European Heart Journal

European Heart Journal Advance Access originally published online on October 11, 2005
European Heart Journal 2006 27(1):15-20; doi:10.1093/eurheartj/ehi605

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Diet and inflammation: a link to metabolic and cardiovascular diseases

Katherine Esposito and Dario Giugliano^*

Division of Metabolic Diseases, Policlinico Seconda Università di Napoli, University of Naples, Piazza L. Miraglia, 80138 Naples, Italy

Received 30 May 2005; revised 21 September 2005; accepted 29 September 2005; online publish-ahead-of-print 11 October 2005.

^* Corresponding author. Fax: +39 081 5665054 E-mail address: dario.giugliano{at}unina2.it

See page 13 for the editorial comment on this article (doi:10.1093/eurheartj/ehi638)

	Abstract

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Both epidemiological studies and intervention trials support an important role of diet in reducing the risk of a variety of chronic diseases, including cardiovascular disease, and overall mortality. We discuss available evidence indicating that the generation of a pro-inflammatory milieu might be one mechanism through which unhealthy diets are linked to metabolic and cardiovascular diseases. In practical terms, fully understanding the link between diet and inflammation holds the premise to elucidate the mechanisms by which dietary patterns improve cardiovascular health.

Key Words: Dietary patterns • Inflammation • Endothelial dysfunction • Insulin resistance • Metabolic syndrome

Modern society has brought with it profound changes in lifestyle and an increased incidence of atherosclerotic vascular disease. Body weights are on the rise, diets are becoming less healthy, and people are becoming increasingly sedentary, resulting in metabolic alterations that increase atherothrombotic risk. Not surprisingly, obesity, the metabolic syndrome, and type 2 diabetes mellitus are becoming a public health problem of epidemic proportions.¹ Nearly 70% of type 2 diabetes risk in the US is attributable to overweight and obesity.²

In the past two decades, understanding of the nutrients and foods likely to promote cardiac health has grown substantially owing to studies of the molecular mechanisms of atherosclerosis and the metabolic effects of various nutrients and foods. Dietary patterns that emphasize whole grain foods and legumes, and vegetables and fruits, and that limit red meat, full-fat dairy products, and food and beverages high in added sugars are associated with decreased risk of a variety of chronic disease.³ In a more general sense, adherence to healthy lifestyle practices, which of course also include healthy diets, has been found to be associated with an 83% reduction in the rate of coronary disease, a 91% reduction in diabetes in women, and a 71% reduction in colon cancer in men.⁴ Despite this mounting evidence, ‘Western’ diets have shifted unfavourably. Vegetable and fruit consumption of both adults and youth continues to be below recommended levels: only 24.5% of adults and 21.4% of youth consume at least five servings each day, whereas consumption of refined grains and food high in added sugars are on the rise. Low consumption of fruit and vegetables, together with physical inactivity, are now among the top 10 causes of mortality in developed countries.⁵

We review available evidence indicating that the generation of a pro-inflammatory milieu might be one mechanism through which unhealthy diets are linked to metabolic and cardiovascular diseases. Relevant peer-reviewed publications pertinent to the topic covered by the present review were identified by content experts; priority was given to the English language, epidemiological and clinical trials, time and venue of publication, and relevance to clinicians.

	Post-prandial state

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Much attention has been paid to the evidence that abnormalities of the post-prandial state are important contributing factors to the development of atherosclerosis. Post-prandial hypertriglyceridaemia has been shown to be a risk factor for cardiovascular disease in non-diabetic subjects and may be a predictor of carotid intima-media thickness in type 2 diabetic patients.⁶ Moreover, clinical data also suggest that post-prandial hyperglycaemia is a risk factor for cardiovascular disease.⁷ Meal absorption is a complex phenomenon, and post-prandial hyperlipidaemia and hyperglycaemia are simultaneously present in the post-absorptive phase, particularly in diabetic patients or in subjects with impaired glucose tolerance. Both post-prandial hyperglycaemia and hypertriglyceridaemia may cause endothelial dysfunction, which is considered an early marker of atherosclerosis. Evaluating the effect of different isocaloric meals on endothelial function in both normal subjects and type 2 diabetic patients, we have shown that the level of triglycerides after a high-fat (saturated) meal is inversely associated with endothelial function, with maximal impairment occurring at the time of the simultaneous presence of post-prandial hyperglycaemia and hypertriglyceridaemia.⁸ Similar conclusions were reached by other studies investigating the effect of liquid meals rich in carbohydrates or saturated fats.^9,10 Moreover, endothelial dysfunction induced by a high-fat meal in type 2 diabetic patients¹¹ or associated with fasting hypertriglyceridaemia in young men¹² is also associated with increased plasma concentrations of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor suggested as a novel cardiovascular risk factor.¹³

