Circulation. 2002;106:2067-2072
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
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:2067.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans
Role of Oxidative Stress
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.
Correspondence to Dario Giugliano, MD, Dept of Geriatrics and Metabolic Diseases, Policlinico della Seconda Università di Napoli, Piazza Miraglia, 80138 Napoli, Italy. E-mail dario.giugliano{at}unina2.it
Background— Circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-
(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.
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-, 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.
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.
Key Words: hyperglycemia • tumor necrosis factor • interleukins • glutathione
This article has been cited by other articles:
 |
|
 |
|
  P. Kallio, M. Kolehmainen, D. E Laaksonen, L. Pulkkinen, M. Atalay, H. Mykkanen, M. Uusitupa, K. Poutanen, and L. Niskanen Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1497 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Opie Metabolic Management of Acute Myocardial Infarction Comes to the Fore and Extends Beyond Control of Hyperglycemia Circulation, April 29, 2008; 117(17): 2172 - 2177. [Full Text] [PDF]
|
|
|
|
 |
|
 U. N. Das Risk of type 2 diabetes mellitus in those with hypertension Eur. Heart J., April 1, 2008; 29(7): 952 - 953. [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Nilsson, E. M. Ostman, J. J. Holst, and I. M. E. Bjorck Including Indigestible Carbohydrates in the Evening Meal of Healthy Subjects Improves Glucose Tolerance, Lowers Inflammatory Markers, and Increases Satiety after a Subsequent Standardized Breakfast J. Nutr., April 1, 2008; 138(4): 732 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Xiao, Y. Su, R. C. M. Simmen, and F. A. Simmen Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G868 - G876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Deedwania, M. Kosiborod, E. Barrett, A. Ceriello, W. Isley, T. Mazzone, and P. Raskin Hyperglycemia and Acute Coronary Syndrome: A Scientific Statement From the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism Circulation, March 25, 2008; 117(12): 1610 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C Nilsson, E. M Ostman, Y. Granfeldt, and I. M. Bjorck Effect of cereal test breakfasts differing in glycemic index and content of indigestible carbohydrates on daylong glucose tolerance in healthy subjects Am. J. Clinical Nutrition, March 1, 2008; 87(3): 645 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Collier, L. A. Dossett, A. K. May, and J. J. Diaz Glucose Control and the Inflammatory Response Nutr Clin Pract, February 1, 2008; 23(1): 3 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Giugliano, A. Ceriello, and K. Esposito Glucose metabolism and hyperglycemia Am. J. Clinical Nutrition, January 1, 2008; 87(1): 217S - 222S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chaudhuri, M. Miller, R. Nesto, N. Rosenberg, and P. Dandona Targeting Glucose in Acute Myocardial Infarction: Has glucose, insulin, and potassium infusion missed the target? Diabetes Care, December 1, 2007; 30(12): 3026 - 3028. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Qi, N. Rifai, and F. B. Hu Interleukin-6 Receptor Gene Variations, Plasma Interleukin-6 Levels, and Type 2 Diabetes in U.S. Women Diabetes, December 1, 2007; 56(12): 3075 - 3081. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Evans, M. Collins, C. Jennings, L. van der Merwe, I. Soderstrom, T. Olsson, N. S Levitt, E. V Lambert, and J. H Goedecke The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease Eur. J. Endocrinol., November 1, 2007; 157(5): 633 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Asadollahi, N. Beeching, and G. Gill Hyperglycaemia and mortality J R Soc Med, November 1, 2007; 100(11): 503 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patel, H. Ghanim, S. Ravishankar, C. L. Sia, P. Viswanathan, P. Mohanty, and P. Dandona Prolonged Reactive Oxygen Species Generation and Nuclear Factor-{kappa}B Activation after a High-Fat, High-Carbohydrate Meal in the Obese J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4476 - 4479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Brignardello, C. Runzo, M. Aragno, M. G. Catalano, M. Cassader, P. C. Perin, and G. Boccuzzi Dehydroepiandrosterone Administration Counteracts Oxidative Imbalance and Advanced Glycation End Product Formation in Type 2 Diabetic Patients Diabetes Care, November 1, 2007; 30(11): 2922 - 2927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Mita, H. Watada, T. Shimizu, Y. Tamura, F. Sato, T. Watanabe, J. B. Choi, T. Hirose, Y. Tanaka, and R. Kawamori Nateglinide Reduces Carotid Intima-Media Thickening in Type 2 