ArticleCardiovascular diabetology2024
Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07287514 (Role of Linoleic Acid in Cardiometabolic Health Beyond Its Lipid-lowering Effects, and Its Dietary and Pathophysiological Implications), which is not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Role of Linoleic Acid in Cardiometabolic Health Beyond Its Lipid-lowering Effects, and Its Dietary and Pathophysiological Implications
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Metabolomics profile in diabetes and blood glucose regulation: a systematic review.Frontiers in nutrition · 2026Pooled it
- First-Line Dapagliflozin, Metformin, or Combination Therapy in Type 2 Diabetes: Vascular and Molecular Outcomes of a Randomised Controlled Trial.Diabetes, obesity & metabolism · 2026Trial
- Progressive Metabolic Dysregulation from Prediabetes to Diabetes Revealed by Untargeted Metabolomics.International journal of molecular sciences · 2026Article
- Lipid Metabolic Disorders: a Pivotal Driver in Type 2 Diabetes Mellitus Pathogenesis.Current obesity reports · 2026Review
- Lipidomic perspectives on the role of lactosylceramides in inflammation and disease: A narrative review.Expert reviews in molecular medicine · 2026Review
- Ceramides and Type 2 Diabetes: A Scoping Review of Mechanisms, Insulin Resistance, and Nutritional Interventions.Cureus · 2026Review
- Ceramide in Type 2 Diabetes and Obesity: Modulation by Nutrients and Dietary Patterns and Opportunities to Prevent and/or Manage Metabolic-Related Conditions.Metabolites · 2026Review
- Peripheral Insulin Resistance and Alzheimer's Disease: Possible Mediators Including Extracellular Vesicles.Geriatrics & gerontology international · 2026Review
- Untargeted Metabolomics Identifies N-Lactoyl-Amino Acids as Dose-Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- Plasma lipidomics and 15-year risk of incident diabetes: a coronary artery risk development in young adults study.Journal of lipid research · 2026Article
- Multiomics: the intersection of personalized nutrition in cardiometabolic diseases.Journal of translational medicine · 2026Review
- Very long-chain saturated fatty acids in plasma lipids: association with cardiometabolic risk influenced by lipid interactions.Cardiovascular diabetology · 2025Article
- Fingolimod Improves Anxiety-like Behavior and Modulates Sphingosine-1-Phosphate Receptors Gene Expression in a Diabetic Mouse Model.Biomolecules · 2025Article
- Ceramide metabolism and cardiovascular risk factors: insights into therapeutic strategies.Frontiers in cardiovascular medicine · 2025Review
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17 authors.
Funding
Abstract
backgroundType 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk.
methodsCross-sectional relationship between sphingolipid levels, insulin resistance, and T2D prevalence were evaluated in 2,072 American adults from MIDUS cohort. Prospectively, the association between sphingolipid species and the incidence of T2D was analyzed using a case-cohort design nested within the PREDIMED trial (250 cases and a random sample of 692 participants, with 3.8 years of median follow-up). Circulating levels of sphingolipid species in both populations were measured using LC/MS. Hazard ratios were estimated with weighted Cox regression models using Barlow weights.
resultsIn American adults, only CER18:0 and CER22:0 were linked to insulin resistance and a higher prevalence of T2D. Conversely, three lactosylceramides (LCER 14:0, 16:0, and 24:1) showed a strong inverse relationship with both insulin resistance and T2D. These findings led to development of two sphingolipid scores. In the prospective analysis, these scores consistently predicted a reduced risk of T2D incidence in PREDIMED (HR: 0.64, 95% CI 0.44 to 0.94 and 0.58, 0.40 to 0.85 respectively) between extreme quartiles, with 5-year absolute risk differences of 9.6% (95% CI: 0.3-20.5%) and 11.4% (1.0-21.6%). They were validated in the same trial with samples obtained after 1 year of follow-up.
conclusionsOur findings support the potential usefulness of circulating sphingolipid profiles as novel biomarkers for T2D risk. Moreover, this study opens the door for future research on the predictive value and possible protective roles of lactosylceramides in T2D.
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