Construction and application of a prediction model for the development of diabetic complications based on the effects of accumulation and variation of blood glucose, blood pressure, and lipids.
Project/Area Number |
19K07166
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Kumamoto University |
Principal Investigator |
Oniki Kentaro 熊本大学, 大学院生命科学研究部(薬), 准教授 (00613407)
|
Co-Investigator(Kenkyū-buntansha) |
猿渡 淳二 熊本大学, 大学院生命科学研究部(薬), 教授 (30543409)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | メタボリックメモリー / modeling / simulation / HbA1c / 糖尿病性腎臓病 / 微量アルブミン尿 / 糖尿病 / アルデヒド / 非線形近藤効果モデル / モデリング / 遺伝子 / モデリング&シミュレーション |
Outline of Research at the Start |
血糖・血圧・脂質の異常は“メタボリックメモリー”として身体に記憶され、糖尿病合併症の発症に関わる。本研究は、未だその実態が不明なメタボリックメモリーに着目し、糖尿病患者の健康寿命の延長と新規治療ターゲットの同定を目指した臨床研究である。具体的には、糖尿病患者、冠動脈疾患患者、人間ドック受診者の長期観察データを基に、モデリング&シミュレーションを基盤とした手法により、メタボリックメモリーを定量化し、糖尿病合併症の発症・治療薬の薬効を予測する統計学的モデルを構築する。その結果を基に、個々に効果的な治療の提案・支援を行うための汎用性の高い医療システムの開発と、新規治療ターゲットの創出を目指す。
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Outline of Final Research Achievements |
In this study, we examined the factors involved in the development of diabetic complications from the perspective of metabolic memory and obtained the following findings. 1). By expressing persistent hyperglycemia as the area under the HbA1c curve and clarifying that its increase is related to renal function decline, we showed the importance of the degree and duration of hyperglycemia exposed in type 2 diabetes patients.2). We newly devised "area under the HbA1c-time curve (HbA1c-AUC)" as an index of HbA1c variability and showed that HbA1c-AUC is related to the development of microalbuminuria in type 2 diabetes patients independently of mean HbA1c values. In addition, serum albumin oxidation level was higher in patients with higher HbA1c variability, suggesting that oxidative stress status is involved the association between HbA1c variability and microalbuminuria.
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Academic Significance and Societal Importance of the Research Achievements |
本検討では、血糖値の築盛効果と変動効果の両方について検討し、メタボリックメモリーの定量的評価を腎機能低下との関連性の観点から証明した。本研究結果から、曝露された高血糖の程度や期間並びに変動の重要性が示され、合併症発症・進行における詳細な病態生理機序の解明や、合併症予防のための個別化治療目標の設定等に繋がることが期待される。また、HbA1cの変動については、生活習慣の乱れやアドヒアランス不良、HbA1cの季節変動、治療薬の変更に起因すると考えられる。今後、変動が大きい患者に積極的介入を行うことで、糖尿病性腎臓病発症予防につながることが期待される。
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Additive Effects of Drinking Habits and a Susceptible Genetic Polymorphism on Cholesterol Efflux Capacity2023
Author(s)
Matsumoto E, Oniki K, Ota-Kontani A, Seguchi Y, Sakamoto Y, Kaneko T, Imafuku T, Maeda H, Watanabe H, Maruyama T, Ogata Y, Yoshida M, Harada-Shiba M, Saruwatari J, Ogura M.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 30
Issue: 1
Pages: 23-38
DOI
ISSN
1340-3478, 1880-3873
Year and Date
2023-01-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Predictive Ability of Visit-to-Visit Variability of HbA1c Measurements for the Development of Diabetic Kidney Disease: A Retrospective Longitudinal Observational Study2022
Author(s)
Yan Y, Kondo N, Oniki K, Watanabe H, Imafuku T, Sakamoto Y, Shigaki T, Maruyama A, Nakazawa H, Kaneko T, Morita A, Yoshida A, Maeda H, Maruyama T, Jinnouchi H, Saruwatari J.
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Journal Title
Journal of Diabetes Research
Volume: 2022
Pages: 6934188-6934188
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers2022
Author(s)
Yamashita T, Arima Y, Hoshiyama T, Tabata N, Sueta D, Kawahara Y, Ito M, Kanazawa H, Ishii M, Yamanaga K, Hanatani S, Takashio S, Araki S, Suzuki S, Yamamoto E, Kaikita K, Oniki K, Saruwatari J, Matsushita K, Tsujita K.
