日本人における２型糖尿病の遺伝的背景・成因を考慮した個別化予防システムの構築

• Project/Area Number: 16J09593
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: Applied health science (A)
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: 谷澤 薫平 国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所 身体活動研究部, 特別研究員(PD)
• Project Period (FY): 2016-04-22 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 2型糖尿病 / 遺伝子多型 / インスリン分泌能 / 非肥満者 / インスリン抵抗性 / 遺伝素因 / 肥満

Outline of Annual Research Achievements

本研究の目的は、個々の2型糖尿病の発症パターンを早期に予測するため、2型糖尿病の主要な成因であるインスリン分泌能低下とインスリン抵抗性を予測するための遺伝的リスクスコア(Genetic risk score: GRS)を構築し、GRSによる2型糖尿病発症パターンの分類を行うことと、これらGRSが2型糖尿病発症に及ぼす影響は、どのような生活習慣・身体特性を有する者において弱まるかを明らかにすることである。本年度は、2型糖尿病の既往歴のない中高齢者において、昨年度までに構築したインスリン分泌能低下を予測する遺伝的リスクスコア（insulin secretion-GRS [IS-GRS]）とインスリン分泌能および空腹時血糖値との関連は、全身持久力が高い者において弱まるかどうか、また、それらの関連はBMIが低い者においても認められるかどうかを明らかにすることを目的として研究を行った。
2型糖尿病の既往歴のない中高齢者882名を対象とした横断研究を行った。IS-GRSはインスリン分泌能との関連が報告されている20個のSNPより求めた。全身持久力は最大酸素摂取量の測定により評価した。BMIの中央値（BMI = 22.6 kg/m2）で対象者を高BMI群と低BMI群に分類し、それぞれの群において解析を行った。その結果、高BMI群においてIS-GRSと全身持久力との間に有意な交互作用が認められ、全身持久力が低い者においてはIS-GRSとインスリン分泌能および空腹時血糖値との間に有意な関連が認められたが、全身持久力が高い者においてはこれらの関連は認められなかった。しかし、低BMI群においてこれらの交互作用は認められなかった。
以上の結果より、インスリン分泌能と空腹時血糖値に及ぼす遺伝要因の影響は、BMIが低い者においては高い全身持久力を有していても弱まらない可能性が示唆された。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Altitude Training and Recombinant Human Erythropoietin: Considerations for Doping Detection. (2019)
  • Author(s): Sutehall S, Muniz-Pardos B, Lima G, Wang G, Malinsky FR, Bosch A, Zelenkova I, Tanisawa K, Pigozzi F, Borrione P, Pitsiladis Y
  • Journal Title: Current Sports Medicine Reports Volume: 18(4) Issue: 4 Pages: 97-104
  • DOI: 10.1249/jsr.0000000000000577
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Validity of an observational assessment tool for multifaceted evaluation of faecal condition (2019)
  • Author(s): Ohno Harumi、Murakami Haruka、Tanisawa Kumpei、Konishi Kana、Miyachi Motohiko
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 3760-3760
  • DOI: 10.1038/s41598-019-40178-5
  • Peer Reviewed / Open Access
• [Journal Article] Association of Serum 25-Hydroxyvitamin D Concentrations With Glucose Profiles in Male Collegiate Football Athletes (2019)
  • Author(s): Sun X, Cao ZB, Tanisawa K, Oshima S, Higuchi M
  • Journal Title: Int J Sport Nutr Exerc Metab Volume: 26 Issue: 4 Pages: 1-6
  • DOI: 10.1123/ijsnem.2018-0225
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dietary patterns and abdominal obesity in middle-aged and elderly Japanese adults: Waseda Alumni's Sports, Exercise, Daily Activity, Sedentariness and Health Study (WASEDA'S Health Study) (2019)
  • Author(s): Ito T, Kawakami R, Tanisawa K, Miyawaki R, Ishii K, Torii S, Suzuki K, Sakamoto S, Muraoka I, Oka K, Higuchi M; WASEDA'S Health Study Group
  • Journal Title: Nutrition Volume: 58 Pages: 149-155
  • DOI: 10.1016/j.nut.2018.05.029
  • Peer Reviewed / Open Access
• [Journal Article] Preexercise Carbohydrate Ingestion and Transient Hypoglycemia (2019)
  • Author(s): S. Kondo, K. Tanisawa, K. Suzuki, S. Terada, M. Higuchi
  • Journal Title: Fasting vs. Feeding. Med Sci Sports Exerc Volume: 51(1) Issue: 1 Pages: 168-168
  • DOI: 10.1249/mss.0000000000001773
  • Peer Reviewed / Open Access
• [Journal Article] Effects of short-term endurance exercise on gut microbiota in elderly men (2018)
