HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nappo, F. Articles by Giugliano, D. Search for Related Content PubMed PubMed Citation Articles by Nappo, F. Articles by Giugliano, D.

CLINICAL STUDY: ATHEROSCLEROSIS

Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: Role of fat and carbohydrate meals

Francesco Nappo, MD^*, Katherine Esposito, MD, Michele Cioffi, MD, Giovanni Giugliano^*, Anna Maria Molinari, MD, Giuseppe Paolisso, MD^*, Raffaele Marfella, MD^* and Dario Giugliano, MD^*,*

^* Department of Geriatrics and Metabolic Diseases, Second University of Naples, Naples, Italy
Cardiovascular Research Center, Second University of Naples, Naples, Italy
Department of General Pathology, Chair of Clinical Pathology, Second University of Naples, Naples, Italy

Manuscript received August 10, 2001; revised manuscript received December 18, 2001, accepted January 9, 2002.

^* Reprint requests and correspondence: Dr. Dario Giugliano, Via Emilia 1, 80021 AFRAGOLA (NA), Italy.
dario.giugliano{at}unina2.it

	Abstract

Top Abstract Methods Results Discussion References

 
OBJECTIVES: To compare the effect of a high-fat meal and a high-carbohydrate meal (pizza), with and without antioxidant vitamins, on endothelial activation in healthy subjects and in patients with type 2 diabetes mellitus.

BACKGROUND: The postprandial state is becoming increasingly acknowledged to affect some early events of atherogenesis.

METHODS: In a randomized, observer-blinded, crossover study, 20 newly diagnosed type 2 diabetic patients and 20 age- and gender-matched healthy subjects received two meals at one-week intervals: a high-fat meal (760 calories) and an isoenergetic high-carbohydrate meal (non-cheese pizza). In all subjects, the same meals were repeated immediately following ingestion of vitamin E, 800 IU, and ascorbic acid, 1,000 mg.

RESULTS: In normal subjects, the high-fat meal increased the plasma levels of tumor necrosis factor- (TNF-), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which were prevented by vitamins. No change in these parameters occurred after pizza ingestion or pizza ingestion with vitamins. In diabetic patients, basal concentrations of glucose, cytokines and adhesion molecules were significantly higher than in nondiabetic controls. Both meals significantly increased cytokine and adhesion molecule levels, but the increase was more sustained following the high-fat meal. There was no significant change from baseline when vitamin supplementation accompanied each meal. There was a relationship between changes in serum triglycerides and changes in TNF- (r = 0.39, p < 0.01), IL-6 (r = 0.28, p < 0.05) and VCAM-1 (r = 0.25, p < 0.05), and between changes in plasma glucose and changes in IL-6 (r = 0.36, p < 0.01) and ICAM-1 (r = 0.31, p < 0.02).

CONCLUSIONS: An oxidative mechanism mediates endothelial activation induced by post-meal hyperlipidemia and hyperglycemia.

Abbreviations and Acronyms   ICAM-1   intercellular adhesion molecule-1   IL-6   interleukin-6   TNF-   tumor necrosis factor-alpha   VCAM-1   vascular cell adhesion molecule-1

Increased inflammatory activity is believed to predispose established atherosclerotic plaques to rupture, which can lead to a coronary event (6). In diabetic patients, circulating levels of proinflammatory cytokines (7–9), C-reactive protein (7,8), and soluble adhesion molecules (10–12) are elevated, suggesting stimulation of proatherogenic inflammatory activity. In apparently healthy men and women, chronically high levels of C-reactive protein, interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (ICAM-1) predict increased risk of future cardiovascular events (13–15).

The aim of the present study was to compare the effects of a high-fat meal and a high-carbohydrate meal on plasma concentrations of tumor necrosis factor (TNF)-, IL-6, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) in healthy subjects and in patients with type 2 diabetes mellitus. Because an oxidative mechanism seems to be implicated in endothelial dysfunction after a high-fat meal (16,17), we also investigated whether acutely induced changes in circulating levels of cytokines and adhesion molecules were influenced by administration of antioxidant vitamin supplements.

