Current Nutrition Reports

, Volume 6, Issue 3, pp 247–256 | Cite as

Inflammation: a New Player in the Link Between Mediterranean Diet and Diabetes Mellitus: a Review

  • Efi Koloverou
  • Demosthenes B. Panagiotakos
Cardiovascular Disease (JHY Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cardiovascular Disease


Purpose of Review

Mediterranean diet (MD) has been inversely linked with insulin resistance and diabetes, while inflammation is recognized as a common denominator in cardiometabolic disorders. Here, we review the synergistic effect between MD and inflammation, the anti-inflammatory properties of core MD components, and the possible biological mechanisms linking nutrients with inflammation.

Recent Findings

MD is abundant in anti-inflammatory foods, like whole grains, fruits and vegetables, wine, olive oil, nuts, and fish. This results in a high intake of various polyphenols, as well as high unsaturated/saturated and n3/n6 fatty acid ratios, leading through different mechanisms, such as oxidative stress reduction, alteration of NF-κB, PPAR-γ pathways, prebiotic function on gut microbiota, and others, to an attenuation of inflammation state.


MD is comprised by a plethora of foods, with anti-inflammatory potential, so its observed anti-diabetic effect could, at least partially, be ascribed to an attenuation of inflammation state.


Mediterranean diet Diabetes Inflammation Cardiometabolic disorders 


Compliance with Ethical Standards

Conflict of Interest

Efi Koloverou and Demosthenes B. Panagiotakos declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does contain studies with human subjects performed by any of the authors. For these studies, informed consent had been provided.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Keys A, et al. The diet and 15-year death rate in the seven countries study. Am J Epidemiol. 1986;124(6):903–15.CrossRefPubMedGoogle Scholar
  2. 2.
    Koloverou E, et al. The effect of Mediterranean diet on the development of type 2 diabetes mellitus: a meta-analysis of 10 prospective studies and 136,846 participants. Metabolism. 2014;63(7):903–11.CrossRefGoogle Scholar
  3. 3.
    Psaltopoulou T, et al. Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann Neurol. 2013;74(4):580–91.CrossRefPubMedGoogle Scholar
  4. 4.
    Schwingshackl L, Hoffmann G. Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies. Cancer Med. 2015;4(12):1933–47.CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Willett WC, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995;61(6 Suppl):1402S–6S.PubMedGoogle Scholar
  6. 6.
    UNESCO. Representative list of the intangible cultural heritage of humanity. 2010.
  7. 7.
    Bach-Faig A, et al. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 2011;14(12A):2274–84.CrossRefPubMedGoogle Scholar
  8. 8.
    Trichopoulou A, et al. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348(26):2599–608.CrossRefPubMedGoogle Scholar
  9. 9.
    Estruch R, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Salas-Salvado J, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011;34(1):14–9.CrossRefGoogle Scholar
  11. 11.
    Koloverou E, et al. Adherence to Mediterranean diet and 10-year incidence (2012–2014) of diabetes: correlations with inflammatory and oxidative stress biomarkers in the ATTICA cohort study Diabetes Metab Res Rev. 2016;32(1):73–81.Google Scholar
  12. 12.
    Panagiotakos DB, et al. Exploring the path of Mediterranean diet on 10-year incidence of cardiovascular disease: the ATTICA study (2002-2012). Nutr Metab Cardiovasc Dis. 2015;25(3):327–35.CrossRefPubMedGoogle Scholar
  13. 13.
    Garcia M, et al. The effect of the traditional Mediterranean-style diet on metabolic risk factors: a meta-analysis. Nutrients. 2016;8(3):168.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kastorini CM, et al. The effect of Mediterranean diet on metabolic syndrome and its components: a meta-analysis of 50 studies and 534,906 individuals. J Am Coll Cardiol. 2011;57(11):1299–313.CrossRefPubMedGoogle Scholar
  15. 15.
    Huo R, et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. Eur J Clin Nutr. 2015;69(11):1200–8.CrossRefGoogle Scholar
  16. 16.
    Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11(2):98–107.CrossRefPubMedGoogle Scholar
  17. 17.