Diabetic Patients Under Good Glycemic Control Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2456 - 2462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M Bruun, B. Stallknecht, J. W Helge, and B. Richelsen Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss Eur. J. Endocrinol., October 1, 2007; 157(4): 465 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. V. Ramana, R. Tammali, A. B. M. Reddy, A. Bhatnagar, and S. K. Srivastava Aldose Reductase-Regulated Tumor Necrosis Factor-{alpha} Production Is Essential for High Glucose-Induced Vascular Smooth Muscle Cell Growth Endocrinology, September 1, 2007; 148(9): 4371 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zirlik, S. M. Abdullah, N. Gerdes, L. MacFarlane, U. Schonbeck, A. Khera, D. K. McGuire, G. L. Vega, S. Grundy, P. Libby, et al. Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis: Results From the Dallas Heart Study Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 2043 - 2049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Varraso, T. T Fung, F. B Hu, W. Willett, and C. A Camargo Prospective study of dietary patterns and chronic obstructive pulmonary disease among US men Thorax, September 1, 2007; 62(9): 786 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-T. Lin-Tan, J.-L. Lin, L.-H. Wang, L.-M. Wang, L.-M. Huang, L. Liu, J.-Y. Huang, and Y.-L. Huang Fasting Glucose Levels in Predicting 1-Year All-Cause Mortality in Patients Who Do Not Have Diabetes and Are on Maintenance Hemodialysis J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2385 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Kitzmiller, L. Dang-Kilduff, and M. M. Taslimi Gestational Diabetes After Delivery: Short-term management and long-term risks Diabetes Care, July 1, 2007; 30(Supplement_2): S225 - S235. [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Zorrilla, M. Sanchez-Alavez, S. Sugama, M. Brennan, R. Fernandez, T. Bartfai, and B. Conti Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency PNAS, June 26, 2007; 104(26): 11097 - 11102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Niehoff, T. W. van Haeften, N. C. Onland-Moret, C. C. Elbers, C. Wijmenga, and Y. T. van der Schouw C-Reactive Protein Is Independently Associated With Glucose but Not With Insulin Resistance in Healthy Men Diabetes Care, June 1, 2007; 30(6): 1627 - 1629. [Full Text] [PDF]
|
|
|
|
|
|
H. Ghanim, P. Mohanty, R. Pathak, A. Chaudhuri, C. L. Sia, and P. Dandona Orange Juice or Fructose Intake Does Not Induce Oxidative and Inflammatory Response Diabetes Care, June 1, 2007; 30(6): 1406 - 1411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Baker, N. Clark, A. L. Brennan, D. A. Fisher, K. M. Gyi, M. E. Hodson, B. J. Philips, D. L. Baines, and D. M. Wood Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis J Appl Physiol, May 1, 2007; 102(5): 1969 - 1975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Katakami, H. Kaneto, M. Matsuhisa, K. Yoshiuchi, K. Kato, K. Yamamoto, Y. Umayahara, K. Kosugi, M. Hori, and Y. Yamasaki Serum Interleukin-18 Levels Are Increased and Closely Associated With Various Soluble Adhesion Molecule Levels in Type 1 Diabetic Patients Diabetes Care, January 1, 2007; 30(1): 159 - 161. [Full Text] [PDF]
|
|
|
|
|
|
M. Aragno, R. Mastrocola, C. Medana, M. G. Catalano, I. Vercellinatto, O. Danni, and G. Boccuzzi Oxidative Stress-Dependent Impairment of Cardiac-Specific Transcription Factors in Experimental Diabetes Endocrinology, December 1, 2006; 147(12): 5967 - 5974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Nettleton, L. J. Harnack, C. G. Scrafford, P. J. Mink, L. M. Barraj, and D. R. Jacobs Jr. Dietary Flavonoids and Flavonoid-Rich Foods Are Not Associated with Risk of Type 2 Diabetes in Postmenopausal Women J. Nutr., December 1, 2006; 136(12): 3039 - 3045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gyurko, C. C. Siqueira, N. Caldon, L. Gao, A. Kantarci, and T. E. Van Dyke Chronic Hyperglycemia Predisposes to Exaggerated Inflammatory Response and Leukocyte Dysfunction in Akita Mice J. Immunol., November 15, 2006; 177(10): 7250 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishihara, I. Inoue, T. Kawagoe, Y. Shimatani, S. Kurisu, T. Hata, Y. Nakama, Y. Kijima, and E. Kagawa Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance? Eur. Heart J., October 2, 2006; 27(20): 2413 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Devaraj, B. C Autret, and I. Jialal Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 756 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. A. Smit and J. A. Romijn Acute insulin resistance in myocardial ischemia: causes and consequences. Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2006; 10(3): 215 - 219. [Abstract] [PDF]
|
|
|
|
|
|