	Methods

Top Abstract Methods Results Discussion References

 
Twenty healthy subjects were recruited from the medical and paramedical staff of the Department of Geriatrics and Metabolic Diseases at the Second University of Naples. They had no evidence of present or past hypertension, hyperlipidemia, diabetes or any systemic conditions. All subjects were following ad libitum diets, had no recent change in body weight or intercurrent illness and were taking no medication. Particular care was taken to ensure subjects had not recently used supplemental vitamins. None smoked. Twenty patients with newly diagnosed (within six months of diagnosis) type 2 diabetes mellitus were recruited from the Diabetes Clinic at the teaching hospital of the Second University of Naples. Exclusion criteria included presence of hepatic or renal disease; diabetic complications, both microvascular and macrovascular; cigarette smoking; hypertension; use of dietary antioxidant supplements; and treatment with lipid-lowering drugs. All patients were treated only by diet and were instructed not to change their usual dietary habits for the duration of the study. The protocol of the study was approved by the ethics committee of the Second University of Naples; healthy subjects and diabetic patients volunteered (without being paid) for the study and gave informed written consent before being tested. The clinical characteristics of the study populations are reported in Table 1.

Subjects were allowed to walk or sit, as they wished, during the interval between the first and second assessments. Blood was collected with minimal stasis by vein-puncture after a brief rest in a supine position. Parameters were analyzed by independent investigators performing laboratory assays and blinded to the subject’s identity, meal status and temporal sequence. Plasma was separated by centrifugation and stored at –80°C until analysis. Assays for serum total and high-density lipoprotein cholesterol, triglyceride, and glucose levels were performed in the hospital’s chemistry laboratory. Plasma concentrations of TNF-, IL-6, ICAM-1 and VCAM-1 were measured in duplicate using an enzyme-linked immunosorbent assay (R & D Systems, Minneapolis, Minnesota). All samples for a given subject were analyzed in the same series. The intra- and interassay coefficients of variation for the immunosorbent assays were below 5%.

Results are given as mean ± SD. Sample size was determined on the basis of two preliminary experiments with a high-fat meal, two with a pizza meal and two with a high-fat meal and vitamins. These experiments allowed us to estimate the SD and the difference between the means. For a desired p value of 0.05 and 80% power to detect an actual difference, a sample size of 10 per group was considered satisfactory (18). The statistical significance of differences between the experimental groups was determined by one-way analysis of variance (ANOVA). Scheffé’s test method was used as a post hoc test if any differences were noted with ANOVA. The effect of order was tested with the analysis of variance. Linear regression analysis was used as appropriate. A p value of <0.05 was considered statistically significant.

	Results

Top Abstract Methods Results Discussion References

 
Nondiabetic subjects.   Lipid, glucose, blood pressure, cytokine and adhesion molecule parameters were similar in each of the study days, and there was no evidence of an order effect. Following the ingestion of the high-fat meal, mean serum triglyceride levels increased from 0.9 ± 0.2 to 1.2 ± 0.3 mmol/l at 4 h (p = 0.009). A similar increase was seen 4 h after the high-fat meal with vitamins (p = 0.008), whereas no increase in plasma triglyceride levels occurred after the pizza meal (Fig. 1). No significant change in glucose levels was observed after the meals. Plasma levels of TNF- (p = 0.009), IL-6 (p = 0.01), ICAM-1 (p = 0.011) and VCAM-1 (p = 0.01) rose significantly after the high-fat meal, but not the pizza meal (Figs. 2 and 3); when vitamin supplementation accompanied the high-fat meal, there was a significant reduction of the rise of cytokine (TNF-, p = 0.04; IL-6, p = 0.045) and adhesion molecule parameters (ICAM-1 p = 0.03, VCAM-1 p = 0.035) with values not significantly different from baseline (Table 2). There was a significant correlation between changes in serum triglyceride levels after the high-fat meal and changes in TNF- (r = 0.23, p < 0.05).