    Montecucco F, et al. The role of inflammation in cardiovascular outcome. Curr Atheroscler Rep. 2017;19(3):11.CrossRefPubMedGoogle Scholar
  18. 18.
    Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116(7):1793–801.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Torres-Leal F, et al. Adipose tissue inflammation and insulin resistance. Insulin Resistance, ed. D.S. Arora. 2012: InTech.
  20. 20.
    Cawthorn WP, Sethi JK. TNF-alpha and adipocyte biology. FEBS Lett. 2008;582(1):117–31.CrossRefPubMedGoogle Scholar
  21. 21.
    Karpe F, Dickmann JR, Frayn KN. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes. 2011;60(10):2441–9.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang X, et al. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36(1):166–75.CrossRefPubMedGoogle Scholar
  23. 23.
    Guilherme A, et al. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9(5):367–77.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Queiroz JC, et al. Control of adipogenesis by fatty acids. Arq Bras Endocrinol Metabol. 2009;53(5):582–94.CrossRefPubMedGoogle Scholar
  25. 25.
    Harman-Boehm I, et al. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab. 2007;92(6):2240–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Muris DM, et al. Microvascular dysfunction is associated with a higher incidence of type 2 diabetes mellitus: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol. 2012;32(12):3082–94.CrossRefPubMedGoogle Scholar
  27. 27.
    Muniyappa R, Sowers JR. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord. 2014;14(1):5–12.CrossRefGoogle Scholar
  28. 28.
    Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III27–32.PubMedGoogle Scholar
  29. 29.
    Rubbo H, et al. Interactions of nitric oxide and peroxynitrite with low-density lipoprotein. Biol Chem. 2002;383(3–4):547–52.PubMedGoogle Scholar
  30. 30.
    Steinberg D, Witztum JL. Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation. 2002;105(17):2107–11.CrossRefPubMedGoogle Scholar
  31. 31.
    Hulsmans M, Holvoet P. The vicious circle between oxidative stress and inflammation in atherosclerosis. J Cell Mol Med. 2010;14(1–2):70–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Ridker PM, Luscher TF. Anti-inflammatory therapies for cardiovascular disease. Eur Heart J. 2014;35(27):1782–91.CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Kaptoge S, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014;35(9):578–89.CrossRefPubMedGoogle Scholar
  34. 34.
    Fung TT, et al. Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2005;82(1):163–73.PubMedGoogle Scholar
  35. 35.
    Ambring A, et al. Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects. Am J Clin Nutr. 2006;83(3):575–81.PubMedGoogle Scholar
  36. 36.
    Esposito K, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003;289(14):1799–804.CrossRefPubMedGoogle Scholar
  37. 37.
    Panagiotakos DB, et al. Association between the prevalence of obesity and adherence to the Mediterranean diet: the ATTICA study. Nutrition. 2006;22(5):449–56.CrossRefPubMedGoogle Scholar
  38. 38.
    Estruch R, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: A randomized trial. Ann Intern Med. 2006;145(1):1–11.CrossRefPubMedGoogle Scholar
  39. 39.
    Urpi-Sarda M, et al. The Mediterranean diet pattern and its main components are associated with lower plasma concentrations of tumor necrosis factor receptor 60 in patients at high risk for cardiovascular disease. J Nutr. 2012;142(6):1019–25.CrossRefPubMedGoogle Scholar
  40. 40.
    Schwingshackl L, Hoffmann G. Mediterranean dietary pattern, inflammation and endothelial function: a systematic review and meta-analysis of intervention trials. Nutr Metab Cardiovasc Dis. 2014;24(9):929–39.CrossRefPubMedGoogle Scholar
  41. 41.
    Marin C, et al. Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium. Am J Clin Nutr. 2011;93(2):267–74.CrossRefGoogle Scholar
  42. 42.
    Gomez-Delgado F, et al. Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial. Mol Nutr Food Res. 2014;58(7):1519–27.CrossRefGoogle Scholar
  43. 43.
    Katcher HI, et al. The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr. 2008;87(1):79–90.PubMedGoogle Scholar
  44. 44.
