on September 30, 2002
Circulation. 2002
Published online before print September 30, 2002, doi: 10.1161/01.CIR.0000034509.14906.AE
Published online before print September 30, 2002, doi: 10.1161/01.CIR.0000034509.14906.AE
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Submitted on June 17, 2002
From the Department of Geriatric and Metabolic Diseases (K.E., F.N., R.M., G.G., F.G., M.C., D.G.) and Cardiovascular Research Centre (R.M., D.G.), Second University of Naples; and Chair of Internal Medicine (A.C., L.Q.), University of Udine, Italy * To whom correspondence should be addressed. E-mail: dario.giugliano{at}unina2.it.
Background—Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor- Methods and Results—Plasma glucose levels were acutely raised in 20 control and 15 IGT subjects and maintained at 15 mmol/L for 5 hours while endogenous insulin secretion was blocked with octreotide. In control subjects, plasma IL-6, TNF- Conclusions—Hyperglycemia acutely increases circulating cytokine concentrations by an oxidative mechanism, and this effect is more pronounced in subjects with IGT. This suggests a causal role for hyperglycemia in the immune activation of diabetes.
Revised on August 2, 2002
Accepted on August 5, 2002
Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans. Role of Oxidative Stress
Katherine Esposito MD,
(TNF-) are elevated in diabetic patients. We assessed the role of glucose in the regulation of circulating levels of IL-6, TNF-, and interleukin-18 (IL-18) in subjects with normal or impaired glucose tolerance (IGT), as well as the effect of the antioxidant glutathione., and IL-18 levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In another study, the same subjects received 3 consecutive pulses of intravenous glucose (0.33 g/kg) separated by a 2-hour interval. Plasma cytokine levels obtained at 3, 4, and 5 hours were higher (P<0.05) than the corresponding values obtained during the clamp. The IGT subjects had fasting plasma IL-6 and TNF- levels higher (P<0.05) than those of control subjects. The increase in plasma cytokine levels during the clamping lasted longer (4 hours versus 2 hours, P<0.01) in the IGT subjects than in the control subjects, and the cytokine peaks of IGT subjects after the first glucose pulse were higher (P<0.05) than those of control subjects. On another occasion, 10 control and 8 IGT subjects received the same glucose pulses as above during an infusion of glutathione; plasma cytokine levels did not show any significant change from baseline after the 3 glucose pulses.
Key words: hyperglycemia • tumor necrosis factor • interleukins • glutathione
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 L. Visser, C. J. Zuurbier, F. J. Hoek, B. C. Opmeer, E. de Jonge, B. A. J. M. de Mol, and H. B. van Wezel Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery Br. J. Anaesth., October 1, 2005; 95(4): 448 - 457. [Abstract] [Full Text] [PDF]
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A. T Merchant, G. C Curhan, E. B Rimm, W. C Willett, and W. W Fawzi Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men Am. J. Clinical Nutrition, September 1, 2005; 82(3): 668 - 674. [Abstract] [Full Text] [PDF]
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Y. Kataoka, S. Yasuda, I. Morii, Y. Otsuka, A. Kawamura, and S. Miyazaki Quantitative Coronary Angiographic Studies of Patients With Angina Pectoris and Impaired Glucose Tolerance Diabetes Care, September 1, 2005; 28(9): 2217 - 2222. [Abstract] [Full Text] [PDF]
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B J Philips, J Redman, A Brennan, D Wood, R Holliman, D Baines, and E H Baker Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients Thorax, September 1, 2005; 60(9): 761 - 764. [Abstract] [Full Text] [PDF]
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C. S. Mantzoros, T. Li, J. E. Manson, J. B. Meigs, and F. B. Hu Circulating Adiponectin Levels Are Associated with Better Glycemic Control, More Favorable Lipid Profile, and Reduced Inflammation in Women with Type 2 Diabetes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4542 - 4548. [Abstract] [Full Text] [PDF]
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B. Capaldo, M. Galderisi, A. A. Turco, A. D'Errico, S. Turco, A. A. Rivellese, G. de Simone, O. de Divitiis, and G. Riccardi Acute Hyperglycemia Does Not Affect the Reactivity of Coronary Microcirculation in Humans J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3871 - 3876. [Abstract] [Full Text] [PDF]
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I. Shai, M. B. Schulze, J. E. Manson, K. M. Rexrode, M. J. Stampfer, C. Mantzoros, and F. B. Hu A Prospective Study of Soluble Tumor Necrosis Factor-{alpha} Receptor II (sTNF-RII) and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes Diabetes Care, June 1, 2005; 28(6): 1376 - 1382. [Abstract] [Full Text] [PDF]
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J. Hung, B. M. McQuillan, C. M. L. Chapman, P. L. Thompson, and J. P. Beilby Elevated Interleukin-18 Levels Are Associated With the Metabolic Syndrome Independent of Obesity and Insulin Resistance Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1268 - 1273. [Abstract] [Full Text] [PDF]
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A. Ceriello, R. Assaloni, R. Da Ros, A. Maier, L. Piconi, L. Quagliaro, K. Esposito, and D. Giugliano Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients Circulation, May 17, 2005; 111(19): 2518 - 2524. [Abstract] [Full Text] [PDF]