Not all macronutrients are the same and some of them may show opposite effects. For instance, consumption of a high-fat meal together with vegetable foods rich in natural antioxidants largely prevents the negative effects on endothelial function.¹⁴ In particular, endothelial dysfunction acutely triggered by the consumption of a high-fat meal rich in saturated fatty acids is reduced by the simultaneous consumption of a vegetable serving including pepper (100 g), tomatoes (100 g), and carrots (200 g).

A mild pro-oxidative state accompanies meal ingestion, which results in raised circulating biomarkers of inflammation, adhesion, and endothelial dysfunction, all of which are factors in the development of cardiovascular disease.¹⁵ The effect of hyperglicaemia, hypertriglyceridaemia, and raised free fatty acids (FFA) levels, both fasting and post-prandial, on endothelial function may be mediated through the generation of an oxidative stress. The process is supposed to involve increased superoxide generation, which in turn inactivates nitric oxide. Superoxide and nitric oxide combine to produce peroxynitrite, a potent and long-lived oxidant that is cytotoxic, initiates lipid peroxidation, and nitrates amino acids such as tyrosine, which affects many signal transduction pathways. The production of the peroxynitrite anion can be indirectly inferred by the presence of nitrotyrosine (NT). An increase in plasma NT levels has been reported in association with post-prandial hyperglycaemia or hypertriglycidaemia, with a cumulative effect occurring in the presence of both conditions.⁹ Hence, oxidative stress may be a mediator of the effect of raised substrate concentration in the post-prandial phase.¹⁶

It can be presumed that what happens during the absorption phase is of considerable importance, because it occurs several times every day, and human beings now spend an increasingly greater part of their lives in the post-prandial phase.

	Macronutrients generates inflammation

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Macronutrient intake may produce oxidative stress and inflammatory responses. Glucose ingestion in normal subjects is associated with increased superoxide generation in leukocytes and mononuclear cells, as well as with raised amount and activity of nuclear factor-B (NF-B), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory.¹⁷ Glucose ingestion also causes an increase in two other pro-inflammatory transcription factors, activating protein-1 (AP-1) and Egr-1, the first regulating the transcription of matrix metalloproteinases and the second modulating the transcription of tissue factor and plasminogen activator inhibitor-1. A mixed meal from a fast-food chain has also been shown to induce activation of NF-B associated with the generation of reactive oxygen species (ROS) by mononuclear cells. Interestingly enough, superoxide is an activator of at least two major pro-inflammatory transcription factors, NF-B and AP-1. These findings are in line with previous studies demonstrating that after oral or intravenous glucose challenges, in both normal subjects and patients with type 2 diabetes mellitus, there is an increased generation of ROS and raised circulating levels of inflammatory cytokines, such as tumour necrosis factor- (TNF-), interleukin 6 (IL-6), and interleukin 18 (IL-18).^9,18,19

A single high-fat meal in normal subjects produces endothelial activation, as evidenced by increased concentrations of the adhesion molecules VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1), in association with raised plasma concentrations of IL-6 and TNF-.⁸ Moreover, the same high-fat meal²⁰ may increase the circulating levels of IL-18, a pro-inflammatory cytokine supposed to be involved in plaque destabilization, associated with the simultaneous decrease of circulating adiponectin, an adipocyte-derived protein with insulin sensitizing, anti-inflammatory, and antiatherogenic properties.²¹

