Reviews in Endocrine and Metabolic Disorders

, Volume 17, Issue 1, pp 111–116 | Cite as

Atherogenicity of postprandial hyperglycemia and lipotoxicity

  • Antonio Ceriello
  • Stefano Genovese


Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose regulation. However, physicians continue to rely on fasting plasma glucose and glycated hemoglobin to guide management. There is a linear relationship between the risk of cardiovascular death and the 2-h oral glucose tolerance test, while a study confirms postprandial hyperglycemia as independent risk factor for cardiovascular disease in type 2 diabetes. At the same time, several studies show that postprandial hypertriglyceridemia may also be a cardiovascular risk factor. Interestingly, the simultaneous presence of postprandial hyperglycemia and postprandial hypertriglyceridemia has an additive effect in worsening endothelial function and inflammation. Evidence supports the hypothesis glucose postprandial hyperglycemia and hypertriglyceridemia may favor the appearance of the cardiovascular disease through the generation of an oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycemia is a common phenomenon even in patients who may be considered in “good metabolic control”. Therefore, physicians should consider monitoring and targeting postprandial plasma glucose, as well as glycated hemoglobin and fasting plasma glucose, in patients with type 2 diabetes.


Postprandial hyperglycemia Postprandial hyperlipidemia Oxidative stress Endothelial dysfunction 


Compliance with ethical standards

Conflicts of interest

The authors do not have conflicts of interest to declare.


