{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:11:16Z","timestamp":1772518276499,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T00:00:00Z","timestamp":1684627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danone Institutes Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This study aimed to identify the serum metabolites associated with sarcopenic risk in Japanese patients with type 2 diabetes, determine the effect of dietary protein intake on the serum metabolic profile, and examine its association with sarcopenia. Ninety-nine Japanese patients with type 2 diabetes were included, and sarcopenic risk was defined as low muscle mass or strength. Seventeen serum metabolites were quantified after gas chromatography\u2013mass spectrometry analysis. The relationship between dietary protein intake and the metabolites concerning sarcopenia was analyzed, and the factors affecting sarcopenic risk were clarified. Twenty-seven patients were classified as being at risk of sarcopenia, the same as the general risk, which was associated with older age, a longer duration of the disease, and a lower body mass index. Low levels of leucine and glutamic acid were significantly associated with low muscle strength (p = 0.002 and p &lt; 0.001, respectively), and leucine was also associated with muscle mass (p = 0.001). Lower levels of glutamic acid had higher odds of sarcopenic risk after being adjusted for age and HbA1c (adjusted OR 4.27, 95% CI 1.07\u201317.11, p = 0.041), but not for leucine. Leucine and glutamic acid can serve as useful biomarkers for sarcopenia, highlighting potential targets for its prevention.<\/jats:p>","DOI":"10.3390\/nu15102400","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:00:27Z","timestamp":1684720827000},"page":"2400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-1790","authenticated-orcid":false,"given":"Hanako","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1707-970X","authenticated-orcid":false,"given":"Hiroshi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyuko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Nutrition Division, Saiseikai Suita Hospital, Osaka 564-0013, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-1697","authenticated-orcid":false,"given":"Takuro","family":"Okamura","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-0550","authenticated-orcid":false,"given":"Yoshitaka","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Osaka 570-8540, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Senmaru","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1031-4380","authenticated-orcid":false,"given":"Emi","family":"Ushigome","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-4445","authenticated-orcid":false,"given":"Masahide","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-1797","authenticated-orcid":false,"given":"Michiaki","family":"Fukui","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Andreadi, A., Muscoli, S., Tajmir, R., Meloni, M., Muscoli, C., Ilari, S., Mollace, V., Della Morte, D., Bellia, A., and Di Daniele, N. (2023). Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021646"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1900\/RDS.2022.18.157","article-title":"Sarcopenia and Chronic Complications of Type 2 Diabetes Mellitus","volume":"18","author":"Purnamasari","year":"2022","journal-title":"Rev. Diabet. Stud."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Izzo, A., Massimino, E., Riccardi, G., and Della, P. (2021). A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors. Nutrients, 13.","DOI":"10.3390\/nu13010183"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/ggi.12189","article-title":"Type 2 Diabetes Is Associated with Low Muscle Mass in Older Adults","volume":"14","author":"Kim","year":"2014","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pollakova, D., Tubili, C., Folco, U., Giuseppe, R., Battino, M., and Giampieri, F. (2023). Muscular Involvement in Long Term Type 1 Diabetes: Does It Represent an Underestimated Complication?. Nutrition, 112060. in press.","DOI":"10.1016\/j.nut.2023.112060"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/ggi.13643","article-title":"Synergistic Effect of Bodyweight Resistance Exercise and Protein Supplementation on Skeletal Muscle in Sarcopenic or Dynapenic Older Adults","volume":"19","author":"Yamada","year":"2019","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Amasene, M., Besga, A., Echeverria, I., Urquiza, M., Ruiz, J.R., Rodriguez-Larrad, A., Aldamiz, M., Anaut, P., Irazusta, J., and Labayen, I. (2019). Effects of Leucine-Enriched Whey Protein Supplementation on Physical Function in Post-Hospitalized Older Adults Participating in 12-Weeks of Resistance Training Program: A Randomized Controlled Trial. Nutrients, 11.","DOI":"10.3390\/nu11102337"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jamda.2019.09.006","article-title":"Effect of Protein Supplementation on Physical Performance in Older People With Sarcopenia-A Randomized Controlled Trial","volume":"21","author":"Suominen","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1017\/S0007114514002475","article-title":"The Effectiveness of Leucine on Muscle Protein Synthesis, Lean Body Mass and Leg Lean Mass Accretion in Older People: A Systematic Review and Meta-Analysis","volume":"113","author":"Xu","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109336","DOI":"10.1016\/j.celrep.2021.109336","article-title":"Distribution of Dietary Protein Intake in Daily Meals Influences Skeletal Muscle Hypertrophy via the Muscle Clock","volume":"36","author":"Aoyama","year":"2021","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111924","DOI":"10.1016\/j.exger.2022.111924","article-title":"Metabolomic Profiles to Explore Biomarkers of Severe Sarcopenia in Older Men: A Pilot Study","volume":"167","author":"Shin","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Calvani, R., Picca, A., Marini, F., Biancolillo, A., Gervasoni, J., Persichilli, S., Primiano, A., Coelho-Junior, H., Bossola, M., and