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Does microangiopathy due to advanced glycation end products play a role in the development of osteomyelitis in diabetic foot ulcers?

Research Project

Project/Area Number 20K09863
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionJuntendo University (2021-2023)
Kobe University (2020)

Principal Investigator

Fujii Miki  順天堂大学, 大学院医学研究科, 准教授 (80444602)

Co-Investigator(Kenkyū-buntansha) 榊原 俊介  神戸大学, 医学研究科, 客員准教授 (50444592)
寺師 浩人  神戸大学, 医学部附属病院, 教授 (80217421)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病性足潰瘍 / 骨髄炎 / AGE / 腱 / 終末糖化産物
Outline of Research at the Start

糖尿病患者と非糖尿病患者の足趾において、腱組織内でのAGEの局在と、骨への細菌の感染経路を確認する事で糖尿病性足潰瘍の骨髄炎の発症経路を解明する。

Outline of Final Research Achievements

We retrospectively performed an immunohistochemical examination of 64 tendons from toes of 64 patients (50 males, 14 females, aged 69.7±11.1 years, 48 patients with diabetes) who underwent toe resection due to foot ulcers. Significant AGE stains were identified in vascular endothelial cells. The degree of AGE accumulation in vascular endothelial cells was classified into 4 stages: 0 (negative stain), +1 (weak or partially positive), +2 (clear or whole perimeter positive), and +3 (strong and thick positive). The findings were (diabetes vs non-diabetes): 9 (18.8%) vs 2 (12.5%) in stage 0, 20 (41.7%) vs 10 (62.5%) in stage 1, 16 (33.3%) vs 4 (25%) in stage 2, and 3 (62.5%) vs 0 in stage 3. AGE positivity rates (stages +1, +2, +3) of the patients <69 years with diabetes (n=21) was 80.7%, and those of patients without diabetes (n=2) was 66.7% (p=0.52).Our study indicates that tendon fragility may be caused by microangiopathy due to AGE accumulation in the vascular endothelial cells.

Academic Significance and Societal Importance of the Research Achievements

近年、生活習慣の変化に伴い日本でも糖尿病患者は増加し、それに伴い糖尿病性足潰瘍を発症する患者も増加している。糖尿病性足潰瘍が骨髄炎を合併すると切断になる危険性は非常に高くなり、患者のADLの低下だけでなく医療経済的にも大きな問題となる。骨髄炎発症のメカニズムが解明されれば、骨髄炎を予防する方法の解明やより効果的な抗生剤の投与方法に繋がる可能性があり社会的意義は大きい。AGEによる腱の栄養血管の微小血管障害が骨髄炎発症の一要因であることが判明すれば、AGE形成阻害薬が骨髄炎の新たな治療薬となる可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (38 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (28 results) (of which Int'l Joint Research: 10 results,  Invited: 10 results) Book (5 results)

  • [Journal Article] The degree of blood supply and infection control needed to treat diabetic critical limb ischemia with forefoot osteomyelitis.2021

    • Author(s)
      Fujii M, Terashi H, Yokono K. Armstrong DG.
    • Journal Title

      J Am Podiatr Med Assoc

      Volume: 111 Pages: 1-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive factors for limb salvage and foot ulcer recurrence in patients with chronic limb-threatening ischemia after multidisciplinary team treatment: a six year Japanese single-center study.2021

    • Author(s)
      Fujii M, Yamada A, Yamawaki K, Tsuda S, Miyamoto N, Gan K, Terashi H.
    • Journal Title

      Int J Low Extrem Wounds

      Volume: Sep Pages: 0-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immediate effects of weight-bearing calf stretching on ankle dorsiflexion range of motion and plantar pressure during gait in patients with diabetes mellitus.2021

    • Author(s)
      Maeshige N, Uemura M, Hirasawa Y, Yoshikawa Y, Moriguchi M, Kawabe N, Fujii M, Terashi H, Fujino H.
    • Journal Title