View larger version (24K): [in this window] [in a new window]   Figure 1 Changes in circulating glucose and triglyceride levels following high-fat and high-carbohydrate (pizza) meals in normal subjects and in patients with type 2 diabetes mellitus.

View larger version (11K): [in this window] [in a new window]   Figure 2 Effects of a high-fat meal on plasma concentrations of proinflammatory cytokines (TNF-, IL-6) and adhesion molecules (ICAM-1, VCAM-1) in healthy subjects (open circles) and diabetic patients (filled circles). ICAM-1 = intercellular adhesion molecule-1; IL-6 = interleukin-6; TNF- = tumor necrosis factor-; VCAM-1 = vascular cell adhesion molecule-1.

View larger version (12K): [in this window] [in a new window]   Figure 3 Effects of a high-carbohydrate meal (non-cheese pizza) on plasma concentrations of proinflammatory cytokines (TNF-, IL-6) and adhesion molecules (ICAM-1, VCAM-1) in healthy subjects (open circles) and diabetic patients (filled circles). ICAM-1 = intercellular adhesion molecule-1; IL-6 = interleukin-6; TNF- = tumor necrosis factor-; VCAM-1 = vascular cell adhesion molecule-1.

Triglyceride, glucose, cytokine and adhesion molecule parameters were similar in each of the study days and there was no evidence of an order effect. The rise in serum triglyceride levels in the diabetic patients was significantly greater (p = 0.009) than that recorded in nondiabetic subjects following the same meals (Fig. 1).

Mean plasma glucose rose from a basal value of 9.1 ± 0.8 to 11.8 ± 1.1 mmol/l (p = 0.01) 2 h after the high-fat meal and returned to below baseline at 4 h (Fig. 1). Following the pizza meal, the rise in plasma glucose levels was more sustained and lasted longer (p = 0.008 vs. baseline, p = 0.02 vs. high-fat). The rise in serum triglyceride and plasma glucose levels following the high-fat meal and pizza meal with vitamins were not significantly different (p = 0.53, p = 0.47, respectively) from the meals ingested without vitamins (Table 2).

Following the ingestion of high-fat meal, mean plasma concentrations of TNF- (p = 0.008), IL-6 (p = 0.009), ICAM-1 (p = 0.008) and VCAM-1 (p = 0.007) rose steadily, reaching a plateau at 4 h (Fig. 2). These elevations from basal values were significantly higher than those recorded in nondiabetic subjects after the same high-fat meal (p = 0.01, p = 0.016, p = 0.026, p = 0.016, respectively). Moreover, the increase in plasma cytokine and adhesion molecule levels following the high-fat meal was also greater than that obtained after the pizza meal (p = 0.025, p = 0.036, p = 0.016, p = 0.026, respectively) (Fig. 3). When vitamin supplementation accompanied the high-fat or pizza meal, there was a significant reduction of the rise of cytokine and adhesion molecule parameters, with values that were significantly lower as compared with those recorded following the meals without vitamins (TNF-, p = 0.025; IL-6, p = 0.035; ICAM-1, p = 0.016; VCAM-1, p = 0.04) and not significantly different from baseline (Table 2).

There was a significant correlation between changes in serum triglyceride levels following the high-fat meal and changes in TNF- (r = 0.39, p < 0.01), IL-6 (r = 0.28, p < 0.05), and VCAM-1 (r = 0.25, p < 0.05). Moreover, there was also a correlation between changes in plasma glucose levels following the pizza meal and changes in IL-6 (r = 0.36, p < 0.01), and ICAM-1 (r = 0.31, p < 0.02).

