Clinical implications of oxidative stress and potential role of natural antioxidants in diabetic vascular complications

Nutrition, Metabolism and Cardiovascular Diseases

Volumn 26, Issue 4, 2016, Pages 285-292

  Ceriello, A ^a,b   Testa, R ^c   Genovese, S ^d  

^a INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c INRCA   (Italy)

^d IRCCS MULTIMEDICA   (Italy)

Author keywords

Antioxidants; Diabetes; Mediterranean diet; Oxidative stress; Reactive oxygen species; Vascular complications

Indexed keywords

ADVANCED GLYCATION END PRODUCT RECEPTOR; ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; CAROTENOID; CATECHIN; EPICATECHIN; FLAVONOID; FREE RADICAL; HEMOGLOBIN A1C; ISOTHIOCYANIC ACID DERIVATIVE; NICOTINAMIDE; PHOSPHATIDYLCHOLINE; POLYPHENOL DERIVATIVE; PROTEIN KINASE C; PYRIDOXINE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; SODIUM SELENITE; TRANSCRIPTION FACTOR RELA; ZINC SULFATE; ANTIDIABETIC AGENT; BIOLOGICAL MARKER;

ANTIOXIDANT ACTIVITY; BLOOD GLUCOSE MONITORING; DIABETIC ANGIOPATHY; DIABETIC RETINOPATHY; ENDOTHELIAL DYSFUNCTION; FOOD INTAKE; GENE EXPRESSION REGULATION; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INFLAMMATION; INSULIN DEPENDENT DIABETES MELLITUS; MEDITERRANEAN DIET; METABOLITE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATION; OXIDATIVE STRESS; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; VITAMIN SUPPLEMENTATION; BLOOD; CARDIOVASCULAR DISEASES; DIABETIC ANGIOPATHIES; DRUG POTENTIATION; METABOLISM; PATHOPHYSIOLOGY; VASCULAR ENDOTHELIUM;

ANTIOXIDANTS; BIOMARKERS; CARDIOVASCULAR DISEASES; DIABETIC ANGIOPATHIES; DIET, MEDITERRANEAN; DRUG SYNERGISM; ENDOTHELIUM, VASCULAR; HUMANS; HYPOGLYCEMIC AGENTS; OXIDATIVE STRESS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REACTIVE OXYGEN SPECIES;

EID: 84962276696     PISSN: 09394753     EISSN: 15903729     Source Type: Journal    
DOI: 10.1016/j.numecd.2016.01.006     Document Type: Review

References (117)

