{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:12:46Z","timestamp":1778148766257,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Sphingosine-1-phosphate (S1P) is implicated in glycemic control. However, its circulating levels and clinical significance in type 2 diabetes mellitus (T2DM) remain controversial. We assessed plasma S1P levels in T2DM patients, its associations with metabolic parameters and complications, and explored its biomarker potential and non-linear (U-\/J-shaped) relationships. Methods: This cross-sectional study enrolled 140 patients with T2DM and 63 matching healthy controls. Plasma S1P was measured by competitive ELISA. Statistical analyses included comparisons, correlation, ROC analysis, multivariable logistic regression, and quadratic\/spline regression for U-shaped relationships. Results: Plasma S1P was significantly elevated in T2DM patients [1256.7 (149.4\u20131510.0) ng\/mL] compared to controls [1075.1 (202.0\u20131510.0) ng\/mL; p &lt; 0.001]. S1P correlated positively with age, disease duration, HbA1c, insulin resistance, TyG index, triglycerides, systolic blood pressure, and negatively with HDL-C. Patients with complications had higher S1P than those without (p = 0.001), with progressive increases from retinopathy to nephropathy to mixed complications. Insulin-treated patients exhibited the highest S1P levels (p &lt; 0.001). ROC analysis showed moderate diagnostic accuracy (AUC = 0.724). S1P is an independent associated factor with complications (OR = 1.18 per 100 ng\/mL, p = 0.003). Non-linear analysis revealed a U-shaped relationship with HDL-C (optimal S1P: 1100\u20131350 ng\/mL) and a J-shaped relationship with complication risk (threshold ~1250 ng\/mL). Conclusions: Plasma S1P is elevated in T2DM and correlates with disease severity, glycemic control, insulin resistance, and complications. S1P demonstrates moderate biomarker potential and exhibits non-linear U-\/J-shaped relationships with metabolic parameters, suggesting an optimal therapeutic window of 1100\u20131280 ng\/mL. These findings support S1P as a marker of cumulative disease burden and a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/jcm15093233","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:04:59Z","timestamp":1776963899000},"page":"3233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Higher Plasma Sphingosine-1-Phosphate Levels in Type 2 Diabetic Patients Have a Non-Linear Relationship with the Disease Prognostic Indices and Microvascular Complications: A Cross-Sectional Saudi Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-0980","authenticated-orcid":false,"given":"Basil M.","family":"Alomair","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/18756417OTg2dNzMaTcVY","article-title":"The worrying trend of diabetes mellitus in Saudi Arabia: An urgent call to action","volume":"16","author":"Robert","year":"2020","journal-title":"Curr. 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