    Qi L, et al. Dietary glycemic index, glycemic load, cereal fiber, and plasma adiponectin concentration in diabetic men. Diabetes Care. 2005;28(5):1022–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Mantzoros CS, et al. Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women. Am J Clin Nutr. 2006;84(2):328–35.PubMedGoogle Scholar
  46. 46.
    Jensen MK, et al. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1. Am J Clin Nutr. 2006;83(2):275–83.PubMedGoogle Scholar
  47. 47.
    Widmer RJ, et al. The Mediterranean diet, its components, and cardiovascular disease. Am J Med. 2015;128(3):229–38.CrossRefPubMedGoogle Scholar
  48. 48.
    Hermsdorff HH, et al. Fruit and vegetable consumption and proinflammatory gene expression from peripheral blood mononuclear cells in young adults: a translational study. Nutr Metab (Lond). 2010;7:42.CrossRefGoogle Scholar
  49. 49.
    Bhupathiraju SN, Tucker KL. Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. Am J Clin Nutr. 2011;93(1):37–46.CrossRefGoogle Scholar
  50. 50.
    Calder PC, et al. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr. 2011;106(Suppl 3):S5–78.CrossRefPubMedGoogle Scholar
  51. 51.
    Schwingshackl L, Christoph M, Hoffmann G. Effects of olive oil on markers of inflammation and endothelial function—a systematic review and meta-analysis. Nutrients. 2015;7(9):7651–75.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Calabriso N, et al. Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression. J Nutr Biochem. 2015;28:19–29.CrossRefPubMedGoogle Scholar
  53. 53.
    Jiang R, et al. Nut and seed consumption and inflammatory markers in the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2006;163(3):222–31.CrossRefPubMedGoogle Scholar
  54. 54.
    Mukuddem-Petersen J, et al. Effects of a high walnut and high cashew nut diet on selected markers of the metabolic syndrome: a controlled feeding trial. Br J Nutr. 2007;97(6):1144–53.CrossRefPubMedGoogle Scholar
  55. 55.
    Sari I, et al. Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study. Nutrition. 2010;26(4):399–404.CrossRefPubMedGoogle Scholar
  56. 56.
    Banel DK, Hu FB. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review. Am J Clin Nutr. 2009;90(1):56–63.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Ros E. Nuts and novel biomarkers of cardiovascular disease. Am J Clin Nutr. 2009;89(5):1649S–56S.CrossRefPubMedGoogle Scholar
  58. 58.
    Chrysohoou C, et al. Effects of chronic alcohol consumption on lipid levels, inflammatory and haemostatic factors in the general population: the ‘ATTICA’ study. Eur J Cardiovasc Prev Rehabil. 2003;10(5):355–61.CrossRefPubMedGoogle Scholar
  59. 59.
    Beulens JW, et al. Alcohol consumption, mediating biomarkers, and risk of type 2 diabetes among middle-aged women. Diabetes Care. 2008;31(10):2050–5.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Blanco-Colio LM, et al. Red wine intake prevents nuclear factor-kappaB activation in peripheral blood mononuclear cells of healthy volunteers during postprandial lipemia. Circulation. 2000;102(9):1020–6.CrossRefPubMedGoogle Scholar
  61. 61.
    van Bussel BC, et al. Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn study. Eur J Nutr. 2017.
  62. 62.
    Liu K, et al. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr, 2014;99(6):1510–9Google Scholar
  63. 63.
    Turunen AW, et al. Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis. Environ Res. 2013;120:43–54.CrossRefPubMedGoogle Scholar
  64. 64.
    Cormier H, et al. Expression and sequence variants of inflammatory genes; effects on plasma inflammation biomarkers following a 6-week supplementation with fish oil. Int J Mol Sci. 2016;17(3):375.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Lin N, et al. What is the impact of n-3 PUFAs on inflammation markers in type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis. 2016;15:133.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Clarke SD. The multi-dimensional regulation of gene expression by fatty acids: polyunsaturated fats as nutrient sensors. Curr Opin Lipidol. 2004;15(1):13–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Staiger H, et al. Fatty acid-induced differential regulation of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in human skeletal muscle cells that have been differentiated in vitro. Diabetologia. 2005;48(10):2115–8.CrossRefPubMedGoogle Scholar
  68. 68.
    Kim JK. Fat uses a TOLL-road to connect inflammation and diabetes. Cell Metab. 2006;4(6):417–9.CrossRefPubMedGoogle Scholar