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Journal Title
JACC: Asia
Volume: 2
Issue: 1
Pages: 62-70
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences2022
Author(s)
Ishida T, Arima Y, Mizuno Y, Harada E, Yamashita T, Sueta D, Sakamoto K, Suzuki S, Kaikita K, Yamada Y, Shimomura H, Oniki K, Saruwatari J, Hokimoto S, Yasue H, Tsujita K.
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Journal Title
Heart and Vessels
Volume: 37
Issue: 2
Pages: 184-193
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison between the Effects of Loxoprofen and Acetaminophen on Postoperative Pain Following Radical Prostatectomy: A Propensity Score Matching Analysis2021
Author(s)
Nishimura F, Ushijima T, Nojima M, Hamada S, Hara K, Hamada Y, Kadowaki D, Miyamura S, Oniki K, Saruwatari J.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 44
Issue: 10
Pages: 1427-1432
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2021-10-01
Related Report
Peer Reviewed
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[Journal Article] Clusterin and Related Scoring Index as Potential Early Predictors of Response to Sorafenib in Hepatocellular Carcinoma2021
Author(s)
Narahara S, Watanabe T, Nagaoka K, Fujimoto N, Furuta Y, Tanaka K, Tokunaga T, Kawasaki T, Yoshimaru Y, Setoyama H, Oniki K, Saruwatari J, Tateyama M, Naoe H, Tanaka M, Tanaka Y, Sasaki Y.
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Journal Title
Hepatology Communications
Volume: -
Issue: 5
Pages: 1198-1212
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical profiles of Asians with NAFLD: A systematic review and meta-analysis2021
Author(s)
Kam L, Huang DQ, Teng MLP, Takahashi H, Tanaka K, Yasuda S, Fung J, Lee TY, Hyogo H, Ono M, Saruwatari J, Oniki K, Yeo YH, Barnett S, Henry L, Li J, Zou B, Cheung RC, Kumada T, Yuen MF, Eguchi Y, Toyoda H, Nguyen MH.
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Journal Title
Digestive Diseases(Basel, Switzerland)
Volume: -
Issue: 6
Pages: 734-744
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cysteinylated albumin as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes2021
Author(s)
Imafuku T, Watanabe H, Oniki K, Yoshida A, Kato H, Nakano T, Tokumaru K, Fujita I, Arimura N, Maeda H, Sakamoto Y, Kondo N, Morita A, Saruwatari J, Tanaka M, Matsushita K, Wada T, Fukagawa M, Otagiri M, Fitzgerald ML, Jinnouchi H, Maruyama T.
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Journal Title
Diabetes Care
Volume: 26
Issue: 6
Pages: e115-e117
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The epidemiology of NAFLD and lean NAFLD in Japan: a meta-analysis with individual and forecasting analysis, 1995-2040.2021
Author(s)
Ito T, Ishigami M, Zou B, Tanaka T, Takahashi H, Kurosaki M, Maeda M, Thin KN, Tanaka K, Takahashi Y, Itoh Y, Oniki K, Seko Y, Saruwatari J, Kawanaka M, Atsukawa M, Hyogo H, Ono M, Ogawa E, Barnett SD, Stave CD, Cheung RC, Fujishiro M, Eguchi Y, Toyoda H, Nguyen MH.
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Journal Title
Hepatol Int.
Volume: -
Issue: 2
Pages: 366-379
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Repeated Administration of Kupffer Cells-Targeting Nanoantioxidant Ameliorates Liver Fibrosis in an Experimental Mouse Model2020
Author(s)
Maeda H, Minayoshi Y, Ichimizu S, Mizuta Y, Nagasaki T, Matsusaka K, Oshiro S, Oniki K, Saruwatari J, Ishima Y, Watanabe H, Otagiri M, Maruyama T.
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 43
Issue: 1
Pages: 93-101
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2020-01-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] ALT Levels for Asians With Metabolic Diseases: A Meta-analysis of 86 Studies With Individual Patient Data Validation.2020
Author(s)
Huang DQ, Yeo YH, Tan E, Takahashi H, Yasuda S, Saruwatari J, Tanaka K, Oniki K, Kam LY, Muthiah MD, Hyogo H, Ono M, Barnett SD, Li J, Zou B, Fung J, Lee TY, Wong VW, Yuen MF, Dan YY, Lim SG, Cheung R, Toyoda H, Eguchi Y, Nguyen MH.