	Discussion

Top Abstract Methods Results Discussion References

 
We found that a single high-fat meal acutely affects the level of markers of cardiovascular risk in normolipidemic healthy subjects. To our knowledge, this is the first demonstration that a fat-enriched meal, in contrast to a high-carbohydrate meal, is associated with endothelial activation, as indicated by the increased circulating levels of the adhesion molecules ICAM-1 and VCAM-1.

Foodstuffs and endothelial activation.   Soluble forms of cellular adhesion found in plasma are considered an index of endothelial activation and even a molecular marker of early atherosclerosis (15). The term endothelial activation describes the functional changes that endothelia may undergo under the influence of various stimuli, the best studied of which are inflammatory cytokines and bacterial endotoxin (19). In this context, the increase of circulating levels of TNF- and IL-6 following the high-fat meal might have induced endothelial activation and upregulation of adhesion molecule expression. Tumor necrosis factor- functions within a complex and tightly regulated cytokine network activating multiple signal transduction pathways and inducing or suppressing a wide variety of genes, including those encoding for other cytokines and adhesion molecules (20).

Postprandial lipidemia is strongly associated with a risk of development of atherosclerotic lesions (21). It is noteworthy that IL-6 may induce endothelial expression of chemokines and adhesion molecules (22), and its plasma concentrations are predictive of future myocardial infarction among apparently healthy men (14). Thus, postprandial hypertriglyceridemia may be the link between high-fat meal and endothelial activation in normal subjects.

Unlike the high-fat meal, the pizza meal does not activate endothelium in normal subjects. Although acute and postprandial hyperglycemia are increasingly being seen as toxic for endothelial functions (23,24), the glycemic excursions following the pizza meal in normal subjects were very small and had returned to basal levels at the time of testing. This did not happen in type 2 diabetic patients in whom plasma glucose levels remained elevated 4 h after ingestion of the pizza meal. In this condition, circulating levels of cytokines and adhesion molecules were significantly elevated above baseline, with a direct relationship with blood glucose levels. Moreover, the diabetic patients who ate the high-fat meal presented with the greatest endothelial activation, as indicated by the highest circulating levels of TNF-, IL-6, ICAM-1 and VCAM-1.

The diabetic patients herein studied presented endothelial activation in the basal state as indicated by the circulating cytokine and adhesion molecule levels, which were significantly higher than those of age-matched nondiabetic subjects. This is consistent with current evidence indicating that in diabetic patients circulating levels of some proinflammatory cytokines (7–9), C-reactive protein (7,8), and soluble adhesion molecules, such as ICAM-1 (10,11) and VCAM-1 (11,25), are significantly higher compared with the nondiabetic population. Because increased inflammation activity is believed to predispose established atherosclerotic plaques to rupture, endothelial activation occurring in diabetes may help explain why type 2 diabetic patients are at increased risk of developing coronary heart disease compared with the general population (26).

The effect of antioxidant vitamins.   Impairment of endothelium-dependent vasodilation following a high-fat meal has previously been reported (16,17) and attributed to an oxidative mechanism. In our study, pretreatment with antioxidant vitamin supplements normalized endothelial activation following the high-fat meal in normal subjects and strongly reduced circulating levels of cytokine and adhesion molecules in diabetic patients following high-fat or pizza meals. Supplementation with high doses of vitamin E markedly reduces susceptibility of isolated LDL to oxidation and inhibits secretion of proinflammatory cytokines (27). Our data seem to indicate that an oxidative mechanism mediates the effect of a high-fat meal on cytokine and adhesion molecule levels; this hypothesis is strengthened by the evidence that another structurally unrelated antioxidant, such as glutathione, prevents the increased plasma ICAM-1 levels seen after postprandial hyperglycemia in humans (28).

Study limitations.   Although the present study utilized familiar foodstuffs rather than laboratory diet, it did not attempt to differentiate the effect of single nutrient in the meals, or to determine the healthiest mixture of foods for the endothelium. However, diets consumed by individuals consist of a combination of foods containing multiple nutrients and non-nutrients. Moreover, an attempt was not made to differentiate the effects of vitamin C and vitamin E. Finally, this study was based on surrogate end points.