	From dietary inflammation to insulin resistance

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Ingestion of particular macronutrients causes a shift towards oxidative stress and inflammation, which in turn may reduce insulin sensitivity. Metabolic abnormalities found in diabetes, obesity, and the metabolic syndrome include, among others, increases in the circulating levels of metabolites, such as FFA and triglycerides, and cytokines, such as TNF- and IL-6. Both FFA and inflammatory markers have been shown to predict type 2 diabetes independent of known risk factors.^22,23 Both FFA and TNF- have also been shown to activate inhibitor K kinase ß (IKKß) in adipocytes and hepatocytes, which can then increase the serine phosphorylation of insulin receptor substrate 1 (IRS-1), with subsequent reduction in insulin-dependent tyrosine phosphorylation of IRS-1, and ultimately glucose transport.²⁴ IKKß is a serine kinase that controls the activation of NF-B, a transcription factor associated with inflammation. IRS-1 may be directly phosphorylated by IKKß at serine residues, representing a novel class of substrates for IKKß.²⁵ Convincing evidence for this has come from a recent study²⁶ in which hepatic expression of the IkappaBalpha super-repressor, which reduces IKKß activity, reversed the phenotype of wild-type mice fed a high-fat diet, indicating that lipid accumulation in the liver leads to subacute hepatic ‘inflammation’ through NF-B activation and downstream cytokine production. This causes insulin resistance both locally in liver and systemically.

IL-6 circulates in plasma at high concentrations and is associated with insulin resistance in men and in obese or hyperandrogenic women.²⁷ Circulating IL-6 levels and insulin sensitivity relationships seem to occur in parallel to increases in plasma FFA. In contrast to IL-6 and TNF-, adiponectin mRNA is reduced in adipose tissue from patients with type 2 diabetes.²¹ Although the precise mechanism by which a low adiponectin production contributes to insulin resistance has not been fully elucidated, there is evidence that adiponectin decreases circulating FFA levels by increasing fatty acid oxidation by skeletal muscle.²⁸ An unbalance between inflammatory and anti-inflammatory cytokines may contribute to the enhancement of the endogenous pro-inflammatory potential in the post-prandial phase, particularly following the ingestion of ‘Western’ dietary patterns. Part of this effect may be mediated through modification of circulating FFA levels.

Resistance to the anti-inflammatory actions of insulin might also play a role. At physiologically relevant concentrations, insulin causes a suppression of NF-B, thus reducing the production of some of its transcripts, namely IL-6 and TNF-.²⁹ This effect has been related to the ability of insulin to induce the release of nitric oxide and to enhance the expression of constitutive nitric oxide synthase.

	Specific dietary patterns may reduce inflammation

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
The raised flux of nutrients in the post-prandial state is associated with an increase in circulating levels of pro-inflammatory cytokines, recruitment of netrophils, and oxidative stress. As stated before, the generation of ROS may be a common ground for all these findings and may help understanding current dietetic recommendations emphasizing increased consumption of fruits, vegetables, and fibre, which contain a myriad of natural antioxidants that help fighting the oxidant wave of meals. Moreover, reducing trans- and saturated fatty acids intake and increasing the consumption of omega-3 fatty acids are also considered important strategies to reduce coronary heart disease (CHD) risk.³ It is interesting to note that these two strategies are also associated with a reduced inflammatory status. For instance, levels of C-reactive protein and markers of endothelial dysfunction are 73% higher in the highest quintile of trans-fatty acids intake in the Nurses' Health Study, compared with the lowest quintile,³⁰ and low-cholesterol/low-saturated fat diets are associated with mitigation of low-grade systemic inflammation which correlated with reduction of plasma C-reactive protein levels.³¹ Moreover, another cross-sectional study from the Nurses' Health Study I cohort demonstrated lower concentrations of many markers of inflammation and endothelial activation, including C-reactive protein, IL-6, and E-selectin, among those in the highest quintile of omega-3 fatty acids, when compared with the lowest quintile.³² There is a concern that a high intake of omega-6 fatty acids may reduce the known beneficial effects of omega-3 fatty acids on CHD risk; however, recent epidemiological evidence indicates that this fear may be unjustified, as combination of both types of fatty acids is associated with the lowest level of inflammation.³³

