ArticleCardiovascular diabetology2017
Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.
Article in Cardiovascular diabetology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Association Between Metformin and Abdominal Aortic Aneurysm: A Meta-Analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Lipocalin-2 in Intracerebral Hemorrhage: Mechanisms, Biomarker Potential, and Therapeutic Targeting.Neuromolecular medicine · 2026Review
- Changes in Urinary NGAL, FN, and LN Excretion in Type 2 Diabetic Patients Following Anti-Diabetic Therapy with Metformin.Journal of clinical medicine · 2025Article
- The Evolving Role of Neutrophils and Neutrophil Extracellular Traps (NETs) in Obesity and Related Diseases: Recent Insights and Advances.International journal of molecular sciences · 2024Review
- The Role of Fibrinogen in Mediating NGAL-Associated Neuronal Damage in Acute Ischemic Stroke: A Moderated Mediation Analysis.Journal of inflammation research · 2024Article
- Modulatory Role of Autophagy in Metformin Therapeutic Activity toward Doxorubicin-Induced Nephrotoxicity.Toxics · 2023Article
- Multi-arm covariate-adaptive randomization.Science China. Mathematics · 2023Article
- The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism.Nature reviews. Endocrinology · 2022Review
- Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus.Frontiers in medicine · 2022Review
- Serum Lipocalin-2 Levels Are Increased and Independently Associated With Early-Stage Renal Damage and Carotid Atherosclerotic Plaque in Patients With T2DM.Frontiers in endocrinology · 2022Article
- Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next?ACS pharmacology & translational science · 2021Review
- The association of elevated serum lipocalin 2 levels with diabetic peripheral neuropathy in type 2 diabetes.Endocrine connections · 2021Article
- CSF lipocalin-2 increases early in subarachnoid hemorrhage are associated with neuroinflammation and unfavorable outcome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Neutrophil Gelatinase-Associated Lipocalin 2 Accelerates Hypoxia-Induced Endothelial Cell Injury via eNOS/NRF2 Signalling.Cell journal · 2021Article
- The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies.Medicina (Kaunas, Lithuania) · 2021Review
- Lipocalin-2-induced proliferative endoplasmic reticulum stress participates in Kawasaki disease-related pulmonary arterial abnormalities.Science China. Life sciences · 2021Article
- Lipocalin 2 modulates dendritic cell activity and shapes immunity to influenza in a microbiome dependent manner.PLoS pathogens · 2021Article
- NGAL Correlates with Femoral and Carotid Plaque Volume Assessed by Sonographic 3D Plaque Volumetry.Journal of clinical medicine · 2020Article
- Lipocalin-2 exerts pro-atherosclerotic effects as evidenced by in vitro and in vivo experiments.Heart and vessels · 2020Article
- Serum Biomarkers of Cardiovascular Remodelling Reflect Extra-Valvular Cardiac Damage in Patients with Severe Aortic Stenosis.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics.
methodsSerum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens.
resultsSerum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.
conclusionsHigher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.
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