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Exploration of novel biomarkers to predict cognitive decline in people with diabetes and elucidation of the mechanisms

Research Project

Project/Area Number 19K07898
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionTokyo Medical University

Principal Investigator

Suzuki Ryo  東京医科大学, 医学部, 主任教授 (20396732)

Co-Investigator(Kenkyū-buntansha) 青山 倫久  東京大学, 医学部附属病院, 助教 (50645538)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords酸化型アルブミン / 糖尿病合併症 / 高齢1型糖尿病 / 酸化ストレス / 認知機能 / 糖尿病
Outline of Research at the Start

本研究は、参加同意の得られた糖尿病患者を対象に、①認知機能検査の結果と脳ステロール代謝や酸化ストレス等を反映する新規血液バイオマーカーの関連を評価し、②2年間の追跡によって観察される認知機能の変化および血管合併症の進行と関連する指標を探索し、③培養細胞や遺伝子操作マウス、糖尿病モデルマウスを用いて候補分子が認知機能に影響するメカニズムを解明する。

Outline of Final Research Achievements

We investigated 164 diabetic subjects to assess the correlation between oxidized albumin (non-mercaptalbumin, HNA%) and various clinical parameters. HNA% was significantly associated with the severity of multiple complications including neuropathy and nephropathy. No significant association was found between HNA% and MMSE score.
We classified 225 type 1 diabetes patients who were treated at a university hospital to assess the current state of aging and the factors associated with severe hypoglycemia (SH). Older patients accounted for 36% of all patients. In the patients who experienced SH, the serum C-peptide levels were lower than those without SH. Older patients indicated poor association between low blood glucose levels noted at regular visits and SH episodes.

Academic Significance and Societal Importance of the Research Achievements

当初の仮説である認知機能との関連は示せなかったが、酸化ストレスの血清バイオマーカーが、代表的な糖尿病合併症である神経障害、網膜症、腎症ならびに冠動脈疾患既往の全てと有意に相関したとする報告は初であり、特に腎機能低下に至っていない患者群でも、神経障害がある場合に有意に高値であったことから、酸化型アルブミンは糖尿病合併症の進行を早期に予測する有用なマーカーとなる可能性がある。
インスリン治療を必須とする1型糖尿病は重症低血糖の回避が容易でない。高齢1型糖尿病を対象とした臨床研究は少なく、重症低血糖リスクが高い群の抽出が困難であることを示した。1型糖尿病の高齢化への対応は急を要し、更なる検討を要する。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2021 2020 2019

All Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 13 results,  Open Access: 10 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results)

  • [Journal Article] Factors Associated With Treatment Adherence and Satisfaction in Type 2 Diabetes Management in Japan: Results From a Web-Based Questionnaire Survey2021

    • Author(s)
      Suzuki Ryo、Saita Shun、Nishigaki Nobuhiro、Kisanuki Koichi、Shimasaki Yukio、Mineyama Tomoka、Odawara Masato
    • Journal Title

      Diabetes Therapy

      Volume: 12 Issue: 9 Pages: 2343-2358

    • DOI

      10.1007/s13300-021-01100-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Real-World, Prospective, Non-interventional Study of Adults with T2D Switching to IDegAsp from Glargine U100 or U300 in Japan2021

    • Author(s)
      Shigiyama Fumika、Liu Lei、Nordahl Helene、Suzuki Ryo、Yamamoto Yuiko、Hirose Takahisa
    • Journal Title

      Diabetes Therapy

      Volume: 12 Issue: 9 Pages: 2405-2421

    • DOI

      10.1007/s13300-021-01117-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association between glycemic control and cardiovascular events in older Japanese adults with diabetes mellitus: An analysis of the Japanese medical administrative database2021

    • Author(s)
      Yokote Koutaro、Suzuki Ryo、Gouda Maki、Iijima Hiroaki、Yamazaki Akiko、Inagaki Masaya
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 12 Issue: 11 Pages: 2036-2045

    • DOI

      10.1111/jdi.13575

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between diabetes duration and self-stigma development in Japanese people with type 2 diabetes: A secondary analysis of cross-sectional data2021

    • Author(s)
      Kato Asuka、Fujimaki Yuko、Fujimori Shin、Isogawa Akihiro、Onishi Yukiko、Suzuki Ryo、Ueki Kohjiro、Yamauchi Toshimasa、Kadowaki Takashi、Hashimoto Hideki
    • Journal Title

      BMJ Open

      Volume: 11 Issue: 12 Pages: e055013-e055013

    • DOI

      10.1136/bmjopen-2021-055013

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A cross-sectional study of the correlation between diabetic therapy and serum zinc concentrations2021

    • Author(s)
      Sakurai Mamoru、Sasaki Junko、Suwanai Hirotsugu、Shikuma Jumpei、Ito Rokuro、Odawara Masato、Miwa Takashi、Suzuki Ryo
    • Journal Title