1. Singh D.K., Winocour P., Farrington K. Oxidative stress in early diabetic nephropathy: fueling the fire. Nat Rev Endocrinol 2011, 7:176-184.
2. Dröse S., Brandt U. Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv Exp Med Biol 2012, 748:145-169.
3. Hordijk P.L. Regulation of NADPH oxidases: the role of rac proteins. Circ Res 2006, 98:453-462.
4. Zhang D.X., Gutterman D.D. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 2007, 292:H2023-H2031.
5. Bedrad K., Krause K.H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007, 87:245-313.
6. Pacher P., Beckman J.S., Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev 2007, 87:315-424.
7. Zangar R.C., Davydov D.R., Verma S. Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 2004, 199:316-331.
8. Altenhöfer S., Kleikers P.W., Radermacher K.A., Scheurer P., Rob Hermans J.J., Schiffers P., et al. The NOX toolbox: validating the role of NADPH oxidases in physiology and disease. Cell Mol Life Sci 2012, 69:2327-2343.
9. Takac I., Schröder K., Zhang L., Lardy B., Anilkumar N., Lambeth J.D., et al. The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox 4. J Biol Chem 2011, 286:13304-13313.
10. Rodiño-Janeiro B.K., Paradela-Dobarro B., Castiñeiras-Landeira M.I., Raposeiras-Roubín S., González-Juanatey J.R., Alvarez E. Current status of NADPH oxidase research in cardiovascular pharmacology. Vasc Health Risk Manag 2013, 9:401-428.
11. Ristow M., Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 2010, 45:410-418.
12. Koskenkorva-Frank T.S., Weiss G., Koppenol W.H., Burckhardt S. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress. Free Radic Biol Med 2013, 65:1174-1194.
13. Pitocco D., Tesauro M., Alessandro R., Ghirlanda G., Cardillo C. Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci 2013, 14:21525-21550.
14. Lassègue B., San Martín A., Griendling K.K. Biochemistry, physiology and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 2012, 110:1364-1390.
15. Giugliano D., Ceriello A., Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996, 19:257-267.
16. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414:813-820.
17. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. Diabetes Care 2003, 26:1589-1596.
18. Ceriello A., Quagliaro L., D'Amico M., Di Filippo C., Marfella R., Nappo F., et al. Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 2002, 51:1076-1082.
19. Gupta M.M., Chari S. Lipid peroxidation and antioxidant status in patients with diabetic retinopathy. Indian J Physiol Pharmacol 2005, 49:187-192.
20. Drummond G.R., Selemidis S., Griendling K.K., Sobey C.G. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 2011, 10:453-471.
21. Konior A., Schramm A., Czesnikiewicz-Guzik M., Guzik T.J. NADPH oxidases in vascular pathology. Antioxid Redox Signal 2014, 20:2794-2814.
22. Teshima Y. Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase. Circ J 2014, 78:300-306.
23. Costacou T., Evans R.W., Schafer G.L., Orchard T.J. Oxidative stress and response in relation to coronary artery disease in type 1 diabetes. Diabetes Care 2013, 36:3503-3509.
24. Broedbaek K., Siersma V., Henriksen T., Weimann A., Petersen M., Andersen J.T., et al. Urinary markers of nucleic acid oxidation and long term mortality of newly diagnosed type 2 diabetic patients. Diabetes Care 2011, 34:2594-2596.
25. Broedbaek K., Siersma V., Henriksen T., Weimann A., Petersen M., Andersen J.T., et al. Association between urinary markers of nucleic acid oxidation and mortality in type 2 diabetes: a population-based cohort study. Diabetes Care 2013, 36:669-676.
26. Xu J., Zou M.H. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation 2009, 120:1266-1286.
27. Ceriello A. Hyperglycaemia and the vessel wall: the pathophysiological aspects on the atherosclerotic burden in patients with diabetes. Eur J Cardiovasc Prev Rehabil 2010, 17(Suppl. 1):S15-S19.
28. The Diabetes Control and Complications Trial Research Group The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993, 329:977-986.
29. UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352:837-853.
30. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005, 353:2643-2653.
31. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000, 342:381-389.
32. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003, 290:2159-2167.
33. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group, Nathan D.M., Zinman B., Cleary P.A., Backlund J.Y., Genuth S., et al. Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005). Arch Intern Med 2009, 169:1307-1316.
34. Gaede P., Lund-Andersen H., Parving H.H., Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008, 358:580-591.
35. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577-1589.
36. Lachin J.M., Orchard T.J., Nathan D.M. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care 2014, 37:39-43. DCCT/EDIC Research.
37. Ceriello A., Ihnat M.A., Thorpe J.E. Clinical review 2: the "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications?. J Clin Endocrinol Metab 2009, 94:410-415.
38. Genuth S., Sun W., Cleary P., Sell D.R., Dahms W., Malone J., et al. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes 2005, 54:3103-3111. for the DCCT Skin Collagen Ancillary Study Group.
39. Kowluru R.A. Mitochondria damage in the pathogenesis of diabetic retinopathy and in the metabolic memory associated with its continued progression. Curr Med Chem 2013, 20:3226-3233.
40. Ihnat M.A., Thorpe J.E., Kamat C.D., Szabó C., Green D.E., Warnke L.A., et al. Reactive oxygen species mediate a cellular 'memory' of high glucose stress signalling. Diabetologia 2007, 50:1523-1531.
41. Intine R.V., Sarras M.P. Metabolic memory and chronic diabetes complications: potential role for epigenetic mechanisms. Curr Diabetes Rep 2012, 12:551-559.
42. Ceriello A. The emerging challenge in diabetes: the "metabolic memory". Vasc Pharmacol 2012, 57:133-138.
43. Di Fulvio P., Pandolfi A., Formoso G., Di Silvestre S., Di Tomo P., Giardinelli A., et al. Features of endothelial dysfunction in umbilical cord vessels of women with gestational diabetes. Nutr Metab Cardiovasc Dis 2014, 24:1337-1345.
44. Esper R.J., Nordaby R.A., Vilariño J.O., Paragano A., Cacharrón J.L., Machado R.A. Endothelial dysfunction: a comprehensive appraisal. Cardiovasc Diabetol 2006, 5:4.
45. Ceriello A. Acute hyperglycaemia and oxidative stress generation. Diabet Med 1997, 14:S45-S49.
46. Ceriello A., Taboga C., Tonutti L., Quagliaro L., Piconi L., Bais B., et al. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 2002, 106:1211-1218.
47. Sørensen V.R., Mathiesen E.R., Clausen P., Flyvbjerg A., Feldt-Rasmussen B. Impaired vascular function during short-term poor glycaemic control in type 1 diabetic patients. Diabet Med 2005, 22:871-876.
48. Huvers F.C., De Leeuw P.W., Houben A.J., De Haan C.H., Hamulyak K., Schouten H., et al. Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions. Diabetes 1999, 48:1300-1307.
49. Dogra G., Rich L., Stanton K., Watts G.F. Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria. Diabetologia 2001, 44:593-601.
50. Ceriello A., Kumar S., Piconi L., Esposito K., Giugliano D. Simultaneous control of hyperglycemia and oxidative stress normalizes endothelial function in type 1 diabetes. Diabetes Care 2007, 30:649-654.
51. Mullan B.A., Ennis C.N., Fee H.J., Young I.S., McCance D.R. Pretreatment with intravenous ascorbic acid preserves endothelial function during acute hyperglycaemia. Clin Exp Pharmacol Physiol 2005, 32:340-345.
52. Ceriello A., Esposito K., Ihnat M., Thorpe J., Giugliano D. Long-term glycemic control influences the long-lasting effect of hyperglycemia on endothelial function in type 1 diabetes. J Clin Endocrinol Metab 2009, 94:2751-2756.
53. Ceriello A., Esposito K., Ihnat M., Thorpe J., Giugliano D. Effect of acute hyperglycaemia, long-term glycaemic control and insulin on endothelial dysfunction and inflammation in type 1 diabetic patients with different characteristics. Diabet Med 2010, 27:911-917.