  1. 1.
    Del Prato S Megatrials in type 2 diabetes. from excitement to frustration? Diabetologia. 2009;52:1219–26.CrossRefPubMedGoogle Scholar
  2. 2.
    Ceriello A, Hanefeld M, Leiter L, Monnier L, Moses A, Owens D, Tajima N, Tuomilehto J. Postprandial glucose regulation and diabetic complications. Arch Intern Med. 2004;16:2090–5.CrossRefGoogle Scholar
  3. 3.
    Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation. 1979;60:473–85.CrossRefPubMedGoogle Scholar
  4. 4.
    Bonora E, Muggeo M. Postprandial blood glucose as a risk factor for cardiovascular disease in type II diabetes: the epidemiological evidence. Diabetologia. 2001;44:2107–14.CrossRefPubMedGoogle Scholar
  5. 5.
    Meigs JB, Nathan DM, D’Agostino Sr RB, Wilson PW. Fasting and post-challenge glycemia and cardiovascular disease risk: the Framingham offspring study. Diabetes Care. 2002;25:1845–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Hanefeld M, Fischer S, Julius U, et al. Risk factors for myocardial infarction and death in newly detected NIDDM: the diabetes intervention study, 11-year follow-up. Diabetologia. 1996;39:1577–83.CrossRefPubMedGoogle Scholar
  7. 7.
    Cavalot F, Petrelli A, Traversa M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women. J Clin Endocrinol Metab. 2006;91:813–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Cavalot F, Pagliarino A, Valle M, Di Martino L, Bonomo K, Massucco P, Anfossi G, Trovati M. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes study. Diabetes Care. 2011;34:2237–43.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Carlson LA, Boettiger LE. Risk factors for ischemic disease in men and women. results of the 19-year follow-up of the Stockholm prospective study. acta med. Scand. 1985;218:207–11.Google Scholar
  10. 10.
    Susanna B, Giacomo R, Rong T, Johan B. Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men. Circulation. 1999;100:723–8.CrossRefGoogle Scholar
  11. 11.
    Koskinen P, Manttari M, Manninen V, Huttunen JK, Heinonen OP, Frick MH. Coronary heart disease incidence in NIDDM patients in the Helsinki heart study. Diabetes Care. 1992;15:820–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Patsch JR, Miesenbock G, Hopferwieser T, Muhlberger V, Knapp E, Dunn JK, Gotto AM, Jr., Patsch W. Relation of triglyceride metabolism and coronary artery disease: studies in the postprandial state. Arterioscler Thromb. 1992;12:1336–45.CrossRefPubMedGoogle Scholar
  13. 13.
    Kannel WB, Vasan RS. Triglycerides as vascular risk factors: new epidemiologic insights. Curr Opin Cardiol. 2009;24:345–50.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. J Am Med Assoc. 2007;298:299–308.CrossRefGoogle Scholar
  15. 15.
    Marfella R, Verrazzo G, Acampora R, La Marca C, Giunta R, Lucarelli C, Paolisso G, Ceriello A, Giugliano D. Glutathione reverses systemic hemodynamic changes by acute hyperglycemia in healthy subjects. Am J Physiol. 1995;268:E1167–73.PubMedGoogle Scholar
  16. 16.
    Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999;34:146–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Ceriello A, Cavarape A, Martinelli L, Da Ros R, Marra G, Quagliaro L, Piconi L, Assaloni R, Motz E. The post-prandial state in Type 2 diabetes and endothelial dysfunction: effects of insulin aspart. Diabet Med. 2004;21:171–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. 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. 2006;91:837–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation. 2005;112:179–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Scognamiglio R, Negut C, de Kreutzenberg SV, Tiengo A, Avogaro A. Effects of different insulin regimens on postprandial myocardial perfusion defects in type 2 diabetes patients. Diabetes Care. 2006;29:95–100.CrossRefPubMedGoogle Scholar
  21. 21.
    Ceriello A, Bortolotti N, Motz E, Pieri C, Marra M, Tonutti L, Lizzio S, Feletto F, Catone B, Taboga C. Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia. Metabolism. 1999;48:1503–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Borén J, Matikainen N, Adiels M, Taskinen MR. Postprandial hypertriglyceridemia as a coronary risk factor. Clin Chim Acta. 2014;431:131–42.CrossRefPubMedGoogle Scholar
  23. 23.
    Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, et al. Triglycerides and cardiovascular disease. Circulation. 2011;123:2292–33.CrossRefPubMedGoogle Scholar
  24. 24.
    Wang YI, Schulze J, Raymond N, Tomita T, Tam K, Simon SI, Passerini AG. Endothelial inflammation correlates with subject triglycerides and waist size after a high-fat meal. Am J Physiol Heart Circ Physiol. 2011;300:H784–91.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bae JH, Bassenge E, Kim KB, Kim YN, Kim KS, Lee HJ, Moon KC, Lee MS, Park KY, Schwemmer M. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis. 2001;155:517–53.CrossRefPubMedGoogle Scholar
  26. 26.
    Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79:350–4.CrossRefPubMedGoogle Scholar
  27. 27.
    Mano T, Masuyama T, Yamamoto K, Naito J, Kondo H, Nagano R, Tanouchi J, Hori M, Inoue M, Kamada T. Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound. Am Heart J. 1996;131:231–8.CrossRefPubMedGoogle Scholar
