{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:59:20Z","timestamp":1792133960261,"version":"4.4.0"},"reference-count":80,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM.<\/jats:p>","DOI":"10.3390\/ijms26157574","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diabetes and Sarcopenia: Metabolomic Signature of Pathogenic Pathways and Targeted Therapies"],"prefix":"10.3390","volume":"26","author":[{"given":"Anamaria Andreea","family":"Danciu","sequence":"first","affiliation":[{"name":"Ph.D. School, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"},{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6216-9088","authenticated-orcid":false,"given":"Cornelia","family":"Bala","sequence":"additional","affiliation":[{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"},{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1624-6916","authenticated-orcid":false,"given":"Georgeta","family":"Inceu","sequence":"additional","affiliation":[{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"},{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia Larisa","family":"Vonica","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0977-8874","authenticated-orcid":false,"given":"Adriana","family":"Rusu","sequence":"additional","affiliation":[{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"},{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5981-5672","authenticated-orcid":false,"given":"Gabriela","family":"Roman","sequence":"additional","affiliation":[{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"},{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-6110","authenticated-orcid":false,"given":"Dana Mihaela","family":"Ciobanu","sequence":"additional","affiliation":[{"name":"Diabetes Center, Emergency Clinical County Hospital Cluj, 400006 Cluj-Napoca, Romania"},{"name":"Department of Diabetes and Nutrition Diseases, \u201cIuliu Ha\u1e6dieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","unstructured":"(2025, June 02). IDF Diabetes Atlas 2025|Global Diabetes Data & Insights. Available online: https:\/\/diabetesatlas.org\/resources\/idf-diabetes-atlas-2025\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s44197-023-00138-9","article-title":"The Description and Prediction of Incidence, Prevalence, Mortality, Disability-Adjusted Life Years Cases, and Corresponding Age-Standardized Rates for Global Diabetes","volume":"13","author":"Sun","year":"2023","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s40520-025-02995-9","article-title":"Health outcomes of sarcopenia: A consensus report by the outcome working group of the Global Leadership Initiative in Sarcopenia (GLIS)","volume":"37","author":"Beaudart","year":"2025","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4093\/dmj.2023.0112","article-title":"Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies","volume":"47","author":"Mesinovic","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.2147\/DMSO.S410834","article-title":"The Association Between Sarcopenia and Diabetes: From Pathophysiology Mechanism to Therapeutic Strategy","volume":"16","author":"Chen","year":"2023","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/jdi.13752","article-title":"Sarcopenia in elderly diabetes","volume":"13","author":"Wen","year":"2022","journal-title":"J. Diabetes Investig."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lisco, G., Disoteo, O.E., De Tullio, A., De Geronimo, V., Giagulli, V.A., Monzani, F., Jirillo, E., Cozzi, R., Guastamacchia, E., and De Pergola, G. (2024). Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age. Nutrients, 16.","DOI":"10.3390\/nu16010063"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1159\/000530241","article-title":"Higher Risk of Sarcopenia in Older Adults with Type 2 Diabetes: NHANES 1999\u20132018","volume":"16","author":"Dai","year":"2023","journal-title":"Obes. Facts"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s41999-019-00216-x","article-title":"Association between sarcopenia and diabetes: A systematic review and meta-analysis of observational studies","volume":"10","author":"Veronese","year":"2019","journal-title":"Eur. Geriatr. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhan, Z., Zhang, Y., Wu, J., Lin, J., and Yan, S. (2025). Predictive efficacy of different diagnostic criteria for sarcopenia in osteoporosis and fractures. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-93988-1"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Al-Akl, N.S., Khalifa, O., Ponirakis, G., Parray, A., Ramadan, M., Khan, S., Chandran, M., Ayadathil, R., Elsotouhy, A., and Own, A. (2024). Untargeted Metabolomic Profiling Reveals Differentially Expressed Serum Metabolites and Pathways in Type 2 Diabetes Patients with and without Cognitive Decline: A Cross-Sectional Study. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042247"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bala, C., Rusu, A., Ciobanu, D.M., Roman, G., and Cr\u0103ciun, A.E. (2025). Metabolomics in Pathogenic Pathways and Targeted Therapies for Diabetic Neuropathy: A Comprehensive Review. Metabolites, 15.","DOI":"10.3390\/metabo15020086"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Han, P., Chen, X., Liang, Z., Liu, Y., Yu, X., Song, P., Zhao, Y., Zhang, H., Zhu, S., and Shi, X. (2024). Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS\u2013based untargeted metabonomics. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1308841"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1002\/jcsm.13567","article-title":"Novel metabolic and lipidomic biomarkers of sarcopenia","volume":"15","author":"Hsu","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13395-022-00312-w","article-title":"Sarcopenia: Investigation of metabolic changes and its associated mechanisms","volume":"13","author":"Marques","year":"2023","journal-title":"Skelet. Muscle"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alldritt, I., Greenhaff, P.L., and Wilkinson, D.J. (2021). Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413575"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mathioudaki, A., Fanni, G., Eriksson, J.W., and Pereira, M.J. (2024). Metabolomic Profiling of Adipose Tissue in Type 2 Diabetes: Associations with Obesity and Insulin Resistance. Metabolites, 14.","DOI":"10.3390\/metabo14080411"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hammad, S.M., and Lopes-Virella, M.F. (2023). Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202308.1042.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1139\/cjpp-2024-0201","article-title":"Sarcopenia: Recent advances for detection, progression, and metabolic alterations along with therapeutic targets","volume":"102","author":"Ali","year":"2024","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114056","DOI":"10.1016\/j.intimp.2025.114056","article-title":"The role of chronic low-grade inflammation in the development of sarcopenia: Advances in molecular mechanisms","volume":"147","author":"Cheng","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tan, Y., Liu, X., Yang, Y., Li, B., Yu, F., Zhao, W., Fu, C., Yu, X., Han, Z., and Cheng, M. (2023). Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1119782"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xiao, W., Huang, T.E., Zhou, J., Wang, B., Wang, X., Zeng, W., Wang, Q., Lan, X., and Xiang, Y. (2024). Inhibition of MAT2A Impairs Skeletal Muscle Repair Function. Biomolecules, 14.","DOI":"10.3390\/biom14091098"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8846","DOI":"10.1002\/fsn3.4449","article-title":"Isoxanthohumol improves hepatic lipid metabolism via regulating the AMPK\/PPAR\u03b1 and PI3K\/AKT signaling pathways in hyperlipidemic mice","volume":"12","author":"Gao","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhou, M., Wei, Y., Feng, Y., Zhang, S., Ma, N., Wang, K., Tan, P., Zhao, Y., Zhao, J., and Ma, X. (2024). Arginine Regulates Skeletal Muscle Fiber Type Formation via mTOR Signaling Pathway. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116184"},{"key":"ref_26","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_27","doi-asserted-by":"crossref","unstructured":"Nakajima, H., Okada, H., Kobayashi, A., Takahashi, F., Okamura, T., Hashimoto, Y., Nakanishi, N., Senmaru, T., Ushigome, E., and Hamaguchi, M. (2023). Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes. Nutrients, 15.","DOI":"10.3390\/nu15102400"},{"key":"ref_28","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_29","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_30","doi-asserted-by":"crossref","unstructured":"Toyoshima, K., Nakamura, M., Adachi, Y., Imaizumi, A., Hakamada, T., Abe, Y., Kaneko, E., Takahashi, S., and Shimokado, K. (2017). Increased plasma proline concentrations are associated with sarcopenia in the elderly. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185206"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"sfae366","DOI":"10.1093\/ckj\/sfae366","article-title":"Frailty and sarcopenia metabolomic signatures in kidney transplant candidates: The FRAILMar study","volume":"18","author":"Haro","year":"2025","journal-title":"Clin. Kidney J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e14410","DOI":"10.1111\/acel.14410","article-title":"Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women","volume":"24","author":"Yao","year":"2025","journal-title":"Aging Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Saoi, M., Li, A., McGlory, C., Stokes, T., von Allmen, M.T., Phillips, S.M., and Britz-McKibbin, P. (2019). Metabolic Perturbations from Step Reduction in Older Persons at Risk for Sarcopenia: Plasma Biomarkers of Abrupt Changes in Physical Activity. Metabolites, 9.","DOI":"10.3390\/metabo9070134"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109803","DOI":"10.1016\/j.diabres.2022.109803","article-title":"Amino acid profile of skeletal muscle loss in type 2 diabetes: Results from a 7-year longitudinal study in asians","volume":"186","author":"Low","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1017\/S0007114518001307","article-title":"Reduced plasma concentration of branched-chain amino acids in sarcopenic older subjects: A cross-sectional study","volume":"120","author":"Ottestad","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Liu, H., Zhang, Q., Hao, Q., Li, Q., Yang, L., Yang, X., Wang, K., Teng, J., Gong, Z., and Jia, Y. (2024). Associations between sarcopenia and circulating branched-chain amino acids: A cross-sectional study over 100,000 participants. BMC Geriatr., 24.","DOI":"10.1186\/s12877-024-05144-5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12603-018-1108-3","article-title":"Low Levels of Branched Chain Amino Acids, Eicosapentaenoic Acid and Micronutrients are Associated with Low Muscle Mass, Strength and Function in Community-Dwelling Older Adults","volume":"23","author":"Luiking","year":"2019","journal-title":"J. Nutr. Health Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"bvad178","DOI":"10.1210\/jendso\/bvad178","article-title":"Association of Elevated Serum Branched-chain Amino Acid Levels With Longitudinal Skeletal Muscle Loss","volume":"8","author":"Imai","year":"2024","journal-title":"J. Endocr. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, C.W.D., Herpich, C., Ha\u00df, U., Kochlik, B., Weber, D., Grune, T., and Norman, K. (2025). Essential amino acids and branched-chain amino acids are associated with skeletal muscle and inflammatory parameters in older age. Biogerontology, 26.","DOI":"10.1007\/s10522-025-10206-1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"34056","DOI":"10.1021\/acsomega.4c04668","article-title":"Proteomics Analysis Provides Insights into the Role of Lipid Metabolism in T2DM-Related Sarcopenia","volume":"9","author":"Wu","year":"2024","journal-title":"ACS Omega"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1002\/jcsm.13550","article-title":"A multi-omics approach to overeating and inactivity-induced muscle atrophy in db\/db mice","volume":"15","author":"Okamura","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Huang, Y.C., Sanotra, M.R., Huang, C.C., Hsu, Y.J., and Liao, C.C. (2024). Aerobic Exercise Modulates Proteomic Profiles in Gastrocnemius Muscle of db\/db Mice, Ameliorating Sarcopenia. Life, 14.","DOI":"10.3390\/life14030412"},{"key":"ref_43","first-page":"5064","article-title":"Intramuscular accumulation of pentadecanoic acid activates AKT1 to phosphorylate NCOR1 and triggers FOXM1-mediated apoptosis in the pathogenesis of sarcopenia","volume":"12","author":"Chen","year":"2020","journal-title":"Am. J. Transl. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Losasso, M.R., Parussolo, M.L.C., Oliveira Silva, A., Direito, R., Quesada, K., Penteado Detregiachi, C.R., Bechara, M.D., M\u00e9ndez-S\u00e1nchez, N., Abenavoli, L., and Ara\u00fajo, A.C. (2025). Unraveling the Metabolic Pathways Between Metabolic-Associated Fatty Liver Disease (MAFLD) and Sarcopenia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104673"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12072-022-10439-z","article-title":"Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people","volume":"17","author":"Zhu","year":"2023","journal-title":"Hepatol. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1002\/jcsm.13582","article-title":"Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men","volume":"15","author":"Seo","year":"2024","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1093\/gerona\/gly100","article-title":"Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging","volume":"74","author":"Moaddel","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e33601","DOI":"10.1016\/j.heliyon.2024.e33601","article-title":"Lysophosphatidylcholine trigger myocardial injury in diabetic cardiomyopathy via the TLR4\/ZNF480\/AP-1\/NF-kB pathway","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.2147\/DMSO.S371370","article-title":"Lysophosphatidylcholine (17:0) Improves HFD-Induced Hyperglycemia & Insulin Resistance: A Mechanistic Mice Model Study","volume":"15","author":"Bao","year":"2022","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1093\/gerona\/gly051","article-title":"Impaired Mitochondrial Energetics Characterize Poor Early Recovery of Muscle Mass Following Hind Limb Unloading in Old Mice","volume":"73","author":"Zhang","year":"2018","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Romanello, V., and Sandri, M. (2016). Mitochondrial Quality Control and Muscle Mass Maintenance. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00422"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cmet.2007.10.013","article-title":"Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance","volume":"7","author":"Koves","year":"2008","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00421-017-3730-x","article-title":"Targeting mitochondrial function and proteostasis to mitigate dynapenia","volume":"118","author":"Musci","year":"2018","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/jcsm.12777","article-title":"Ablation of USP21 in skeletal muscle promotes oxidative fibre phenotype, inhibiting obesity and type 2 diabetes","volume":"12","author":"Kim","year":"2021","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Moriggi, M., Belloli, S., Barbacini, P., Murtaj, V., Torretta, E., Chaabane, L., Canu, T., Penati, S., Malosio, M.L., and Esposito, A. (2021). Skeletal muscle proteomic profile revealed gender-related metabolic responses in a diet-induced obesity animal model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094680"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Calvani, R., Picca, A., Rodriguez-Ma\u00f1as, L., Tosato, M., Coelho-J\u00fanior, H.J., Biancolillo, A., Laosa, O., Gervasoni, J., Primiano, A., and Santucci, L. (2023). Amino Acid Profiles in Older Adults with Frailty: Secondary Analysis from MetaboFrail and BIOSPHERE Studies. Metabolites, 13.","DOI":"10.3390\/metabo13040542"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lee, D., Kim, S.J., Choi, Y.J., Rho, Y.H., Kang, T.S., Kim, Y.G., and Kang, K.S. (2025). The Glucose-Lowering Effect of Mesembryanthemum crystallinum and D-Pinitol: Studies on Insulin Secretion in INS-1 Cells and the Reduction of Blood Glucose in Diabetic Rats. Nutrients, 17.","DOI":"10.3390\/nu17010193"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s42269-022-00820-1","article-title":"Effects of d-pinitol on diabetes mellitus: An updated review","volume":"46","author":"Pandi","year":"2022","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"14466","DOI":"10.1021\/acs.jafc.4c03929","article-title":"d-Pinitol Improves Diabetic Sarcopenia by Regulation of the Gut Microbiome, Metabolome, and Proteome in STZ-Induced SAMP8 Mice","volume":"72","author":"Yu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"E1341","DOI":"10.1152\/ajpendo.00095.2006","article-title":"Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance","volume":"291","author":"Turpin","year":"2006","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Tan-Chen, S., Guitton, J., Bourron, O., Le Stunff, H., and Hajduch, E. (2020). Sphingolipid Metabolism and Signaling in Skeletal Muscle: From Physiology to Physiopathology. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00491"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sawicka, A.K., Hartmane, D., Lipinska, P., Wojtowicz, E., Lysiak-Szydlowska, W., and Olek, R.A. (2018). l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function. Nutrients, 10.","DOI":"10.3390\/nu10020255"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Elgizawy, E.I., Amer, G.S., Ali, E.A., Alqalashy, F.S., Ibrahim, M.M., Latif, A.A.A., and Shaban, A.M. (2024). Comparing the efficacy of concomitant treatment of resistance exercise and creatine monohydrate versus multiple individual therapies in age related sarcopenia. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-59884-w"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1038\/s41467-024-47843-y","article-title":"Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes","volume":"15","author":"Mezincescu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Sarma, M.K., Saucedo, A., Sadananthan, S.A., Darwin, C.H., Felker, E.R., Raman, S., Velan, S.S., and Thomas, M. (2025). Lipid Deposition in Skeletal Muscle Tissues and Its Correlation with Intra-Abdominal Fat: A Pilot Investigation in Type 2 Diabetes Mellitus. Metabolites, 15.","DOI":"10.3390\/metabo15010025"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.freeradbiomed.2024.01.015","article-title":"Cardiovascular benefits of SGLT2 inhibitors and GLP-1 receptor agonists through effects on mitochondrial function and oxidative stress","volume":"213","author":"Iannantuoni","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Yal\u00e7\u0131n, N., Akta\u015f, S., Uyar, S., and Koca, N. (2025). Impact of SGLT2 Inhibitors on Cardiovascular Risk Scores, Metabolic Parameters, and Laboratory Profiles in Type 2 Diabetes. Life, 15.","DOI":"10.3390\/life15050722"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.56782\/pps.176","article-title":"SGLT2 inhibitors and their possible use in prevention and treatment of neurological diseases","volume":"22","author":"Sobczyk","year":"2024","journal-title":"Prospect. Pharm. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"629637","DOI":"10.1155\/2012\/629637","article-title":"Intramuscular adipose tissue, sarcopenia, and mobility function in older individuals","volume":"2012","author":"Marcus","year":"2012","journal-title":"J. Aging Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/jcsm.12814","article-title":"Extracellular lipidome change by an SGLT2 inhibitor, luseogliflozin, contributes to prevent skeletal muscle atrophy in db\/db mice","volume":"13","author":"Bamba","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1042\/BCJ20210700","article-title":"Differential effect of canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on slow and fast skeletal muscles from nondiabetic mice","volume":"479","author":"Otsuka","year":"2022","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1002\/jcsm.13350","article-title":"Improved endurance capacity of diabetic mice during SGLT2 inhibition: Role of AICARP, an AMPK activator in the soleus","volume":"14","author":"Nakamura","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s13668-025-00649-w","article-title":"Impact of GLP-1 Receptor Agonist Therapy in Patients High Risk for Sarcopenia","volume":"14","author":"Memel","year":"2025","journal-title":"Curr. Nutr. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"156113","DOI":"10.1016\/j.metabol.2024.156113","article-title":"Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis","volume":"164","author":"Karakasis","year":"2025","journal-title":"Metabolism"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Park, S., Oh, S., and Kim, E.K. (2022). Glucagon-like peptide-1 analog liraglutide leads to multiple metabolic alterations in diet-induced obese mice. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102682"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.2147\/DDDT.S381546","article-title":"An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism","volume":"16","author":"Ren","year":"2022","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.2147\/DMSO.S425642","article-title":"GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway","volume":"16","author":"Xiang","year":"2023","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"102172","DOI":"10.1016\/j.jsps.2024.102172","article-title":"Untargeted metabolomics reveals the impact of Liraglutide treatment on metabolome profiling and metabolic pathways in type-2 diabetes mellitus","volume":"32","author":"Benabdelkamel","year":"2024","journal-title":"Saudi Pharm. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1186\/s12957-022-02854-1","article-title":"Laparoscopic liver resection is associated with less significant muscle loss than the conventional open approach","volume":"20","author":"Gau","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Gaglio, A., Grancini, V., Giacchetti, F., Mirani, M., Orsi, E., and Resi, V. (2025). Role of Medical Nutrition Therapy as Treatment of Sarcopenia in Older People with Type 2 Diabetes. Nutrients, 17.","DOI":"10.3390\/nu17010172"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7574\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:23:46Z","timestamp":1760034226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/15\/7574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,5]]},"references-count":80,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26157574"],"URL":"https:\/\/doi.org\/10.3390\/ijms26157574","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,5]]}}}