54. Monnier L., Colette C., Owens D.R. Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it?. J Diabetes Sci Technol 2008, 2:1094-1100.
55. Ceriello A. Postprandial hyperglycemia and diabetes complications: is it time to treat?. Diabetes 2005, 54:1-7.
56. Ceriello A. The glucose triad and its role in comprehensive glycaemic control: current status, future management. Int J Clin Pract 2010, 64:1705-1711.
57. Rodbard D. Glycemic variability: measurement and utility in clinical medicine and research-one viewpoint. Diabetes Technol Ther 2011, 13:1077-1080.
58. Quagliaro L., Piconi L., Assaloni R., Martinelli L., Motz E., Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 2003, 52:2795-2804.
59. Quagliaro L., Piconi L., Assaloni R., Da Ros R., Maier A., Zuodar G., et al. Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production. Atherosclerosis 2005, 183:259-267.
60. Ceriello A., Esposito K., Piconi L., Ihnat M.A., Thorpe J.E., Testa R., et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008, 57:1349-1354.
61. Monnier L., Mas E., Ginet C., Michel F., Villon L., Cristol J.P., et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006, 295:1681-1687.
62. El-Osta A., Brasacchio D., Yao D., Pocai A., Jones P.L., Roeder R.G., et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 2008, 205:2409-2417.
63. Ceriello A., Kilpatrick E.S. Glycemic variability: both sides of the story. Diabetes Care 2013, 36:S272-S275.
64. Kilpatrick E.S., Rigby A.S., Atkin S.L. For debate. Glucose variability and diabetes complication risk: we need to know the answer. Diabet Med 2010, 27:868-871.
65. Kilpatrick E.S., Rigby A.S., Atkin S.L. A1C variability and the risk of microvascular complications in type 1 diabetes. Diabetes Care 2008, 31:2198-2202.
66. Marcovecchio M.L., Dalton R.N., Chiarelli F., Dunger D.B. A1C variability as an independent risk factor for microalbuminuria in young people with type 1 diabetes. Diabetes Care 2011, 34:1011-1013.
67. Wadén J., Forsblom C., Thorn L.M., Gordin D., Saraheimo M., Groop P.H. A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes. Diabetes 2009, 58:2649-2655. Finnish Diabetic Nephropathy Study Group.
68. Sugawara A., Kawai K., Motohashi S., Saito K., Kodama S., Yachi Y., et al. HbA(1c) variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2. Diabetologia 2012, 55:2128-2131.
69. Penno G., Solini A., Bonora E., Fondelli C., Orsi E., Zerbini G., et al. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study. Diabetes Care 2013, 36:2301-2310. Renal Insufficiency And Cardiovascular Events Study Group.
70. Patel A., MacMahon S., Chalmers J., Neal B., Billot L., Woodward M., et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008, 358:2560-2572. ADVANCE Collaborative Group.
71. Muggeo M., Zoppini G., Bonora E., Brun E., Bonadonna R.C., Moghetti P., et al. Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients. Diabetes Care 2000, 23:45-50.
72. Lin C.C., Li C.I., Yang S.Y., Liu C.S., Chen C.C., Fuh M.M., et al. Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. Am J Med 2012, 125. 416.e9-18.
73. Hirakawa Y., Arima H., Zoungas S., Ninomiya T., Cooper M., Hamet P., et al. Impact of visit-to visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care 2014, 37:2359-2365.
74. Hanefeld M., Duetting E., Bramlage P. Cardiac implications of hypoglycaemia in patients with diabetes - a systematic review. Cardiovasc Diabetol 2013, 12:135.
75. Johnston S.S., Conner C., Aagren M., Smith D.M., Bouchard J., Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care 2011, 34:1164-1170.
76. Bedenis R., Price A.H., Robertson C.M., Morling J.R., Frier B.M., Strachan M.W., et al. Association between severe hypoglycemia, adverse macrovascular events, and inflammation in the Edinburgh type 2 diabetes study. Diabetes Care 2014, 37:3301-3308.
77. Desouza C.V., Bolli G.B., Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 2010, 33:1389-1394.