  • Author(s): Taniguchi H, Tanisawa K, Sun X, Kubo T, Hoshino Y, Hosokawa M, Takeyama H, Higuchi M
  • Journal Title: Physiol Rep Volume: 6(23) Issue: 23 Pages: e13935-e13935
  • DOI: 10.14814/phy2.13935
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum 25-Hydroxyvitamin D Concentrations Are Inversely Correlated with Hepatic Lipid Content in Male Collegiate Football Athletes (2018)
  • Author(s): Sun X, Cao ZB, Tanisawa K, Oshima S, Higuchi M
  • Journal Title: Nutrients Volume: 10(7) Issue: 7 Pages: 942-942
  • DOI: 10.3390/nu10070942
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effects of Ingestion of Different Amounts of Carbohydrate after Endurance Exercise on Circulating Cytokines and Markers of Neutrophil Activation (2018)
  • Author(s): K Tanisaw, K Suzuki, S Ma, S Kondo, S Okugawa, M Higuchi
  • Journal Title: Antioxidants Volume: 7 Issue: 4 Pages: 51-51
  • DOI: 10.3390/antiox7040051
  • Peer Reviewed / Open Access
• [Journal Article] Inverse Association Between Height-Increasing Alleles and Extreme Longevity in Japanese Women. (2018)
  • Author(s): Tanisawa K, Hirose N, Arai Y, Shimokata H, Yamada Y, Kawai H, Kojima M, Obuchi S, Hirano H, Suzuki H, Fujiwara Y, Taniguchi Y, Shinkai S, Ihara K, Sugaya M, Higuchi M, Arai T, Mori S, Sawabe M, Sato N, Muramatsu M, Tanaka M.
  • Journal Title: J Gerontol A Biol Sci Med Sci Volume: 73(5) Issue: 5 Pages: 588-595
  • DOI: 10.1093/gerona/glx155
  • Peer Reviewed / Open Access
• [Journal Article] Effects of chronic endurance exercise training on serum 25(OH)D concentrations in elderly Japanese men (2017)
  • Author(s): Sun X, Cao ZB, Tanisawa K, Taniguchi H, Kubo T, Higuchi M
  • Journal Title: Endocrine Volume: 59(2) Issue: 2 Pages: 330-337
  • DOI: 10.1007/s12020-017-1478-z
  • Peer Reviewed
• [Journal Article] Effect of an Acute Bout of Endurance Exercise on Serum 25(OH)D Concentrations in Young Adults (2017)
  • Author(s): Sun X, Cao ZB, Taniguchi H, Tanisawa K, Higuchi M.
  • Journal Title: J Clin Endocrinol Metab Volume: 102(11) Issue: 11 Pages: 3937-3944
  • DOI: 10.1210/jc.2017-00146
  • Peer Reviewed
• [Journal Article] An Alpha-kinase 2 Gene Variant Disrupts Filamentous Actin Localization in the Surface Cells of Colorectal Cancer Spheroids (2017)
  • Author(s): Nishi K, Luo H, Nakabayashi K, Doi K, Ishikura S, Iwaihara Y, Yoshida Y, Tanisawa K, Arai T, Mori S, Sawabe M, Muramatsu M, Tanaka M, Sakata T, Shirasawa S, Tsunoda T
  • Journal Title: Anticancer Res Volume: 37(7) Pages: 3855-3862
  • Peer Reviewed
• [Journal Article] Method for preparing DNA from feces in guanidine thiocyanate solution affects 16S rRNA-based profiling of human microbiota diversity (2017)
  • Author(s): Hosomi Koji、Ohno Harumi、Murakami Haruka、Natsume-Kitatani Yayoi、Tanisawa Kumpei、Hirata Soichiro、Suzuki Hidehiko、Nagatake Takahiro、Nishino Tomomi、Mizuguchi Kenji、Miyachi Motohiko、Kunisawa Jun
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 4339-4339
  • DOI: 10.1038/s41598-017-04511-0
  • Peer Reviewed / Open Access
• [Journal Article] Visceral fat area is a strong predictor of leukocyte cell-derived chemotaxin 2, a potential biomarker of dyslipidemia (2017)
  • Author(s): Tanisawa K, Taniguchi H, Sun X, Ito T, Kawakami R, Sakamoto S, Higuchi M.
