    DOI： 10.1007/s00125-024-06322-1

    PubMed

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  • Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study. International journal

    Toshimi Hadate, Ryoichi Kawamura, Yasuharu Tabara, Koutatsu Maruyama, Misaki Takakado, Yosuke Ikeda, Jun Ohashi, Yasunori Takata, Isao Saito, Haruhiko Osawa

    Journal of human genetics   68 ( 11 )   745 - 750   2023.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.

    DOI： 10.1038/s10038-023-01176-8

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  • Resistin G-A haplotype at SNP-420/-358 is associated with the latent sarcopenic obesity index in the toon genome study.

    Yosuke Ikeda, Ryoichi Kawamura, Yasunori Takata, Yasuharu Tabara, Koutatsu Maruyama, Misaki Takakado, Toshimi Hadate, Jun Ohashi, Isao Saito, Yoshihiro Ogawa, Haruhiko Osawa

    Journal of diabetes investigation   14 ( 5 )   686 - 694   2023.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    AIM/INTRODUCTION: Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G-A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and - 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage. MATERIALS AND METHODS: We cross-sectionally analyzed 567 community-dwelling Japanese participants attending annual medical check-ups in which the sarcopenic obesity index was evaluated. The age- and gender-matched normal glucose tolerance subjects with G-A homozygotes and those with C-G homozygotes were examined via RNA-sequencing and pathway analysis (each n = 3), and RT-PCR (each n = 8). RESULTS: In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G-A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm2 and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G-A homozygotes compared with C-G homozygotes. RT-PCR revealed that TNF mRNA was higher in G-A homozygotes than in C-G homozygotes. CONCLUSIONS: The G-A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF-α.

    DOI： 10.1111/jdi.13998

    PubMed

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  • 一般住民においてレジスチンSNP-420G/-358Aハプロタイプはダイナペニア肥満に類似したクラスターと関連する

    池田 陽介, 川村 良一, 田原 康玄, 丸山 広達, 高門 美沙季, 羽立 登志美, 高田 康徳, 斉藤 功, 大澤 春彦

    糖尿病   66 ( Suppl.1 )   S - 244   2023.4

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    Language：Japanese   Publisher：(一社)日本糖尿病学会  

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  • 正常型の一般住民においてレジスチンSNPは炎症を伴う腹部肥満及びインスリン抵抗性と関連する【東温ゲノムスタディ】

    川村 良一, 田原 康玄, 丸山 広達, 高門 美沙季, 池田 陽介, 羽立 登志美, 斉藤 功, 高田 康徳, 大澤 春彦

    糖尿病   66 ( Suppl.1 )   S - 172   2023.4

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    Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Books

  • 臨床検査6 典型例の臨床検査を学ぶ 2型糖尿病 p656－660. 医学書院 2021.

    2021 

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  • 糖尿病の診断と成因. OCULISTA 眼科医のための糖尿病トータルガイドMB OCULI. No.68: 10-18, 2018.

    2018 

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MISC

  • CGMで褐色細胞腫摘出術前後の血糖推移を観察し得た緩徐進行1型糖尿病の1例

    奥村 力, 松下 由美, 高門 美沙季, 羽立 登志美, 川村 良一, 高田 康徳, 小山 花南江, 雑賀 隆史, 大澤 春彦

    糖尿病   61 ( 5 )   343 - 343   2018.5

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    Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Presentations

  • 正常型の一般住民においてレジスチンSNPは炎症を伴う腹部肥満及びインスリン抵抗性と関連する【東温ゲノムスタディ】

    川村 良一, 田原 康玄, 丸山 広達, 高門 美沙季, 池田 陽介, 羽立 登志美, 斉藤 功, 高田 康徳, 大澤 春彦

    糖尿病  2023.4  (一社)日本糖尿病学会

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    Event date： 2023.4

    Language：Japanese  

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  • SNP-420 C/Gにおいて,Cのメチル化低値と喫煙は,血中レジスチン高値と関連する【東温ゲノムスタディ】

    羽立 登志美, 川村 良一, 田原 康玄, 丸山 広達, 高門 美沙季, 池田 陽介, 斉藤 功, 高田 康徳, 大澤 春彦

    糖尿病  2023.4  (一社)日本糖尿病学会

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    Event date： 2023.4

    Language：Japanese  

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  • 一般住民においてレジスチンSNP-420G/-358Aハプロタイプはダイナペニア肥満に類似したクラスターと関連する

    池田 陽介, 川村 良一, 田原 康玄, 丸山 広達, 高門 美沙季, 羽立 登志美, 高田 康徳, 斉藤 功, 大澤 春彦

    糖尿病  2023.4  (一社)日本糖尿病学会

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    Event date： 2023.4

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  • レジスチンSNP-420/-358ハプロタイプと白血球数は相互に血中レジスチン高値と関連する

    川村 良一, 田原 康玄, 高田 康徳, 丸山 広達, 高門 美沙季, 池田 陽介, 羽立 登志美, 斉藤 功, 大澤 春彦

    糖尿病  2022.11  (一社)日本糖尿病学会

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    Event date： 2022.11

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  • レジスチンSNP-420/-358ハプロタイプと喫煙は相互に血中レジスチンを高める

    羽立 登志美, 川村 良一, 高田 康徳, 田原 康玄, 丸山 広達, 高門 美沙季, 池田 陽介, 斉藤 功, 大澤 春彦

    糖尿病  2022.11  (一社)日本糖尿病学会

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    Event date： 2022.11

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Awards

  • 大学院医学専攻中間審査会 優秀研究賞

    2021.3   愛媛大学大学院医学系研究科  

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  • Young Investigator’s Award (YIA)

    2017.11   日本糖尿病学会中国四国地方会第55回総会  

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Teaching Experience

  • 糖尿病学（臨床検査医学各論）

    2021.7 Institution：愛媛大学医学部医学科第３学年

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  • 医科学研究Ⅱ

    2021.4 Institution：愛媛大学医学部医学科第２学年

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  • 医科学研究Ⅰ

    2018.4 Institution：愛媛大学医学部医学科第１学年

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  • 糖尿病

    2017 Institution：愛媛医療センター附属看護学校

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