{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:35:06Z","timestamp":1778013306678,"version":"3.51.4"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar Research Development and Innovation (QRDPI) Council","award":["PPM 06-0516-230030"],"award-info":[{"award-number":["PPM 06-0516-230030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), especially in Middle Eastern populations with a high metabolic burden. This study aimed to evaluate the predictive utility of different lipid ratios, including triglyceride-to-high-density lipoprotein cholesterol (TG\/HDL-C), total cholesterol (TC)\/HDL-C, low-density lipoprotein (LDL-C)\/HDL-C, and non-HDL-C\/HDL-C, for identifying MetS. In addition, we aimed to characterise the underlying metabolic dysregulation using the most predictive lipid ratio by comparing metabolomic profiles between high-risk (T3) and low-risk (T1) groups. Method: We conducted a cross-sectional study using data from 2179 Qatari adults without CVD and\/or T2DM. The predictive value of each lipid ratio for MetS was compared. Untargeted metabolomics was performed to profile metabolic changes between T3 and T1. Results: After adjustment for age, sex, and BMI, TG\/HDL-C showed the highest discriminative ability for MetS (AUC = 0.896, 95% CI: 0.88\u20130.91; OR = 4.36, 95% CI: 3.63\u20135.28, p &lt; 0.0001). In pairwise AUC comparisons, TG\/HDL-C outperformed LDL-C\/HDL-C (p = 2.6 \u00d7 10\u22124, after correction for multiple comparisons), with no significant differences versus other ratios. The high-risk group exhibited raised levels of phosphatidylethanolamines, phosphatidylinositols, and diacylglycerols, and lower levels of sphingomyelins and plasmalogens. These lipid classes have been suggested to be implicated in insulin resistance and metabolic dysfunction. Elevated monoacylglycerols were identified in high-TG\/HDL-C groups, representing a previously underreported pattern. Conclusions: The TG\/HDL-C ratio showed a better association with MetS compared with other lipid ratios and was linked to distinct metabolomic signatures. These findings suggest potential value for early risk evaluation, but longitudinal and mechanistic studies are needed to confirm clinical applicability.<\/jats:p>","DOI":"10.3390\/metabo15090574","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T10:29:18Z","timestamp":1756376958000},"page":"574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Predictive Utility and Metabolomic Signatures of TG\/HDL-C Ratio for Metabolic Syndrome Without Cardiovascular Disease and\/or Diabetes in Qatari Adults"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0553-4008","authenticated-orcid":false,"given":"Noora","family":"Kano","sequence":"first","affiliation":[{"name":"Military Medical City Hospital, Medical Services, Qatar Armed Forces, Doha P.O. Box 2352, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-4905","authenticated-orcid":false,"given":"Najeha","family":"Anwardeen","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9259-3082","authenticated-orcid":false,"given":"Khaled","family":"Naja","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6927-5622","authenticated-orcid":false,"given":"Asma A.","family":"Elashi","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9722-2336","authenticated-orcid":false,"given":"Ahmed","family":"Malki","sequence":"additional","affiliation":[{"name":"Biomedical Science Department, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-4604","authenticated-orcid":false,"given":"Mohamed A.","family":"Elrayess","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21501319241309168","DOI":"10.1177\/21501319241309168","article-title":"Metabolic Syndrome: An Updated Review on Diagnosis and Treatment for Primary Care Clinicians","volume":"15","author":"Peterseim","year":"2024","journal-title":"J. Prim. Care Community Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.jacc.2010.05.034","article-title":"The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis","volume":"56","author":"Mottillo","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lee, M.-K., Han, K., Kim, M.K., Koh, E.S., Kim, E.S., Nam, G.E., and Kwon, H.-S. (2020). 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