As oxidative processes are supposed to play a key role in the development of atherosclerosis, antioxidant–vitamin supplementation has been proposed for the treatment and prevention of chronic diseases, including coronary disease. The encouraging results of short-term trials in participants with coronary atherosclerosis³⁴ were not confirmed in large-size intervention trials. More recently, Miller et al.³⁵ reported the results of a carefully conducted meta-analysis of clinical trials of vitamin E supplementation concluding that high doses of this agent increase the risk for death. Their meta-analysis involved data from 19 randomized trials, which recorded 12 504 deaths. Overall, being randomly assigned to receive vitamin E had no effect, either positive or negative. However, the data suggested a decreased risk for death associated with vitamin E in trials that used lower doses (<400 IU) and showed a statistically significant trend towards increased risk at doses of 400 IU and above. Thus, it may be wrong to focus on a single element of the diet; guidelines from some professional or governmental panels recommend attempting to obtain vitamins and minerals from food sources rather than from supplements.³⁶

	Diet and cardiovascular health

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Recent epidemiological data support an important role of diet in reducing overall mortality. In particular, Knoops et al.³⁷ (Colleagues from the Netherlands, France, Spain, and Italy) have shown that in European men and women aged 70–90, adherence to a Mediterranean-style diet, which represents a solid example of a healthy dietary pattern, moderate alcohol consumption, non-smoking status, and physical activity, was associated with a lower rate of all-cause mortality. Taken together, the combination was associated with a mortality rate of about one-third that of those with none or only one of these protective factors. In a large prospective survey involving about 22 000 adults from Greece (the Greek cohort of the EPIC study), it has been shown an inverse correlation between a greater adherence to a Mediterranean-style diet and death.³⁸ In particular, approximately a 2/9 increment in the Mediterranean diet score was associated with a 25% reduction in total mortality and a 33% reduction in CHD mortality.

The two main intervention trials using the whole diet approach so far produced are also in line with this epidemiological evidence. In the Lyon Diet Heart Study,³⁹ 605 patients who had had a myocardial infarction were randomly assigned to a ‘Mediterranean-style’ diet or a control diet resembling the American Heart Association Step I diet. The Mediterranean diet model supplied 30% of energy from fats and <10% of energy from saturated fatty acids, whereas the intake of 18:3(n-3) (-linolenic acid) provided >0.6% of energy. After a mean follow-up of 27 months, the risk of new acute myocardial infarction and episodes of unstable angina was reduced by 70% by the Mediterranean diet. Moreover, total mortality was also reduced by 70%. Singh et al.⁴⁰ tested an ‘Indo-Mediterranean diet’ in 1000 patients in India with existing coronary disease or at high risk for coronary disease. When compared with the control diet, the intervention diet—characterized by increased intake of mustard or soyabean oil, nuts, vegetables, fruits, and whole grains—reduced the rate of fatal myocardial infarction by one-third and the rate of sudden death from cardiac causes by two-thirds.

Esposito et al.⁴¹ explored possible mechanisms underlying a whole dietary approach in patients at increased cardiac risk. The authors randomized 180 patients (99 men, 81 women) with the metabolic syndrome to a Mediterranean-style diet (instructions about increasing daily consumption of whole grains, vegetables, fruits, nuts, and olive oil) vs. a cardiac-prudent diet with fat intake <30%. Physical activity increased equally in both groups. After 2 years, patients on the Mediterranean diet showed greater weight loss, had lower C-reactive protein and pro-inflammatory cytokine levels, had less insulin resistance, had lower total cholesterol and triglyceride and higher HDL-cholesterol levels, and had a decreased prevalence of the metabolic syndrome, which was reduced approximately by one-half. These results suggest possible mechanisms for the beneficial effects of a Mediterranean-style diet.