Urbani, A. (2018). A Distinct Pattern of Circulating Amino Acids Characterizes Older Persons with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study. Nutrients, 10.","DOI":"10.20944\/preprints201809.0224.v1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1111\/jdi.13459","article-title":"Impact of Extracellular-to-intracellular Fluid Volume Ratio on Albuminuria in Patients with Type 2 Diabetes: A Cross-sectional and Longitudinal Cohort Study","volume":"12","author":"Nakajima","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/ggi.13577","article-title":"Sarcopenia Is Associated with Tongue Pressure in Older Patients with Type 2 Diabetes: A Cross-Sectional Study of the KAMOGAWA-DM Cohort Study: Sarcopenia and Tongue Pressure","volume":"19","author":"Kaji","year":"2019","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1381\/0960892054621350","article-title":"Estimating Ideal Body Weight\u2014A New Formula","volume":"15","author":"Lemmens","year":"2005","journal-title":"Obes. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1046\/j.1532-5415.2002.50216.x","article-title":"Low Relative Skeletal Muscle Mass (Sarcopenia) in Older Persons Is Associated with Functional Impairment and Physical Disability","volume":"50","author":"Janssen","year":"2002","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jamda.2019.12.012","article-title":"Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment","volume":"21","author":"Chen","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12986-022-00685-1","article-title":"Inulin Reduces Visceral Adipose Tissue Mass and Improves Glucose Tolerance through Altering Gut Metabolites","volume":"19","author":"Nakajima","year":"2022","journal-title":"Nutr. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1016\/S2666-7568(23)00001-6","article-title":"Multimarkers of Metabolic Malnutrition and Inflammation and Their Association with Mortality Risk in Cardiac Catheterisation Patients: A Prospective, Longitudinal, Observational, Cohort Study","volume":"4","author":"Otvos","year":"2023","journal-title":"Lancet Healthy Longev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1152\/japplphysiol.91397.2008","article-title":"Nutritional and Contractile Regulation of Human Skeletal Muscle Protein Synthesis and MTORC1 Signaling","volume":"106","author":"Drummond","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"685165","DOI":"10.3389\/fnut.2021.685165","article-title":"Evaluating the Leucine Trigger Hypothesis to Explain the Post-Prandial Regulation of Muscle Protein Synthesis in Young and Older Adults: A Systematic Review","volume":"8","author":"Zaromskyte","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1249\/00003677-199800260-00013","article-title":"Muscle Amino Acid Metabolism at Rest and during Exercise: Role in Human Physiology and Metabolism","volume":"26","author":"Wagenmakers","year":"1998","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1824S","DOI":"10.1093\/jn\/135.7.1824S","article-title":"Metabolic Consequences of Muscle Disuse Atrophy","volume":"135","author":"Stein","year":"2005","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.biocel.2016.08.012","article-title":"Cessation of Biomechanical Stretch Model of C2C12 Cells Models Myocyte Atrophy and Anaplerotic Changes in Metabolism Using Non-Targeted Metabolomics Analysis","volume":"79","author":"Ilaiwy","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Picca, A., Calvani, R., Cesari, M., Landi, F., Bernabei, R., Coelho-J\u00fanior, H.J., and Marzetti, E. (2020). Biomarkers of Physical Frailty and Sarcopenia: Coming up to the Place?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165635"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.18632\/aging.203926","article-title":"Pathway-Based Metabolomics Study of Sarcopenia-Related Traits in Two US Cohorts","volume":"14","author":"Zhao","year":"2022","journal-title":"Aging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/j.clnu.2017.10.009","article-title":"Citrulline in Health and Disease. Review on Human Studies","volume":"37","author":"Papadia","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1007\/s00726-011-1172-z","article-title":"Effects of Leucine and Citrulline versus Non-Essential Amino Acids on Muscle Protein Synthesis in Fasted Rat: A Common Activation Pathway?","volume":"43","author":"Walrand","year":"2012","journal-title":"Amino Acids"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lu, Y., Wang, Y., Liang, X., Zou, L., Ong, C., Yuan, J.-M., Koh, W.-P., and Pan, A. (2019). Serum Amino Acids in Association with Prevalent and Incident Type 2 Diabetes in A Chinese Population. Metabolites, 9.","DOI":"10.3390\/metabo9010014"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Yun, J.H., Lee, H.-S., Yu, H.-Y., Kim, Y.-J., Jeon, H.J., Oh, T., Kim, B.-J., Choi, H.J., and Kim, J.-M. (2019). Metabolomics Profiles Associated with HbA1c Levels in Patients with Type 2 Diabetes. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224274"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1210\/endrev\/bnaa025","article-title":"Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease","volume":"42","author":"Horton","year":"2021","journal-title":"Endocr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3389\/fphar.2020.00779","article-title":"Insulin and Exendin-4 Reduced Mutated Huntingtin Accumulation in Neuronal Cells","volume":"11","author":"Rea","year":"2020","journal-title":"Front. Pharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/10\/2400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:39:19Z","timestamp":1760125159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/10\/2400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,21]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["nu15102400"],"URL":"https:\/\/doi.org\/10.3390\/nu15102400","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,21]]}}}