Conclusions.   The results from this study indicate that a high-fat meal in healthy subjects is able to switch the endothelium towards a more atherogenetic profile, which is amplified in patients with type 2 diabetes mellitus. The pizza meal causes endothelial activation in diabetic subjects only, although to a lesser extent than the high-fat meal does. Endothelial activation is prevented by antioxidant vitamins, suggesting an oxidative mechanism mediated by post-meal hyperlipidemia and hyperglycemia. The lack of endothelial activation after the pizza meal, at least in nondiabetic subjects, may contribute to the healthier cardiovascular outlook of people consuming a Mediterranean-type diet (29,30).

	Footnotes

 
This study was supported by a research grant from the Second University of Naples.

	References

Top Abstract Methods Results Discussion References

 

1. Tribble DE. Antioxidant consumption and risk of coronary heart disease: emphasis on vitamin C, vitamin E, and beta-carotene. Circulation. 1999;99:591–595[Free Full Text]
2. Vershuren WMM, Jacobs DR, Bloemberg BPM, et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures. JAMA. 1995;274:131–136[Abstract]
3. Kant AK, Schatzkin A, Graubard BR, et al. A prospective study of diet quality and mortality in women. JAMA. 2000;283:2109–2115[Abstract/Free Full Text]
4. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79:350–354[CrossRef][Medline]
5. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899–1906[Abstract/Free Full Text]
6. Moreno PR, Falk E, Palacios IF, et al. Macrophage infiltration in acute coronary syndromes: implications for plaque rupture. Circulation. 1994;90:775–778[Abstract/Free Full Text]
7. Pickup JC, Mattock MB, Chusney GD, et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia. 1997;40:1286–1292[CrossRef][Medline]
8. Arnalich F, Hernanz A, Lopez-Maderuelo D, et al. Enhanced acute-phase response and oxidative stress in older adults with type II diabetes. Horm Metab Res. 2000;32:407–412[Medline]
9. Pickup JC, Chusney GD, Thomas SM, et al. Plasma interleukin-6, tumor necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci. 2000;67:291–300[CrossRef][Medline]
10. Ceriello A, Falleti E, Motz E, et al. Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus: the possible role of oxidative stress. Horm Metab Res. 1998;30:146–149[Medline]
11. Marfella R, Esposito K, Giunta R, et al. Circulating adhesion molecules in humans. Role of hyperglycemia and hyperinsulinemia. Circulation. 2000;101:2247–2251[Abstract/Free Full Text]
12. Ryysy L, Yki-Jarvinen H. Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes. Diabetes Care. 2001;24:549–554[Abstract/Free Full Text]
13. Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation. 1999;100:1148–1150[Free Full Text]
14. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101:1767–1772[Abstract/Free Full Text]
15. Ridker PM, Hennekens CH, Roitman-Johnson P, et al. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998;351:88–92[CrossRef][Medline]
16. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA. 1997;278:1682–1686[Abstract]
17. Williams MJA, Sutherland WHF, McCormick MP, et al. Impaired endothelial function following a meal rich in used cooking fat. J Am Coll Cardiol. 1999;33:1050–1055[Abstract/Free Full Text]
18. Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatics. Norwalk, CT: Appleton & Lange; 1990.
19. De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr. 2000;71(Suppl 1):213S–223S[Abstract/Free Full Text]
20. Bellisarii FL, Gallina S, De Caterina R. Tumor necrosis factor-alpha and cardiovascular disease. Ital Heart J. 2001;2:408–417[Medline]
21. Ebenbichler CF, Kirchmair R, Egger C, et al. Postprandial state and atherosclerosis. Curr Opin Lipidol. 1995;6:286–290[Medline]
22. Romano M, Sironi M, Toniatti C, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6:315–325[CrossRef][Medline]
23. Giugliano D, Marfella R, Coppola L, et al. Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation. 1997;95:1783–1790[Abstract/Free Full Text]
24. Giugliano D, Ceriello A. The toxic trio: acute, chronic, and post-prandial hyperglycaemia. Nutr Metab Cardiovasc Dis. 2001;11:80–83[Medline]
25. Steiner M, Reihardt KM, Krammer B, et al. Increased levels of soluble adhesion molecules in type 2 (non insulin dependent) diabetes mellitus are independent of glycaemic control. Thromb Haemost. 1994;72:979–984[Medline]
26. Bierman EL. Atherogenesis in diabetes. Arterioscler Thromb. 1992;12:647–656[Free Full Text]
27. Devaraj S, Jialal I. The effect of alpha-tocopherol on critical cells in atherogenesis. Curr Opin Lipidol. 1998;9:11–15[CrossRef][Medline]
28. Ceriello A, Bortolotti N, Motz E, et al. Meal-generated oxidative stress in type 2 diabetic patients. Diabetes Care. 1998;21:1529–1534[Abstract]
29. Keys A. Mediterranean diet and public health: personal reflections. Am J Clin Nutr. 1995;61:51321–51323
30. Robertson RM, Smaha L. Can a Mediterranean-style diet reduce heart disease? Circulation. 2001;103:1821[Free Full Text]