78. Chouchani E.T., Pell V.R., Gaude E., Aksentijević D., Sundier S.Y., Robb E.L., et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 2014, 515:431-435.
79. Ceriello A., Novials A., Ortega E., La Sala L., Pujadas G., Testa R., et al. Evidence that hyperglycemia after recovery from hypoglycemia worsens endothelial function and increases oxidative stress and inflammation in healthy control subjects and subjects with type 1 diabetes. Diabetes 2012, 61:2993-2997.
80. Ceriello A., Novials A., Ortega E., Pujadas G., La Sala L., Testa R., et al. Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls. Nutr Metab Cardiovasc Dis 2014, 24:116-123.
81. Kowluru R.A., Zhong Q., Santos J.M., Thandampallayam M., Putt D., Gierhart D.L. Beneficial effects of the nutritional supplements on the development of diabetic retinopathy. Nutr Metab 2014, 11:8.
82. Kowluru R.A., Tang J., Kern T.S. Abnormalities of retinal metabolism in diabetes and experimental galactosemia VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 2001, 50:1938-1942.
83. Kowluru R.A., Zhong Q. Beyond AREDS: is there a place for anti-oxidant therapy in the prevention/treatment of eye disease?. Investig Ophthalmol Vis Sci 2011, 52:8665-8671.
84. Kowluru R.A., Menon B., Gierhart D. Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rat. Investig Ophthalmol Vis Sci 2008, 49:1645-1651.
85. Giorgio M. Oxidative stress and the unfulfilled promises of antioxidant agents. Ecancermedicalscience 2015 Jul 23, 9:556. eCollection 2015. 10.3332/ecancer.2015.556.
86. Sacco M., Pellegrini F., Roncaglioni M.C., Avanzini F., Tognoni G., Nicolucci A. Primary prevention of cardiovascular events with low-dose aspirin and vitamin E in type 2 diabetic patients: results of the Primary Prevention Project (PPP) trial. Diabetes Care 2003, 26:3264-3272. PPP Collaborative Group.
87. The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000, 342:154-160.
88. Gerstein H.C., Bosch J., Pogue J., Taylor D.W., Zinman B., Yusuf S. Rationale and design of a large study to evaluate the renal and cardiovascular effects of an ACE inhibitor and vitamin E in high-risk patients with diabetes: the MICRO-HOPE study. Diabetes Care 1996, 19:1225-1228. for the HOPE Study Investigators.
89. Lonn E., Bosch J., Yusuf S., Sheridan P., Pogue J., Arnold J.M., et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005, 293:1338-1347. HOPE and HOPE-TOO Trial Investigators.
90. Blum S., Vardi M., Brown J.B., Russell A., Milman U., Shapira C., et al. Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics 2010, 11:675-684.
91. Milman U., Blum S., Shapira C., Aronson D., Miller-Lotan R., Anbinder Y., et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective, double-blinded clinical trial. Arterioscler Thromb Vasc Biol 2008, 28:341-347.
92. Vardi M., Blum S., Levy A.P. Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus - natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature. Eur J Intern Med 2012, 23:628-632.
93. Belch J., MacCuish A., Campbell I., Cobbe S., Taylor R., Prescott R., et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008, 337:a1840. Prevention of Progression of Arterial Disease and Diabetes Study Group, Diabetes Registry GroupDiabetes Registry Group, Royal College of Physicians EdinburghRoyal College of Physicians Edinburgh.
94. Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A., et al. Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst 1996, 88:1550-1559.
95. Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A., et al. Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996, 334:1150-1155.
96. Lu L.Y., Ou N., Lu Q.B. Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells. Sci Rep 2013, 3:3169.
97. Estruch R., Ros E., Salas-Salvadó J., Covas M.I., Corella D., Arós F., et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013, 368:1279-1290. PREDIMED Study Investigators.
98. Psaltopoulou T., Panagiotakos D.B., Pitsavos C., Chrysochoou C., Detopoulou P., Skoumas J., et al. Dietary antioxidant capacity is inversely associated with diabetes biomarkers: the ATTICA study. Nutr Metab Cardiovasc Dis 2011, 21:561-567.