      Int J Low Extrem Wounds

      Volume: July Pages: 0-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in Skin Perfusion Pressure After Endovascular Treatment for Chronic Limb-Threatening Ischemia.2021

    • Author(s)
      Ichihashi S, Takahara M, Fujimura N, Shibata T, Fujii M, Kato T, Tsubakimoto Y, Iwakoshi S, Obayashi K, Kichikawa K.
    • Journal Title

      J Endovasc Ther

      Volume: 28 Pages: 208-214

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 踵部褥瘡を識(し)る.2021

    • Author(s)
      藤井美樹
    • Journal Title

      日本褥瘡学会誌

      Volume: 23 Pages: 26-31

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 糖尿病性足潰瘍の感染をどう克服するか?2023

    • Author(s)
      藤井美樹 田中里佳 水野博司 寺師浩人
    • Organizer
      第66回日本形成外科学会総会・学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 感染創をどう治療するのか2023

    • Author(s)
      藤井美樹
    • Organizer
      2023JET
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 糖尿病性足潰瘍の感染拡大に終末糖化産物による微小血管障害が関与するか2023

    • Author(s)
      藤井美樹 田中里佳 水野博司 寺師浩人
    • Organizer
      第32回日本形成外科学会基礎学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 感染を伴った創部管理について2023

    • Author(s)
      藤井美樹
    • Organizer
      第36回日本外科感染症学会総会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 糖尿病性足潰瘍の感染拡大に終末糖化産物による微小血管障害が関与するか2022

    • Author(s)
      藤井美樹
    • Organizer
      第52回日本創傷治癒学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 糖尿病性足潰瘍の感染拡大に終末糖化産物による微小血管障害が関与するか2022

    • Author(s)
      藤井美樹
    • Organizer
      第31回日本形成外科学会基礎学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Novel therapeutic apheresis ‘Rheocarna’ for the no-option patients with chronic limb-threatening ischemia. Free papers& Awards.2021

    • Author(s)
      Fujii M, Tanaka R and Mizuno H.
    • Organizer
      DFcon2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Session2: D-foot international. Diabetic foot ulcer debridement and local flaps.2021

    • Author(s)
      Fujii M.
    • Organizer
      7th Annual Conference of IADFS
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Session8: IADFS PROGRAMME: CASE DISCUSSIONS AND TAKE HOME MESSAGE. Conservative Treatment Cases2021

    • Author(s)
      Fujii M.
    • Organizer
      7th Annual Conference of IADFS,
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] MRI-FOOT MASTERCLASS.2021

    • Author(s)
      Fujii M.
    • Organizer
      The Diabetic foot society of India annual conference2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Predictive factors for limb salvage and foot ulcer recurrence in patients with chronic limb-threatening ischemia after a multidisciplinary team treatment: a 6-year Japanese single-center study.2021

    • Author(s)
      Fujii M.
    • Organizer
      Diabetic Limb Salvage Conference 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] CLINICAL EXPERIENCE WITH COLLATEGENE FOR THE MANAGEMENT OF CHRONIC LIMB-THREATENING ISCHEMIA2021

    • Author(s)
      Fujii M, Tanaka R and Mizuno H.
    • Organizer
      Plastic Surgery The Meeting 2021,
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糖尿病性足潰瘍の骨髄炎は骨端の血管孔への細菌感染から生じる2021

    • Author(s)
      藤井美樹、田中里佳、水野博司、寺師浩人
    • Organizer
      第51回日本創傷治癒学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病性足潰瘍の感染拡大に終末糖化産物による微小血管障害が関与するか2021

    • Author(s)
      藤井美樹、田中里佳、水野博司、寺師浩人
    • Organizer
      第30回日本形成外科学会基礎学術集会,
    • Related Report
      2021 Research-status Report
  • [Presentation] Multidisciplinaryteamtreatmentforthepatientswithchroniclimbthreate ningischemia.2021

    • Author(s)
      Fujii M, Hayashi T, Yamashiro K, Terashi H
    • Organizer
      第64回日本形成外科学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 第2章 足病発症から完治まで2021