  28. 28.
    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 hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation. 2002;106:1211–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004;53:701–10.CrossRefPubMedGoogle Scholar
  30. 30.
    Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro L, 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;111:2518–24.CrossRefPubMedGoogle Scholar
  31. 31.
    Ristow M, Zarse K How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis) experimental. Gerontology. 2010;45:410–8.CrossRefGoogle Scholar
  32. 32.
    Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. 2011;51(2):327–36.CrossRefPubMedGoogle Scholar
  33. 33.
    Ristow M Unraveling the truth about antioxidants: mitohormesis explains ROS-induced health benefits. Nat Med. 2014;20:709–11.CrossRefPubMedGoogle Scholar
  34. 34.
    Lassègue B, San Martín A, Griendling KK Biochemistry, physiology and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res. 2012;110:1364–90.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Brownlee M Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–80.CrossRefPubMedGoogle Scholar
  36. 36.
    Giacco F, Du X, Carratú A, Gerfen GJ, D'Apolito M, Giardino I, Rasola A, Marin O, Divakaruni AS, Murphy AN, Shah MS, Brownlee M. GLP-1 cleavage product reverses persistent ROS generation after transient hyperglycemia by disrupting an ROS-generating feedback loop. Diabetes. 2015;64:3273–84.CrossRefPubMedGoogle Scholar
  37. 37.
    Piconi L, Quagliaro L, Da Ros R, et al. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemost. 2004;2(1):453–9.Google Scholar
  38. 38.
    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;52:2795–804.CrossRefPubMedGoogle Scholar
  39. 39.
    Quagliaro L, Piconi L, Assaloni R, 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;183:259–67.CrossRefPubMedGoogle Scholar
  40. 40.
    Piconi L, Quagliaro L, Assaloni R, et al. Constant and intermittent high glucose enhances endothelial cell apoptosis through mitochondrial superoxide overproduction. Diabetes Metab Res Rev. 2006;22:198–203.CrossRefPubMedGoogle Scholar
  41. 41.
    La Sala L, Pujadas G, De Nigris V, Canivell S, Novials A, Genovese S, Ceriello A. Oscillating glucose and constant high glucose induce endoglin expression in endothelial cells: the role of oxidative stress. Acta Diabetol. 2015;52:505–12.CrossRefPubMedGoogle Scholar
  42. 42.
    Otsuka A, Azuma K, Iesaki T, Sato F, Hirose T, Shimizu T, Tanaka Y, Daida H, Kawamori R, Watada H. Temporary hyperglycaemia provokes monocyte adhesion to endothelial cells in rat thoracic aorta. Diabetologia. 2005;48:2667–74.CrossRefPubMedGoogle Scholar
  43. 43.
    Azuma K, Kawamori R, Toyofuku Y, Kitahara Y, Sato F, Shimizu T, Miura K, Mine T, Tanaka Y, Mitsumata M, Watada H. Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol. 2006;26:2275–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Tanaka A, Azuma K, Toyofuku Y, et al. Insulin and nateglinide reduce monocyte adhesion to endothelial cells in goto-kakizaki rats exhibiting repetitive blood glucose fluctuation. Biochem Biophys Res Commun. 2006;350:195–201.CrossRefPubMedGoogle Scholar
  45. 45.
    Azuma K, Toyofuku Y, Iesaki T, et al. Acarbose, an α-glucosidase inhibitor, improves endothelial dysfunction in goto-kakizaki rats exhibiting repetitive blood glucose fluctuation. Biochem Biophys Res Commun. 2006;345:688–93.CrossRefPubMedGoogle Scholar
  46. 46.
    Wallace JP1, Johnson B, Padilla J, Mather K. Postprandial lipaemia, oxidative stress and endothelial function: a review. Int J Clin Pract. 2010; 64: 389–403Google Scholar
  47. 47.
    Fard A, Tuck CH, Donis JA, et al. 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;20:2039–44.CrossRefPubMedGoogle Scholar
  48. 48.
    Marchesi S, Lupattelli G, Schillaci G, Pirro M, Siepi D, Roscini AR, Pasqualini L, Mannarino E. Impaired flow-mediated vasoactivity during post-prandial phase in young healthy men. Atherosclerosis. 2000;153:397–402.CrossRefPubMedGoogle Scholar
  49. 49.
    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. J Am Med Assoc. 1997;278:1682–6.CrossRefGoogle Scholar
  50. 50.
    Fisher-Wellman KH, Bloomer RJ. Exacerbated postprandial oxidative stress induced by the acute intake of a lipid meal compared to isoenergetically administered carbohydrate, protein, and mixed meals in young, healthy men. J Am Coll Nutr. 2010;29:373–81.CrossRefPubMedGoogle Scholar
  51. 51.
    Gregersen S, Samocha-Bonet D, Heilbronn LK, Campbell LV. Inflammatory and oxidative stress responses to high-carbohydrate and high-fat meals in healthy humans. J Nutr Metab. 2012;2012:238056.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Saxena R, Madhu SV, Shukla R, Prabhu KM, Gambhir JK. Postprandial hypertriglyceridemia and oxidative stress in patients of type 2 diabetes mellitus with macrovascular complications. Clin Chim Acta. 2005;359:101–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Centro de Investigacion Biomèdica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM)BarcelonaSpain
  3. 3.Department of Cardiovascular and Metabolic DiseasesIRCCS MultimedicaMilanItaly

Personalised recommendations