  69. 69.
    Fazzari M, et al. Olives and olive oil are sources of electrophilic fatty acid nitroalkenes. PLoS One. 2014;9(1):e84884.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Freeman BA, et al. Nitro-fatty acid formation and signaling. J Biol Chem. 2008;283(23):15515–9.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Imamura F, et al. Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: a systematic review and meta-analysis of randomised controlled feeding trials. PLoS Med. 2016;13(7):e1002087.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Schroder H. Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes. J Nutr Biochem. 2007;18(3):149–60.CrossRefPubMedGoogle Scholar
  73. 73.
    Calder PC. Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale. Biochimie. 2009;91(6):791–5.CrossRefGoogle Scholar
  74. 74.
    •• Scoditti E, et al. Vascular effects of the Mediterranean diet-Part II: role of omega-3 fatty acids and olive oil polyphenols. Vascul Pharmacol. 2014;63(3):127–34. This paper provides a comprehensive discussion of the effects of n3 fatty acids and olive oil polyphenols on inflammatory processes. CrossRefGoogle Scholar
  75. 75.
    Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. J Acad Nutr Diet. 2012;112(7):1029–41. 1041 e1–15CrossRefGoogle Scholar
  76. 76.
    Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep. 2006;8(6):453–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Godos J, et al. Dietary sources of polyphenols in the Mediterranean healthy eating, aging and lifestyle (MEAL) study cohort. Int J Food Sci Nutr. 2017:1–7.Google Scholar
  78. 78.
    Sun B, et al. Fractionation of red wine polyphenols by solid-phase extraction and liquid chromatography. J Chromatogr A. 2006;1128(1–2):27–38.CrossRefPubMedGoogle Scholar
  79. 79.
    Joseph SV, Edirisinghe I, Burton-Freeman BM. Fruit polyphenols: a review of anti-inflammatory effects in humans. Crit Rev Food Sci Nutr. 2015;56(3):419–44.CrossRefGoogle Scholar
  80. 80.
    Manach C, et al. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727–47.PubMedGoogle Scholar
  81. 81.
    Basli A, et al. Wine polyphenols: potential agents in neuroprotection. Oxidative Med Cell Longev. 2012;2012:805762.CrossRefGoogle Scholar
  82. 82.
    Covas MI, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006;145(5):333–41.CrossRefGoogle Scholar
  83. 83.
    Moreno-Luna R, et al. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens. 2012;25(12):1299–304.PubMedGoogle Scholar
  84. 84.
    Lucas L, Russell A, Keast R. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal. Curr Pharm Des. 2011;17(8):754–68.CrossRefPubMedGoogle Scholar
  85. 85.
    Forman HJ, Davies KJ, Ursini F. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med. 2013;66:24–35.CrossRefPubMedGoogle Scholar
  86. 86.
    • Crasc IL, et al. Natural antioxidant polyphenols on inflammation management: anti-glycation activity vs metalloproteinases inhibition. Crit Rev Food Sci Nutr, 2016: p. 0. This paper presents a novel anti-inflammatory mechanism of polyphenols through inhibition of AGEs at different levels of the glycation process. Google Scholar
  87. 87.
    • Cueva C, et al. An integrated view of the effects of wine polyphenols and their relevant metabolites on gut and host health. Molecules, 2017. 22(1). This paper discusses the prebiotic effect of wine polyphenols on gut microbiota, suggesting a novel link between polyphenol and inflammation. Google Scholar
  88. 88.
    de Vos WM, Nieuwdorp M. Genomics: a gut prediction. Nature. 2013;498(7452):48–9.CrossRefGoogle Scholar
  89. 89.
    Panagiotakos DB, Pitsavos C, Stefanadis C. Inclusion of dietary evaluation in cardiovascular disease risk prediction models increases accuracy and reduces bias of the estimations. Risk Anal. 2009;29(2):176–86.CrossRefGoogle Scholar
  90. 90.
    Maestre R, et al. Alterations in the intestinal assimilation of oxidized PUFAs are ameliorated by a polyphenol-rich grape seed extract in an in vitro model and Caco-2 cells. J Nutr. 2013;143(3):295–301.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.School of Health, Science and Education, Department of Nutrition and DieteticsHarokopio UniversityAthensGreece

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