99. Mekary R.A., Wu K., Giovannucci E., Sampson L., Fuchs C., Spiegelman D., et al. Total antioxidant capacity intake and colorectal cancer risk in the health professionals follow-up study. Cancer Causes Control 2010, 21:1315-1321.
100. Serafini M., Jakszyn P., Luján-Barroso L., Agudo A., Bas Bueno-de-Mesquita H., van Duijnhoven F.J., et al. Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study. Int J Cancer 2012, 131:544-554.
101. Zamora-Ros R., Serafini M., Estruch R., Lamuela-Raventós R.M., Martínez-González M.A., Salas-Salvadó J., et al. Mediterranean diet and non enzymatic antioxidant capacity in the PREDIMED study: evidence for a mechanism of antioxidant tuning. Nutr Metab Cardiovasc Dis 2013, 23:1167-1174. PREDIMED Study Investigators.
102. Castañer O., Corella D., Covas M.I., Sorlí J.V., Subirana I., Flores-Mateo G., et al. In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: a randomized controlled trial. Am J Clin Nutr 2013, 98:845-853. PREDIMED Study Investigators.
103. Martínez-González M.A., Salas-Salvadó J., Estruch R., Corella D., Fitó M., Ros E. Benefits of the Mediterranean diet: insights from the PREDIMED study. Prog Cardiovasc Dis 2015, 58:50-60. PREDIMED Investigators.
104. Casas R., Sacanella E., Urpí-Sardà M., Chiva-Blanch G., Ros E., Martínez-González M.A., et al. The effects of the Mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial. PLoS One 2014, 9:e100084.
105. Díaz-López A., Babio N., Martínez-González M.A., Corella D., Amor A.J., Fitó M., et al. Mediterranean diet, retinopathy, nephropathy, and microvascular diabetes complications: a post hoc analysis of a randomized trial. Diabetes Care 2015 Sep 13, PREDIMED Study Investigators, pii: dc151117. [Epub ahead of print].
106. Bahadoran Z., Mirmiran P., Azizi F. Potential efficacy of broccoli sprouts as a unique supplement for management of type 2 diabetes and its complications. J Med Food 2013, 16:375-382.
107. Hegde S.V., Adhikari P.M.N., D'Souza V. Effect of daily supplementation of fruits on oxidative stress indices and glycaemic status in type 2 diabetes mellitus. Complement Ther Clin Pract 2013, 19:97-100.
108. Parsaeyan N., Mozaffari Khosravi H., Absalan A., Mozayan M.R. Beneficial effects of cocoa on lipid peroxidation and inflammatory markers in type 2 diabetic patients and investigation of probable interactions of cocoa active ingredients with prostaglandin synthase-2 (PTGS-2/COX-2) using virtual analysis. J Diabetes Metab Disord 2014, 13:30.
109. Subhash K., Bose C., Agrawal B.K. Effect of short supplementation od tomatoes on antioxidant enzymes and lipid peroxidation in type 2 diabetes. Indian J Clin Biochem 2007, 22:95-98.
110. Di Tomo P., Canali R., Ciavardelli D., Di Silvestre S., De Marco A., Giardinelli A., et al. β-Carotene and lycopene affect endothelial response to TNF-α reducing nitro-oxidative stress and interaction with monocytes. Mol Nutr Food Res 2012, 56:217-227.
111. Müllner E., Brath H., Pleifer S., Schiermayr C., Baierl A., Wallner M., et al. Vegetables and PUFA-rich plant oil reduce DNA strand breaks in individuals with type 2 diabetes. Mol Nutr Food Res 2013, 57:328-338.
112. Erejuwa O.O. Effect of honey in diabetes mellitus: matters arising. J Diabetes Metab Disord 2014, 13:23.
113. Erejuwa O.O., Sulaiman S.A., Wahab M.S. Honey: a novel antioxidant. Molecules 2012, 17:4400-4423.
114. Ceriello A., Bortolotti N., Motz E., Lizzio S., Russo A., Selmo V., et al. Meal-generated oxidative stress in diabetes. The protective effect of red wine. Diabetes Care 1999, 22:2084-2085.
115. Robertson R.P. Red wine and diabetes health: getting skin in the game. Diabetes 2014, 63:31-38.
116. Bahadoran Z., Mirmiran P., Azizi F. Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. J Diabetes Metab Disord 2013, 12:43.
117. Ceriello A., Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004, 24:816-823.