This article has been cited by other articles:

				S. E. E. Berry, S. Tucker, R. Banerji, B. Jiang, P. J. Chowienczyk, S. M. Charles, and T. A. B. Sanders Impaired Postprandial Endothelial Function Depends on the Type of Fat Consumed by Healthy Men J. Nutr., October 1, 2008; 138(10): 1910 - 1914. [Abstract] [Full Text] [PDF]

				W. L. Hall, K. A. Sanders, T. A. B. Sanders, and P. J. Chowienczyk A High-Fat Meal Enriched with Eicosapentaenoic Acid Reduces Postprandial Arterial Stiffness Measured by Digital Volume Pulse Analysis in Healthy Men J. Nutr., February 1, 2008; 138(2): 287 - 291. [Abstract] [Full Text] [PDF]

				R. Peter and A. Rees Review: Postprandial glycaemia and cardiovascular risk The British Journal of Diabetes & Vascular Disease, January 1, 2008; 8(1): 8 - 14. [Abstract] [PDF]

				J. Plat, A. Jellema, J. Ramakers, and R. P. Mensink Weight Loss, but Not Fish Oil Consumption, Improves Fasting and Postprandial Serum Lipids, Markers of Endothelial Function, and Inflammatory Signatures in Moderately Obese Men J. Nutr., December 1, 2007; 137(12): 2635 - 2640. [Abstract] [Full Text] [PDF]

				C. Erridge, T. Attina, C. M Spickett, and D. J Webb A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1286 - 1292. [Abstract] [Full Text] [PDF]

				T. Mita, H. Watada, T. Shimizu, Y. Tamura, F. Sato, T. Watanabe, J. B. Choi, T. Hirose, Y. Tanaka, and R. Kawamori Nateglinide Reduces Carotid Intima-Media Thickening in Type 2 Diabetic Patients Under Good Glycemic Control Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2456 - 2462. [Abstract] [Full Text] [PDF]

				D. H St-Pierre, J.-P. Bastard, L. Coderre, M. Brochu, A. D Karelis, M.-E. Lavoie, F. Malita, J. Fontaine, D. Mignault, K. Cianflone, et al. Association of acylated ghrelin profiles with chronic inflammatory markers in overweight and obese postmenopausal women: a MONET study Eur. J. Endocrinol., October 1, 2007; 157(4): 419 - 426. [Abstract] [Full Text] [PDF]

				P. H. McNulty, M. A. Tulli, B. J. Robertson, V. Lendel, L. A. Harach, S. Scott, and J. P. Boehmer Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H103 - H108. [Abstract] [Full Text] [PDF]