The clustering atherogenic and diabetogenic abnormalities of the metabolic syndrome are highly prevalent in our affluent, sedentary populations.²⁷ The shift towards energy-dense, refined diet, which has been adopted by an increasing proportion of people, may have led to the development of a positive energy balance, weight gain, and obesity. Adipose tissue excess, particularly in the visceral compartment, is widely acknowledged as an endocrine organ secreting an increasing number of mediators, including pro-inflammatory cytokines.⁴² As visceral obesity is a key promoter of low-grade systemic inflammation^43–45 and is characterized by the most severe metabolic abnormalities,^46,47 it is possible that persons with abdominal adiposity are particularly prone to the pro-inflammatory effects of unhealthy diets. Although the evidence is still lacking, the Quebec Family Study has shown that a decrease in the consumption of fat-foods or an increase in consumption of whole fruits predicted a lower increase in body weight and adiposity indicators over a 6-year follow-up.⁴⁸ However, no specific dietary recommendations have been advocated by health agencies for the treatment of insulin resistance or the metabolic syndrome. Given that the metabolic syndrome is an identifiable and potentially modifiable risk state for both type 2 diabetes and cardiovascular disease, adopting a dietary pattern as that used in the study of Esposito et al.⁴¹ may reduce the potential risk of these diseases.

	Slow foods vs. fast foods

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 
Increased consumption of high-density and low-quality foods, such as those rich in refined starches, sugar, and unhealthy lipids (saturated and trans-fatty acids) and poor in natural antioxidants and fibre, may cause an activation of the innate immune system, most likely by an excessive production of pro-inflammatory cytokines associated with a reduced production of anti-inflammatory cytokines (Figure 1). This imbalance may favour the generation of a pro-inflammatory milieu, which in turn may produce insulin resistance in the peripheral tissues and endothelial dysfunction at the vascular level, and ultimately predispose susceptible people to an increased incidence of the metabolic syndrome and diabetes. The change in dietary patterns that occurred in recent years has introduced the consumption of a larger amount of foods that seem faster in preparation and in producing health damage. The recent findings from the prospective US CARDIA (Coronary Artery Risk Development in Young Adults) study show that frequent fast-food consumption is associated with weight gain and risk of insulin resistance over 15 years.⁴⁹ In practical terms, fully understanding the link between diet and inflammation holds the premise to elucidate the mechanisms by which dietary patterns improve cardiovascular health.

View larger version (14K): [in this window] [in a new window]   Figure 1 Dietary patterns high in refined starches, sugar, and lipids and poor in natural antioxidants and fibre may produce an inflammatory milieu characterized by raised ROS generation and unbalance between inflammatory and anti-inflammatory cytokines. Visceral obesity may also be favoured by ‘Western’ dietary patterns and contributes to inflammation. The risk of metabolic syndrome, type 2 diabetes, and atherosclerosis is ultimately increased by the separate or combined effects of inflammation, insulin resistance, and visceral obesity.

 
Inflammatory mechanisms appear to be important for mediating both metabolic insulin resistance and impaired insulin action in vascular endothelium that contribute to the relationship between metabolic and cardiovascular disorders. This has implications for novel therapeutic strategies because drugs that reduce inflammation would be predicted to improve both metabolic and endothelial functions. Indeed, recent clinical studies have demonstrated additive beneficial endothelial and metabolic effects of combining statins with angiotensin II type 1 receptor blockers in patients with type 2 diabetes.¹⁰ Moreover, reduction of post-prandial hyperglycaemia in type 2 diabetic patients has been shown to reduce the inflammatory milieu in association with regression of carotid atherosclerosis.⁷ However, these promising results cannot let us forget that appropriate dietary patterns, as those associated with the eating model of Mediterranean-type diets, represent rediscovered therapeutic strategies to reduce inflammation and the associated metabolic and cardiovascular risks. Fast-food habits seem to warm up inflammation, whereas slow-food habits cool it down.

Conflict of interest: none declared.