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J. R. Timmer, J. P. Ottervanger, M.-J. de Boer, J.-H. E. Dambrink, J. C.A. Hoorntje, A.T. M. Gosselink, H. Suryapranata, F. Zijlstra, A. W.J. van't Hof, and Zwolle Myocardial Infarction Study Group Hyperglycemia is an important predictor of impaired coronary flow before reperfusion therapy in ST-segment elevation myocardial infarction J. Am. Coll. Cardiol., April 5, 2005; 45(7): 999 - 1002. [Abstract] [Full Text] [PDF]
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A. Rozanski, J. A. Blumenthal, K. W. Davidson, P. G. Saab, and L. Kubzansky The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: The emerging field of behavioral cardiology J. Am. Coll. Cardiol., March 1, 2005; 45(5): 637 - 651. [Abstract] [Full Text] [PDF]
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A. Ceriello Acute hyperglycaemia: a 'new' risk factor during myocardial infarction Eur. Heart J., February 2, 2005; 26(4): 328 - 331. [Abstract] [Full Text] [PDF]
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 R. A. Zager, A. C. M. Johnson, S. Y. Hanson, and S. Lund Parenteral iron compounds sensitize mice to injury-initiated TNF-{alpha} mRNA production and TNF-{alpha} release Am J Physiol Renal Physiol, February 1, 2005; 288(2): F290 - F297. [Abstract] [Full Text] [PDF]
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A. Ceriello Postprandial Hyperglycemia and Diabetes Complications: Is It Time to Treat? Diabetes, January 1, 2005; 54(1): 1 - 7. [Abstract] [Full Text] [PDF]
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 M E Tushuizen, M Diamant, and R J Heine Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes Postgrad. Med. J., January 1, 2005; 81(951): 1 - 6. [Abstract] [Full Text] [PDF]
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 L. A Powell, K. M Warpeha, W. Xu, B. Walker, and E. R Trimble High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells J. Mol. Endocrinol., December 1, 2004; 33(3): 797 - 803. [Abstract] [Full Text] [PDF]
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V. W. Wong, M. McLean, S. C. Boyages, and N. W. Cheung C-Reactive Protein Levels Following Acute Myocardial Infarction: Effect of insulin infusion and tight glycemic control Diabetes Care, December 1, 2004; 27(12): 2971 - 2973. [Full Text] [PDF]
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A. Ceriello Insulin, Glycemic Control, and C-Reactive Protein During Myocardial Infarction Diabetes Care, December 1, 2004; 27(12): 3017 - 3018. [Full Text] [PDF]
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P. J. Manning, W. H. Sutherland, G. Hendry, S. A. de Jong, M. McGrath, and S. M. Williams Changes in Circulating Postprandial Proinflammatory Cytokine Concentrations in Diet-Controlled Type 2 Diabetes and the Effect of Ingested Fat Diabetes Care, October 1, 2004; 27(10): 2509 - 2511. [Full Text] [PDF]
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H. Ghanim, A. Aljada, D. Hofmeyer, T. Syed, P. Mohanty, and P. Dandona Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State Circulation, September 21, 2004; 110(12): 1564 - 1571. [Abstract] [Full Text] [PDF]
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Z. T. Bloomgarden Inpatient Diabetes Control: Approaches to treatment Diabetes Care, September 1, 2004; 27(9): 2272 - 2277. [Full Text] [PDF]
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D. Han, X. Xu, D. Baidal, J. Leith, C. Ricordi, R. Alejandro, and N. S. Kenyon Assessment of Cytotoxic Lymphocyte Gene Expression in the Peripheral Blood of Human Islet Allograft Recipients: Elevation Precedes Clinical Evidence of Rejection Diabetes, September 1, 2004; 53(9): 2281 - 2290. [Abstract] [Full Text] [PDF]
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A. E. Caballero, A. Delgado, C. A. Aguilar-Salinas, A. N. Herrera, J. L. Castillo, T. Cabrera, F. J. Gomez-Perez, and J. A. Rull The Differential Effects of Metformin on Markers of Endothelial Activation and Inflammation in Subjects with Impaired Glucose Tolerance: A Placebo-Controlled, Randomized Clinical Trial J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3943 - 3948. [Abstract] [Full Text] [PDF]
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K. Esposito, D. Giugliano, F. Nappo, R. Marfella, and for the Campanian Postprandial Hyperglycemia Study Regression of Carotid Atherosclerosis by Control of Postprandial Hyperglycemia in Type 2 Diabetes Mellitus Circulation, July 13, 2004; 110(2): 214 - 219. [Abstract] [Full Text] [PDF]
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M. B. Schulze, E. B. Rimm, I. Shai, N. Rifai, and F. B. Hu Relationship Between Adiponectin and Glycemic Control, Blood Lipids, and Inflammatory Markers in Men With Type 2 Diabetes Diabetes Care, July 1, 2004; 27(7): 1680 - 1687. [Abstract] [Full Text] [PDF]
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A. Ceriello and E. Motz Is Oxidative Stress the Pathogenic Mechanism Underlying Insulin Resistance, Diabetes, and Cardiovascular Disease? The Common Soil Hypothesis Revisited Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 816 - 823. [Abstract] [Full Text]
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R. Krogh-Madsen, K. Moller, F. Dela, G. Kronborg, S. Jauffred, and B. K. Pedersen Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-{alpha}, and FFAs to low-dose endotoxemia in humans Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E766 - E772. [Abstract] [Full Text] [PDF]
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