      Diabetology International

      Volume: 13 Issue: 1 Pages: 177-187

    • DOI

      10.1007/s13340-021-00521-6

    • NAID

      40022802936

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] How self-stigma affects patient activation in persons with type 2 diabetes: A cross-sectional study2020

    • Author(s)
      Kato A, Fujimaki Y, Fujimori S, Isogawa A, Onishi Y, Suzuki R, Ueki K, Yamauchi T, Kadowaki T, Hashimoto H
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 5 Pages: e034757-e034757

    • DOI

      10.1136/bmjopen-2019-034757

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Understanding the experiences of long-term maintenance of self-worth in persons with type 2 diabetes in Japan: a qualitative study.2020

    • Author(s)
      Kato A, Yoshiuchi K, Fujimaki Y, Fujimori S, Kobayashi Y, Yamada T, Kobayashi M, Izumida Y, Suzuki R, Yamauchi T, Kadowaki T.
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 8 Pages: e034758-e034758

    • DOI

      10.1136/bmjopen-2019-034758

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Factors Associated with Callus Formation in the Plantar Region through Gait Measurement in Patients with Diabetic Neuropathy: An Observational Case-Control Study2020

    • Author(s)
      Amemiya Ayumi、Noguchi Hiroshi、Oe Makoto、Takehara Kimie、Ohashi Yumiko、Suzuki Ryo、Yamauchi Toshimasa、Kadowaki Takashi、Sanada Hiromi、Mori Taketoshi
    • Journal Title

      Sensors

      Volume: 20 Issue: 17 Pages: 4863-4863

    • DOI

      10.3390/s20174863

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin- and Lipopolysaccharide-Mediated Signaling in Adipose Tissue Macrophages Regulates Postprandial Glycemia through Akt-mTOR Activation2020

    • Author(s)
      Toda G、Soeda K、Okazaki Y、Kobayashi N、Masuda Y、Arakawa N、Suwanai H、Masamoto Y、Izumida Y、Kamei N、Sasako T、Suzuki R、Kubota T、Kubota N、Kurokawa M、Tobe K、Noda T、Honda K、Accili D、Yamauchi T、Kadowaki T、Ueki K
    • Journal Title

      Molecular Cell

      Volume: 79 Issue: 1 Pages: 1-2

    • DOI

      10.1016/j.molcel.2020.04.033

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidized albumin in blood reflects the severity of multiple vascular complications in diabetes mellitus.2020

    • Author(s)
      Kobayashi Y, Suzuki R, Yasukawa K, Oba K, Yamauchi T, Yatomi Y, Kadowaki T
    • Journal Title

      Metab Open

      Volume: 6 Pages: 100032-100032

    • DOI

      10.1016/j.metop.2020.100032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein kinase C promotes choline transporter like protein 1 function via improved cell surface expression in immortalized human hepatic cells.2020

    • Author(s)
      Ishikawa T, Suwanai H, Shikuma J, Suzuki R, Yamanaka T, Odawara M, Inazu M
    • Journal Title

      Mol Med Rep

      Volume: 21 Pages: 777-785

    • DOI

      10.3892/mmr.2019.10894

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessing hypoglycemia frequency using flash glucose monitoring in older Japanese patients with type 2 diabetes receiving oral hypoglycemic agents.2019

    • Author(s)
      Abe H, Shikuma J, Suwanai H, Sano K, Okumura T, Kan K, Takahashi T, Miwa T, Suzuki R, Odawara M
    • Journal Title

      Geriatr Gerontol Int

      Volume: 19 Issue: 10 Pages: 1030-1035

    • DOI

      10.1111/ggi.13765

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Classification of Clinically Diagnosed Alzheimer's Disease Associated with Diabetes Based on Amyloid and Tau PET Results.2019

    • Author(s)
      Takenoshita N, Shimizu S, Kanetaka H, Sakurai H, Suzuki R, Miwa T, Odawara M, Ishii K, Shimada H, Higuchi M, Suhara T, Hanyu H
    • Journal Title

      J Alzheimers Dis.

      Volume: 71 Issue: 1 Pages: 261-271

    • DOI

      10.3233/jad-190620

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Is strict glycaemic control meaningless for the elderly?: No2019

    • Author(s)
      Ryo Suzuki
    • Organizer
      International Diabetes Federation Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 糖尿病診療で優先的に認知症スクリーニング検査を考慮すべきハイリスク群の探索2019

    • Author(s)
      小林由佳、鈴木亮、門脇孝、山内敏正
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] フレイルを考慮した高齢者糖尿病の治療2019

    • Author(s)
      鈴木亮
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 高齢者糖尿病の認知機能低下予防2019

    • Author(s)
      鈴木亮
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 高齢者糖尿病の認知機能障害2019

    • Author(s)
      鈴木亮
    • Organizer
      第73回日本栄養・食糧学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 高齢者糖尿病の課題 フレイル/認知症2019

    • Author(s)
      鈴木亮
    • Organizer
      第34回日本糖尿病合併症学会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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