	References

Top Abstract Post-prandial state Macronutrients generates... From dietary inflammation to... Specific dietary patterns may... Diet and cardiovascular health Slow foods vs. fast... References

 

1. Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation 2002;105:2696–2698.[Free Full Text]
2. American Diabetes Association. The prevention or delay of type 2 diabetes (Position Statement). Diab Care 2004;27(Suppl. 1):S47–S54.
3. Hu FB, Willett WC. Optimal diets for prevention of coronary heart disease. JAMA 2002;288:2569–2578.[Abstract/Free Full Text]
4. Rimm EB, Stampfer MJ. Diet, lifestyle, and longevity—the next steps? JAMA 2004;292:1490–1492.[Free Full Text]
5. The World Health Report 2004. Global Strategy on Diet, Physical Activity, and Health. Geneva: World Health Organization; 2004;.
6. Ebenbichler CF, Kirchmair R, Egger JR, Patsch JR. Postprandial state and atherosclerosis. Curr Opin Lipidol 1995;6:286–290.[ISI][Medline]
7. Esposito K, Giugliano D, Nappo F, Marfella R for the Campanian Postprandial Hyperglycaemia Study Group. Regression of carotid atherosclerosis by control of post-prandial hyperglycaemia in type 2 diabetes mellitus. Circulation 2004;110:214–219.[CrossRef][ISI][Medline]
8. Nappo F, Esposito K, Cioffi M, Giugliano G, Molinari AM, Paolisso G, Marfella R, Giugliano D. Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol 2002;39:1145–1450.[Abstract/Free Full Text]
9. Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E. Evidence for an independent and cumulative effect of postprandial hypertriglyceridaemia and hyperglycaemia on endothelial dysfunction and oxidative stress generation. Circulation 2002;106: 1211–1218.[CrossRef][ISI][Medline]
10. Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro R, Esposito K, Giugliano D. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 2005;111: 2518–2524.[Abstract/Free Full Text]
11. Fard A, Tuck CH, Donis JA, Sciacca R, Di Tullio MR, Wu HD, Bryant TA, Chen NT, Torres-Tamayo M, Ramasamy R, Berglund R, Ginsberg HN, Homma S, Cannon PJ. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000;20:2039–2044.[Abstract/Free Full Text]
12. Lundman P, Eriksson MJ, Stuhlinger M, Cooke JP, Hamsten A, Tornvall P. Mild-to-moderate hypertriglyceridaemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol 2001;38:111–116.[Abstract/Free Full Text]
13. Boger RH. Association of asymmetric dimethylarginine and endothelial dysfunction. Clin Chem Lab Med 2003;41:1467–1472.[CrossRef][ISI][Medline]
14. Esposito K, Nappo F, Giugliano F, Giugliano G, Martella R, Giugliano D. Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects. Am J Clin Nutr 2003;77: 139–143.[Abstract/Free Full Text]
15. Bowen PE, Borthakur G. Postprandial lipid oxidation and cardiovascular risk. Curr Atheroscler Rep 2004;6:477–484.[Medline]
16. Ceriello A, Motz E. Is oxidative stress the pathogenetic mechanism underlying insulin resistance, diabetes and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004;24:816–823.[Abstract/Free Full Text]
17. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome. A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448–1454.[Free Full Text]
18. Esposito K, Nappo F, Marfella R, Gigliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycaemia in humans: role of oxidative stress. Circulation 2002;106:2067–2072.[CrossRef][ISI][Medline]
19. Ceriello A, Quagliaro L, Catone B, Pascon R, Piazzola M, Bais B, Marra G, Tonutti L, Toboga C, Motz E. The role of hyperglycaemia in nitrotyrosine postprandial generation. Diab Care 2002;25:1439–1443.[Abstract/Free Full Text]
20. Esposito K, Nappo F, Giugliano F, Di Palo C, Ciotola M, Barbieri M, Paolisso G, Giugliano D. Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus. Am J Clin Nutr 2003;78:1135–1140.[Abstract/Free Full Text]
21. Tataranni PA, Ortega E. A burning question. Does an adipokine-induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 2005; 54:917–927.[Abstract/Free Full Text]
22. Pankow JS, Duncam BB, Schmidt MI, Ballantyne CM, Couper DJ, Hoogeveen RC, Golden SH. Atherosclerotic Risk in Community Study. Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerotic risk in community study. Diab Care 2004;27:77–82.[Abstract/Free Full Text]
23. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004;291:1978–1986.[Abstract/Free Full Text]
