Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Circulating Adhesion Molecules and Oxidative Stress Generation and the Possible Role of Simvastatin Treatment
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Adhesion molecules, particularly intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin, have been associated with cardiovascular disease. Elevated levels of these molecules have been reported in diabetic patients. Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease, and evidence suggests that postprandial hypertriglyceridemia and hyperglycemia may induce an increase in circulating adhesion molecules. However, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate three different meals: a high-fat meal, 75 g of glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, plasma nitrotyrosine, ICAM-1, VCAM-1, and E-selectin were assayed during the tests. Subsequently, diabetic subjects took simvastatin 40 mg/day or placebo for 12 weeks. The three tests were performed again at baseline, between 3 and 6 days after starting the study, and at the end of each study. High-fat load and glucose alone produced an increase of nitrotyrosine, ICAM-1, VCAM-1, and E-selectin plasma levels in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters, but reduced the effect on adhesion molecules and nitrotyrosine, which was observed during every different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations in ICAM-1, VCAM-1, E-selectin, and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on ICAM-1, VCAM-1, and E-selectin plasma levels, suggesting oxidative stress as a common mediator of such effects. Simvastatin shows a beneficial effect on oxidative stress and the plasma levels of adhesion molecules, which may be ascribed to a direct effect in addition to the lipid-lowering action of the drug.
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During postprandial hyperglycemia and hypertriglyceridemia, endothelial dysfunction and inflammation come with a marked rise in nitrotyrosine.
“endothelial dysfunction and inflammation during both postprandial hyperglycemia and hypertriglyceridemia are accompanied by a significant NT increase”
Statins and angiotensin type 1 receptor blockers lower oxidative stress and inflammation and thereby improve endothelial function.
“Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function.”
Earlier work reported that short-term statin therapy can prevent the endothelial dysfunction and oxidative stress caused by hyperglycemia and hypertriglyceridemia.
“In previous studies, the possibility of preventing hyperglycemia-and hypertriglyceridemia-induced endothelial dysfunction and oxidative stress with short-term treatment with statin has been reported.”
Prior studies show that postprandial hyperglycemia and hypertriglyceridemia act independently and cumulatively on endothelial function, with oxidative stress as the shared mediator.
“Indeed, recent studies demonstrate both an independent and a cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, with oxidative stress the common mediator.”
Rising nitrotyrosine levels during hyperglycemia or fat loading support the idea that glucose and free fatty acids trigger oxidative stress through shared pathways.
“The increase in NT, a useful marker of both peroxynitrite and NO activity, during hyperglycemia or fat load supports this hypothesis.[13][14][15]”
Acute hyperglycemia, whether during a hyperglycemic clamp or after a meal, can provoke inflammation to a degree similar to that of postprandial hypertriglyceridemia.
“Furthermore, studies support the evidence that acute hyperglycemia during a hyperglycemic clamp 11 or in the postprandial state 12,13 can induce inflammation as postprandial hypertriglyceridemia.”
In diabetic patients, postprandial hyperglycemia and hypertriglyceridemia each contribute independently and additively to endothelial dysfunction accompanied by oxidative stress and inflammation.
“This study confirms that in diabetic patients both postprandial hyperglycemia and hypertriglyceridemia have an independent and cumulative effect in favoring endothelial dysfunction accompanied by generation of oxidative stress and inflammation.”
In diabetic patients, statins and AT-1 receptor blockers each lower nitrotyrosine production, including during acute rises in blood glucose.
“Statins and AT-1 receptor blockers have been shown singularly to reduce NT generation in diabetic patients, even during an acute increase in glycemia.13,15,17”
A causal relationship has been demonstrated between postprandial hyperglycemia and oxidative stress.
“Thirdly, a causal relationship has been demonstrated between postprandial hyperglycemia and oxidative stress [10]”
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- Authors
- Ceriello, A., Quagliaro, L., Piconi, L., Assaloni, R., Da Ros, R., Maier, A., Esposito, K., & Giugliano, D.
- Affiliations
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Udine, Italy
- University of Udine (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-03-01
- Volume
- 53
- Issue
- 3
- Pages
- 701-710
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2138415287
- Cited by
- 362
- References
- 43
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 4 · 2020: 13 · 2019: 12 · 2018: 8 · 2017: 18 · 2016: 15 · 2015: 17 · 2014: 16 · 2013: 20 · 2012: 23
- FWCI
- 17.57
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- postprandial hypertriglyceridemia, hyperglycemia, adhesion molecules, ICAM-1, VCAM-1, E-selectin, oxidative stress, nitrotyrosine, simvastatin, type 2 diabetes, cardiovascular risk, high-fat meal, glucose tolerance
- MeSH terms
- Hypolipidemic Agents, Diabetes Mellitus, Double-Blind Method, Electrocardiography, Female, Humans, Hyperglycemia, Male, Middle Aged, Triglycerides, Tyrosine, Hypertriglyceridemia, Body Mass Index, Oxidative Stress, Cross-Over Studies, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, E-Selectin, Postprandial Period, Simvastatin, Diabetes Complications
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