    • Author(s)
      藤井美樹
    • Organizer
      第2回日本フットケア・足病医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 糖尿病性足潰瘍の感染拡大に終末糖化産物による微小血管障害が関与するか2021

    • Author(s)
      藤井美樹 林 知子 山城憲二郎 寺師浩人
    • Organizer
      第64回日本形成外科学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] エビデンスに基づく下肢救済治療2021

    • Author(s)
      藤井美樹 林 知子 山城憲二郎 寺師浩人
    • Organizer
      第13回日本創傷外科学会総会・学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 病院と在宅の創傷治療-その違いと使い分け-2021

    • Author(s)
      藤井美樹
    • Organizer
      第2回日本フットケア・足病医学会年次学術集会,
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 脱細胞化組織「OASIS」~創傷治療における新たな選択肢としての可能性について考える~2021

    • Author(s)
      藤井美樹
    • Organizer
      第13回日本創傷外科学会総会・学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 創傷管理の新時代を切り拓く超音波デブリードマン機器 国内初の’超音波デブリードマン装置’見参!2021

    • Author(s)
      藤井美樹
    • Organizer
      第13回日本創傷外科学会総会・学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 透析患者の足病に対する集学的治療2021

    • Author(s)
      藤井美樹
    • Organizer
      第11回中四国臨床工学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] DIABETIC FOOT OSTEOMYELITIS IS CAUSEDBY BACTERIAL INVASION THROUGH THE NUTRIENT FORAMEN IN THE EPIPHYSIS2020

    • Author(s)
      Fujii M, Terashi H
    • Organizer
      第63回日本形成外科学会・学術集会(名古屋)
    • Related Report
      2020 Research-status Report
  • [Presentation] Diabetic Foot Osteomyelitis is Caused by Bacterial Invasion through the Nutrient Foramen in the Epiphysis2020

    • Author(s)
      Fujii M, Terashi H
    • Organizer
      THE Diabetic Foot Study Group 2020 VIRTUAL MEETING(web)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diabetic Foot Osteomyelitis is Caused by Bacterial Invasion through the Nutrient Foramen in the Epiphysis2020

    • Author(s)
      Fujii M, Terashi H
    • Organizer
      DFcon2020(web)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Diabetic Foot Osteomyelitis is Caused by Bacterial Invasion through the Nutrient Foramen in the Epiphysis2020

    • Author(s)
      Fujii M, Terashi H
    • Organizer
      Virtual Plastic Surgery The Meeting 2020(web)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 糖尿病性足潰瘍の骨髄炎は骨端の血管孔への細菌感染から生じる2020

    • Author(s)
      藤井美樹 寺師浩人
    • Organizer
      第29回日本形成外科学会基礎学術集会(横浜)
    • Related Report
      2020 Research-status Report
  • [Presentation] DIABETIC FOOT OSTEOMYELITIS IS CAUSED BY BACTERIAL INVASION THROUGH THE NUTRIENT FORAMEN IN THE EPIPHYSIS2020

    • Author(s)
      Fujii M, Terashi H
    • Organizer
      EWMA2020(web)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Book] 臨床整形外科2021

    • Author(s)
      藤井美樹、田中里佳
    • Publisher
      医学書院
    • Related Report
      2021 Research-status Report
  • [Book] WOC Nursing2021

    • Author(s)
      藤井美樹、寺師浩人
    • Publisher
      医学出版
    • Related Report
      2021 Research-status Report
  • [Book] 形成外科診療ガイドライン32021

    • Author(s)
      藤井美樹、寺師浩人
    • Publisher
      金原出版株式会社
    • Related Report
      2021 Research-status Report
  • [Book] 診療指針2021

    • Author(s)
      藤井美樹、寺師浩人
    • Publisher
      総合医学社
    • Related Report
      2021 Research-status Report
  • [Book] 第1特集「連携」が支えるフットケア 多職種・病診・地域連携における看護師の役割2021

    • Author(s)
      藤井美樹
    • Publisher
      メヂカルフレンド社
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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