24. Kim F, Tysseling KA, Julie R, Pham M, Haji L, Gallis BM, Baas AS, Paramshoty P, Giachelli CM, Corson MA, Raines EW. Free fatty acid impairment of nitric oxide production in endothelial cells is mediated by IKKß. Arterioscler Thromb Vasc Biol 2005;25:989–994.[Abstract/Free Full Text]
25. Gao Z, Hwang D, Bataille F, Lfevre M, York D, Quon MJ, Ye J. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 2002;277: 48115–48121.[Abstract/Free Full Text]
26. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK-b and NF-kappaB. Nat Med 2005;11:183–190.[CrossRef][ISI][Medline]
27. Esposito K, Giugliano D. The metabolic syndrome and inflammation: association or causation? Nutr Metab Cardiovasc Dis 2004;14:228–232.[CrossRef][ISI][Medline]
28. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–946.[CrossRef][ISI][Medline]
29. Dandona P, Aljiada A, Mohanty P. The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 2002;45:924–930.[CrossRef][ISI][Medline]
30. Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr 2005;135:562–566.[Abstract/Free Full Text]
31. Pirro M, Schillaci G, Savarese G, Gemelli F, Mannarino MR, Siepi D, Bagaglia F, Mannarino E. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil 2004;11:497–502.[CrossRef][ISI][Medline]
32. Lopez-Garcia E, Schulze MB, Manson JE, Albert CM, Rifai N, Willett WC, Wu FB. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 2004;134:1806–1811.[Abstract/Free Full Text]
33. Pischon T, Hankinson SE, Hotamisligil GS, Meigs JB, Rifai N, Willett WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation 2003;108:155–160.[CrossRef][ISI][Medline]
34. Rimm ER, Stampfer MJ. The role of antioxidants in preventive cardiology. Curr Opin Cardiol 1997;12:188–194.[ISI][Medline]
35. Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:37–46.[Abstract/Free Full Text]
36. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL for the Nutrition Committee of the American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004;110:637–641.[CrossRef][ISI][Medline]
37. Knoops KTB, de Groot LC, Kromhout D, Perrin AE, Moreiras-Varela O, Menotti A, van Staveren WA. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women. The HALE project. JAMA 2004;292:1433–1439.[Abstract/Free Full Text]
38. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003;348:2599–2608.[Abstract/Free Full Text]
39. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 1999;99:779–785.[ISI][Medline]
40. Singh RB, Dubnov G, Niaz MA, Ghosh S, Singh R, Rastogi SS, Manor O, Pella D, Berry EM. Effect of Indo-Mediterranean diet on progression of coronary disease in high risk patients: a randomized single blind trial. Lancet 2002;360:1455–1461.[CrossRef][ISI][Medline]
41. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D'Armiento M, D'Andrea F, Giugliano D. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004;292:1440–1446.[Abstract/Free Full Text]
42. Lau DCW, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: molecular links between obesity and atherosclerosis. Am J Physiol Heart Circ Physiol 2005;288:H2031–H2041.[Abstract/Free Full Text]
43. Gasteyger C, Tremblay A. Metabolic impact of body fat distribution. J Endocrinol Invest 2002;25:876–883.[ISI][Medline]
44. Diamant M, Lamb HJ, van de Ree MA, Endert EL, Groeneveld Y, Bots ML, Kostense PJ, Radder JK. The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes. J Clin Endocrinol Metab 2005;90:1495–1501.[Abstract/Free Full Text]
45. Piche ME, Lemieux S, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J. Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women. Am J Cardiol 2005;96:92–97.[CrossRef][ISI][Medline]
46. Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433–438.[CrossRef][ISI][Medline]
47. Després JP, Lemieux I, Prud'homme D. Treatment of obesity: need to focus on high risk abdominally obese patients. BMJ 2001;322:716–720.[Free Full Text]
48. Drapeau V, Despres JP, Bouchard C, Allard L, Fournier G, Leblanc C, Tremblay A. Modifications in food-group consumption are related to long-term body-weight changes. Am J Clin Nutr 2004;80:29–37.[Abstract/Free Full Text]
49. Pereira MA, Kartashow AI, Ebbeling CB, Van Horn L, Slattery ML, Jacobs DR Jr, Ludwig DS. Fast-food, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis. Lancet 2005;365:36–42.[CrossRef][ISI][Medline]

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