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Journal Title
Hepatol Commun.
Volume: 4
Issue: 11
Pages: 1624-1636
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prostaglandin E2-EP4 axis promotes lipolysis and fibrosis in adipose tissue leading to ectopic fat deposition and insulin resistance.2020
Author(s)
Inazumi T, Yamada K, Shirata N, Sato H, Taketomi Y, Morita K, Hohjoh H, Tsuchiya S, Oniki K, Watanabe T, Sasaki Y, Oike Y, Ogata Y, Saruwatari J, Murakami M, Sugimoto Y.
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Journal Title
Cell Rep.
Volume: 33
Issue: 2
Pages: 108265-108265
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor Against Pathophysiological Decline of Lung Function2020
Author(s)
Fujikawa H, Sakamoto Y, Masuda N, Oniki K, Kamei S, Nohara H, Nakashima R, Maruta K, Kawakami T, Eto Y, Takahashi N, Takeo T, Nakagata N, Watanabe H, Otake K, Ogata Y, Tomioka NH, Hosoyamada M, Takada T, Ueno-Shuto K , Suico MA, Kai H, Saruwatari J, Shuto T.
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Journal Title
Antioxidants
Volume: 9
Issue: 5
Pages: 387-387
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The<I> DsbA-L</I> gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties.2020
Author(s)
Kentaro Oniki, Hirofumi Nohara, Ryunosuke Nakashima, Yui Obata, Narumi Muto, Yuki Sakamoto, Keiko Ueno-Shuto, Tadashi Imafuku, Yu Ishima, Hiroshi Watanabe, Toru Maruyama, Koji Otake, Yasuhiro Ogata, Mary Ann Suico, Hirofumi Kai, Tsuyoshi Shuto, and Junji Saruwatari.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 5973-5973
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cytotoxin-Associated Gene-A-Seropositivity and Interleukin-1 Polymorphisms Influence Adverse Cardiovascular Events.2020
Author(s)
Tabata N, SuetaD, Arima Y, Okamoto K, Shono T, Hanatani S, Takashio S, Oniki K, Saruwatari J, Sakamoto K, Kaikita K, Sinning JM, Werner K, Nickenig G, Sasaki Y, Fukui T, and Tsujita K.
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Journal Title
IJC Heart & Vasculature
Volume: -
Pages: 100498-100498
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions.2020
Author(s)
K. Oniki, T. Kawakami, A. Nakashima, K. Miyata, T. Watanabe, H. Fujikawa, R. Nakashima, A. Nasu, Y. Eto, N. Takahashi, H. Nohara, M. Ann Suico, S. Kotani, Y. Obata, Y. Sakamoto, Y. Seguchi, J. Saruwatari, T. Imafuku, H. Watanabe, T. Maruyama, H. Kai, T. Shuto
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Journal Title
Scientific reports
Volume: 10
Issue: 1
Pages: 4313-4313
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Pilot Study Assessing the Possible Combined Effect of Physical Activity and PNPLA3 rs738409 Polymorphism on the Risk for Non-Alcoholic Fatty Liver Disease in the Japanese Elderly General Population.2020
Author(s)
Muto N, Oniki K, Kudo M, Obata Y, Sakamoto Y, Tokumaru N, Izuka T, Watanabe T, Otake K, Ogata Y, Saruwatari J.
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Journal Title
Diabetes Metab Syndr Obes.
Volume: 13
Pages: 333-341
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Peer Reviewed / Open Access
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[Journal Article] Risk Evaluation for Acute Kidney Injury Induced by the Concomitant Use of Valacyclovir, Analgesics, and Renin-Angiotensin System Inhibitors: The Detection of Signals of Drug-Drug Interactions.2019
Author(s)
Inaba I, Kondo Y, Iwasaki S, Tsuruhashi S, Akaishi A, Morita K, Oniki K, Saruwatari J, Ishitsuka Y, Irie T.
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Journal Title
Front Pharmacol.
Volume: 10
Pages: 874-874
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Peer Reviewed / Open Access
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