  • Journal Title: PLoS One Volume: 12(3) Issue: 3 Pages: e0173310-e0173310
  • DOI: 10.1371/journal.pone.0173310
  • Peer Reviewed / Open Access
• [Journal Article] Positive association between physical activity and PER3 expression in older adults (2017)
  • Author(s): Takahashi M, Haraguchi A, Tahara Y, Aoki N, Fukazawa M, Tanisawa K, Ito T, Nakaoka T, Higuchi M, Shibata S.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 39771-39771
  • DOI: 10.1038/srep39771
  • Peer Reviewed / Open Access
• [Journal Article] Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated with Extreme Longevity in East Asian Populations (2016)
  • Author(s): Kumpei Tanisawa, Masashi Tanaka, et al.
  • Journal Title: J Gerontol A Biol Sci Med Sci Volume: 00 Pages: 1-10
  • DOI: 10.1093/gerona/glw074
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Acute endurance exercise lowers serum fibroblast growth factor 21 levels in Japanese men (2016)
  • Author(s): Taniguchi H, Tanisawa K, Sun X, Higuchi M.
  • Journal Title: Clinical Endocrinology Volume: 85(6) Issue: 6 Pages: 861-867
  • DOI: 10.1111/cen.13162
  • Peer Reviewed
• [Journal Article] Vitamin D supplementation reduces insulin resistance in Japanese adults: a secondary analysis of a double-blind, randomized, placebo-controlled trial (2016)
  • Author(s): Sun X, Cao ZB, Tanisawa K, Ito T, Oshima S, Higuchi M.
  • Journal Title: Nutrition Research Volume: 36(10) Issue: 10 Pages: 1121-1129
  • DOI: 10.1016/j.nutres.2016.07.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic risk score based on the lifetime prevalence of femoral fracture in 1632 consecutive Japanese autopsy cases (2016)
  • Author(s): Heying Zhou, Seijiro Mori, Tatsuro Ishizaki, Masashi Tanaka, Kumpei Tanisawa, Makiko Naka-Mieno, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Yoshiji Yamada, Hideki Ito
  • Journal Title: J Bone Miner Metab Volume: 34 Issue: 6 Pages: 685-691
  • DOI: 10.1007/s00774-015-0718-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 中高年を対象とした食事調査票からの食事パターンの抽出と栄養素摂取量の評価 (2016)
  • Author(s): 伊藤 智子, 谷澤 薫平, 川上 諒子, 樋口 満
  • Journal Title: 日本公衆衛生雑誌 Volume: 63(11) Pages: 653-663
  • NAID: 130005180539
  • Peer Reviewed / Open Access
• [Presentation] Exploration of longevity and aging genes: Analyses of human and mouse exomes (2016)
  • Author(s): Tanisawa K, Tanaka M.
  • Organizer: 15th Korea-Japan Gerontologist Joint Meeting
  • Place of Presentation: Daegu, Korea
  • Year and Date: 2016-06-16
  • Int'l Joint Research / Invited
• [Presentation] Cardiorespiratory fitness and physical activity are not associated with plasma LECT2 levels (2016)
  • Author(s): Tanisawa K, Taniguchi H, Sun X, Ito T, Kawakami R, Sakamoto S, Higuchi M.
  • Organizer: 63th Annual Meeting and 7th World Congress on Exercise of the American College of Sports Medicine
  • Place of Presentation: Boston, Massachusetts, US
  • Year and Date: 2016-05-31
  • Int'l Joint Research