H. B. Van Wezel Glucose-insulin-potassium techniques in cardiac surgery: historical overview and future perspectives. Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2006; 10(3): 224 - 227. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Giugliano, A. Ceriello, and K. Esposito The Effects of Diet on Inflammation: Emphasis on the Metabolic Syndrome J. Am. Coll. Cardiol., August 15, 2006; 48(4): 677 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Esposito and D. Giugliano Whole-grain intake cools down inflammation Am. J. Clinical Nutrition, June 1, 2006; 83(6): 1440 - 1441. [Full Text] [PDF]
|
|
|
|
|
|
B. Okopien, R. Krysiak, and Z. S. Herman Effects of Short-Term Fenofibrate Treatment on Circulating Markers of Inflammation and Hemostasis in Patients with Impaired Glucose Tolerance J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1770 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Starkey, S. J. Haidacher, W. S. LeJeune, X. Zhang, B. C. Tieu, S. Choudhary, A. R. Brasier, L. A. Denner, and R. G. Tilton Diabetes-Induced Activation of Canonical and Noncanonical Nuclear Factor-{kappa}B Pathways in Renal Cortex. Diabetes, May 1, 2006; 55(5): 1252 - 1259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. de Jager, J. M. Dekker, A. Kooy, P. J. Kostense, G. Nijpels, R. J. Heine, L. M. Bouter, and C. D.A. Stehouwer Endothelial Dysfunction and Low-Grade Inflammation Explain Much of the Excess Cardiovascular Mortality in Individuals With Type 2 Diabetes: The Hoorn Study Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1086 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Galassetti, K. Iwanaga, A. M. Pontello, F. P. Zaldivar, R. L. Flores, and J. K. Larson Effect of prior hyperglycemia on IL-6 responses to exercise in children with type 1 diabetes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E833 - E839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-a Kim, M. Montagnani, K. K. Koh, and M. J. Quon Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms Circulation, April 18, 2006; 113(15): 1888 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E Kasim-Karakas, A. Tsodikov, U. Singh, and I. Jialal Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake. Am. J. Clinical Nutrition, April 1, 2006; 83(4): 774 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Srivastava, K. V. Ramana, R. Tammali, S. K. Srivastava, and A. Bhatnagar Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells. Diabetes, April 1, 2006; 55(4): 901 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Arimura, M. Li, V. Batuman, W.F. Clark, A.K. Stewart, G.A. Rock, M. Sternbach, D.M. Sutton, B.J. Barrett, A.P. Heidenheim, et al. Cast Nephropathy in Myeloma--Does PACAP38, a New Member of the Vasoactive Intestinal Peptide Family, Open a Therapeutic Window?: Potential Protective Action of Pituitary Adenylate Cyclase-Activiating Polypeptide (PACAP38) on In Vitro and In Vivo Models of Myeloma Kidney Injury. Blood 107: 661-668, 2006 J. Am. Soc. Nephrol., April 1, 2006; 17(4): 911 - 919. [Full Text] [PDF]
|
|
|
|
 |
|
 J.R. Timmer, J.P. Ottervanger, H.J.G. Bilo, J.H.E. Dambrink, K. Miedema, J.C.A. Hoorntje, and F. Zijlstra Prognostic value of admission glucose and glycosylated haemoglobin levels in acute coronary syndromes QJM, April 1, 2006; 99(4): 237 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Santilli, G. Davi, A. Consoli, F. Cipollone, A. Mezzetti, A. Falco, T. Taraborelli, E. Devangelio, G. Ciabattoni, S. Basili, et al. Thromboxane-Dependent CD40 Ligand Release in Type 2 Diabetes Mellitus J. Am. Coll. Cardiol., January 17, 2006; 47(2): 391 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Esposito and D. Giugliano Diet and inflammation: a link to metabolic and cardiovascular diseases Eur. Heart J., January 1, 2006; 27(1): 15 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakamura, K. Shikata, M. Hiramatsu, T. Nakatou, T. Kitamura, J. Wada, T. Itoshima, and H. Makino Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes Diabetes Care, December 1, 2005; 28(12): 2890 - 2895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, C. E. Robert, B. R. Burkhardt, R. A. Young, J. Wu, Z. Gao, and B. A. Wolf Mechanisms of Glucose-Induced Secretion of Pancreatic-Derived Factor (PANDER or FAM3B) in Pancreatic {beta}-Cells Diabetes, November 1, 2005; 54(11): 3217 - 3228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Song, J. E. Manson, J. E. Buring, H. D. Sesso, and S. Liu Associations of Dietary Flavonoids with Risk of Type 2 Diabetes, and Markers of Insulin Resistance and Systemic Inflammation in Women: A Prospective Study and Cross-Sectional Analysis J. Am. Coll. Nutr., October 1, 2005; 24(5): 376 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Cheung, B. Napier, C. Zaccaria, and J. P. Fletcher Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition Diabetes Care, October 1, 2005; 28(10): 2367 - 2371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|