				F. Mariotti, J. F. Huneau, I. Szezepanski, K. J. Petzke, Y. Aggoun, D. Tome, and D. Bonnet Meal Amino Acids with Varied Levels of Arginine do Not Affect Postprandial Vascular Endothelial Function in Healthy Young Men J. Nutr., June 1, 2007; 137(6): 1383 - 1389. [Abstract] [Full Text] [PDF]

				M. E. Tushuizen, R. Nieuwland, C. Rustemeijer, B. E. Hensgens, A. Sturk, R. J. Heine, and M. Diamant Elevated Endothelial Microparticles Following Consecutive Meals Are Associated With Vascular Endothelial Dysfunction in Type 2 Diabetes Diabetes Care, March 1, 2007; 30(3): 728 - 730. [Full Text] [PDF]

				L. J. Ignarro, M. L. Balestrieri, and C. Napoli Nutrition, physical activity, and cardiovascular disease: An update Cardiovasc Res, January 15, 2007; 73(2): 326 - 340. [Abstract] [Full Text] [PDF]

				D. Giugliano, A. Ceriello, and K. Esposito The Effects of Diet on Inflammation: Emphasis on the Metabolic Syndrome J. Am. Coll. Cardiol., August 15, 2006; 48(4): 677 - 685. [Abstract] [Full Text] [PDF]

				D. Giugliano and K. Esposito Virgin Olive Oil and Vegetables Improve Endothelial Health J. Am. Coll. Cardiol., July 18, 2006; 48(2): 413 - 414. [Full Text] [PDF]

				M. Maggio, J. M. Guralnik, D. L. Longo, and L. Ferrucci Interleukin-6 in aging and chronic disease: a magnificent pathway. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 575 - 584. [Abstract] [Full Text] [PDF]

				A. Basu, S. Devaraj, and I. Jialal Dietary Factors That Promote or Retard Inflammation Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 995 - 1001. [Abstract] [Full Text] [PDF]

				M. Shimabukuro, N. Higa, I. Chinen, K. Yamakawa, and N. Takasu Effects of a Single Administration of Acarbose on Postprandial Glucose Excursion and Endothelial Dysfunction in Type 2 Diabetic Patients: A Randomized Crossover Study J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 837 - 842. [Abstract] [Full Text] [PDF]

				K. Esposito and D. Giugliano Diet and inflammation: a link to metabolic and cardiovascular diseases Eur. Heart J., January 1, 2006; 27(1): 15 - 20. [Abstract] [Full Text] [PDF]

				N. Ahmed, R. Babaei-Jadidi, S. K. Howell, P. J. Thornalley, and P. J. Beisswenger Glycated and Oxidized Protein Degradation Products Are Indicators of Fasting and Postprandial Hyperglycemia in Diabetes Diabetes Care, October 1, 2005; 28(10): 2465 - 2471. [Abstract] [Full Text] [PDF]

				E. Corpeleijn, W. H. M. Saris, E. H. J. M. Jansen, P. M. H. J. Roekaerts, E. J. M. Feskens, and E. E. Blaak Postprandial Interleukin-6 Release from Skeletal Muscle in Men with Impaired Glucose Tolerance Can Be Reduced by Weight Loss J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5819 - 5824. [Abstract] [Full Text] [PDF]

				D. Giugliano, R. Marfella, K. Esposito, A. C. Ferreira, A. A. Peter, J. A. Chirinos, R. Ghany, S. Virani, S. Garcia, J. Purow, et al. Letter Regarding Article by Ferriera et al, "Postprandial Hypertriglyceridemia Increases Circulating Levels of Endothelial Cell Microparticles" * Response Circulation, June 28, 2005; 111(25): e457 - e458. [Full Text] [PDF]

