ArticlePloS one2018
Type 2 diabetes is associated with loss of HDL endothelium protective functions.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Key biomarkers in type 2 diabetes patients: A systematic review.Diabetes, obesity & metabolism · 2025Pooled it
- Impact of different training modalities on high-density lipoprotein function in HFpEF patients: a substudy of the OptimEx trial.ESC heart failure · 2022Trial
- Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.British journal of clinical pharmacology · 2021Trial
- Perimenopausal transdermal estradiol replacement reduces serum HDL cholesterol efflux capacity but improves cardiovascular risk factors.Journal of clinical lipidologyTrial
- Uric acid-to-HDL cholesterol ratio and incident stroke: Competing-risk models in the China Health and Retirement Longitudinal Study.Medicine · 2026Article
- Body roundness index mediates the association between high-density lipoprotein cholesterol and diabetic retinopathy: a population-based cross-sectional study.BMC endocrine disorders · 2026Article
- 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.Journal of clinical medicine · 2026Article
- Relationship between lipid profiles and glycemic control in gestational diabetes mellitus women.BMC pregnancy and childbirth · 2026Article
- Reduced Sphingosine-1-Phosphate Levels Exacerbate Type 2 Diabetes Mellitus and Associated Complications in a High-Fat Diet Mouse Model.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- HDL metabolism and function in diabetes mellitus.Nature reviews. Endocrinology · 2026Review
- Serum PCSK9 is not independently associated with dyslipidaemia in type 2 diabetes: a paired cross-sectional study.Cardiovascular diabetology. Endocrinology reports · 2025Article
- Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes.Cardiovascular diabetology · 2025Observational
- High-Density Lipoprotein in Patients with Diabetic Kidney Disease: Friend or Foe?International journal of molecular sciences · 2025Review
- Increased serum anti-ceramide antibodies and decreased sphingosine-1-phosphate levels in patients with obstructive sleep apnea syndrome as potential markers of endothelial dysfunction.Frontiers in molecular biosciences · 2025Article
- Favourable HDL composition in endurance athletes is not associated with changes in HDL in vitro antioxidant and endothelial anti-inflammatory function.Bioscience reports · 2024Article
- Relationships between HDL subpopulation proteome and HDL function in overweight/obese people with and without coronary heart disease.Atherosclerosis · 2024Article
- High-density lipoprotein in diabetes: Structural and functional relevance.Journal of diabetes investigation · 2024Review
- Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.Neurochemical research · 2024Article
- Circulating Lipoprotein Sphingolipids in Chronic Kidney Disease with and without Diabetes.Biomedicines · 2024Article
- Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisOne of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile.
methodsIn a case-control study (n = 41 per group) nested in the Cooper Center Longitudinal Study we tested the ability of HDL to protect endothelium by stimulating endothelial nitric oxide synthase activity and suppressing NFκB-mediated inflammatory response in endothelial cells. In parallel we measured HDL protein composition, sphinogosine-1-phosphate and P-selectin.
resultsDespite similar levels of plasma HDL-C the HDL in individuals with type 2 diabetes lost almost 40% of its ability to stimulate eNOS activity (P<0.001) and 20% of its ability to suppress TNFα-dependent NFκB-mediated inflammatory response in endothelial cells (P<0.001) compared to non-T2D controls despite similar BMI and lipid profile (HDL-C, LDL-C, TC, TG). Significantly, the ability of HDL to stimulate eNOS activity was negatively associated with plasma levels of P-selectin, an established marker of endothelial dysfunction (r = -0.32, P<0.001). Furthermore, sphingosine-1-phosphate (S1P) levels were decreased in diabetic plasma (P = 0.017) and correlated with HDL-mediated eNOS activation. CONCLUSIONS/INTERPRETATIONS: Collectively, our data suggest that HDL in individuals with type 2 diabetes loses its ability to maintain proper endothelial function independent of HDL-C, perhaps due to loss of S1P, and may contribute to development of diabetic complications.
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