				A. Ceriello, R. Assaloni, R. Da Ros, A. Maier, L. Piconi, L. Quagliaro, K. Esposito, and D. Giugliano Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients Circulation, May 17, 2005; 111(19): 2518 - 2524. [Abstract] [Full Text] [PDF]

				P. A. Tataranni and E. Ortega A Burning Question: Does an Adipokine-Induced Activation of the Immune System Mediate the Effect of Overnutrition on Type 2 Diabetes? Diabetes, April 1, 2005; 54(4): 917 - 927. [Abstract] [Full Text] [PDF]

				M. R. Skilton, N. T. Lai, K. A. Griffiths, L. M. Molyneaux, D. K. Yue, D. R. Sullivan, and D. S. Celermajer Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1404 - H1410. [Abstract] [Full Text] [PDF]

				A. Ceriello Postprandial Hyperglycemia and Diabetes Complications: Is It Time to Treat? Diabetes, January 1, 2005; 54(1): 1 - 7. [Abstract] [Full Text] [PDF]

				P. A. Economides, L. Khaodhiar, A. Caselli, A. E. Caballero, H. Keenan, S.-E. Bursell, G. L. King, M. T. Johnstone, E. S. Horton, and A. Veves The Effect of Vitamin E on Endothelial Function of Micro- and Macrocirculation and Left Ventricular Function in Type 1 and Type 2 Diabetic Patients Diabetes, January 1, 2005; 54(1): 204 - 211. [Abstract] [Full Text] [PDF]

				M E Tushuizen, M Diamant, and R J Heine Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes Postgrad. Med. J., January 1, 2005; 81(951): 1 - 6. [Abstract] [Full Text] [PDF]

				J. M.R. Gill, A. Al-Mamari, W. R. Ferrell, S. J. Cleland, C. J. Packard, N. Sattar, J. R. Petrie, and M. J. Caslake Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men J. Am. Coll. Cardiol., December 21, 2004; 44(12): 2375 - 2382. [Abstract] [Full Text] [PDF]

				P. J. Manning, W. H. Sutherland, G. Hendry, S. A. de Jong, M. McGrath, and S. M. Williams Changes in Circulating Postprandial Proinflammatory Cytokine Concentrations in Diet-Controlled Type 2 Diabetes and the Effect of Ingested Fat Diabetes Care, October 1, 2004; 27(10): 2509 - 2511. [Full Text] [PDF]

				K. Esposito, R. Marfella, M. Ciotola, C. Di Palo, F. Giugliano, G. Giugliano, M. D'Armiento, F. D'Andrea, and D. Giugliano Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome: A Randomized Trial JAMA, September 22, 2004; 292(12): 1440 - 1446. [Abstract] [Full Text] [PDF]

				S. P. Zhao, L. Liu, Y. C. Cheng, M. H. Shishehbor, M. H. Liu, D. Q. Peng, and Y. L. Li Xuezhikang, an Extract of Cholestin, Protects Endothelial Function Through Antiinflammatory and Lipid-Lowering Mechanisms in Patients With Coronary Heart Disease Circulation, August 24, 2004; 110(8): 915 - 920. [Abstract] [Full Text] [PDF]

				K. Esposito, D. Giugliano, F. Nappo, R. Marfella, and for the Campanian Postprandial Hyperglycemia Study Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in Type 2 Diabetes Mellitus Circulation, July 13, 2004; 110(2): 214 - 219. [Abstract] [Full Text] [PDF]

				A. Ceriello and E. Motz Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited Arterioscler. Thromb. Vasc. Biol., May 1, 2004; 24(5): 816 - 823. [Abstract] [Full Text]

A. Ceriello, L. Quagliaro, L. Piconi, R. Assaloni, R. Da Ros, A. Maier, K. Esposito, and D. Giugliano Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Circulating Adhesion Molecules and Oxidative Stress Generation and the Possible Role of Simvastatin Treatment Diabetes, March 1, 2004; 53(3): 701 - 710. [Abstract] [Full Text] [PDF]