This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katsuki, A. Articles by Yano, Y. Search for Related Content PubMed PubMed Citation Articles by Katsuki, A. Articles by Yano, Y.

Serum Levels of Tumor Necrosis Factor- Are Increased in Obese Patients with Noninsulin-Dependent Diabetes Mellitus¹

Third Department of Internal Medicine (A.K., Y.S., K.I., M.F., K.T., H.G., K.N., Y.Y.) and Department of Radiology (S.M.), Mie University School of Medicine; Department of Internal Medicine (K.M., Y.T.), Yamada Red Cross Hospital, Mie, Japan

Address correspondence and requests for reprints to: Akira Katsuki, M.D., Third Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514, Japan.

To clarify the significance of the serum levels of tumor necrosis factor- (TNF-) in the mechanism of insulin resistance, we studied 12 obese patients with noninsulin-dependent diabetes mellitus (NIDDM). We evaluated the relationship of TNF- levels with the visceral, subcutaneous, and total fat areas measured by computed tomography (CT), and with insulin resistance evaluated by the glucose infusion rate (GIR) observed during an euglycemic hyperinsulinemic clamp study. Controls consisted of 12 normal subjects and 12 nonobese patients with NIDDM. TNF- levels were measured using a high sensitivity enzyme-linked immunosorbent assay. Following admission, all patients with NIDDM participated in a 4-week program of diet and exercise. After this treatment, we evaluated the relationship of the serum levels of TNF- with the area of body fat, the GIR, and the resultant change in the TNF- level.

Serum levels of TNF- in the obese patients with NIDDM significantly exceeded those observed in normal subjects (P < 0.01) or in the nonobese patients with NIDDM (P < 0.01). Serum levels of TNF- in obese NIDDM patients showed a significant positive correlation with the area of visceral fat before (r = 0.662, P < 0.03) and after (r = 0.508, P < 0.05) the treatment; similar correlation was observed in all patients with NIDDM before (r = 0.537, P < 0.02) and after (r = 0.430, P < 0.05) the treatment. Serum levels of TNF- in obese NIDDM patients showed a significant negative correlation with GIR after the treatment (r = -0.595, P < 0.05). Serum levels of TNF- were significantly reduced in the obese patients with NIDDM after the treatment (P < 0.01), while those in the nonobese NIDDM patients were unchanged.

These results suggest that serum TNF- levels may play an important role in mechanism of insulin resistance associated with obesity.

This article has been cited by other articles:

				S. S Lund, L. Tarnow, C. D A Stehouwer, C. G Schalkwijk, T. Teerlink, J. Gram, K. Winther, M. Frandsen, U. M Smidt, O. Pedersen, et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes Eur. J. Endocrinol., May 1, 2008; 158(5): 631 - 641. [Abstract] [Full Text] [PDF]

				M. C. Cave, R. T. Hurt, T. H. Frazier, P. J. Matheson, R. N. Garrison, C. J. McClain, and S. A. McClave Obesity, Inflammation, and the Potential Application of Pharmaconutrition Nutr Clin Pract, February 1, 2008; 23(1): 16 - 34. [Abstract] [Full Text] [PDF]

				R. Krogh-Madsen, P. Plomgaard, T. Akerstrom, K. Moller, O. Schmitz, and B. K. Pedersen Effect of short-term intralipid infusion on the immune response during low-dose endotoxemia in humans Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E371 - E379. [Abstract] [Full Text] [PDF]

				L. M. Bell, K. Watts, A. Siafarikas, A. Thompson, N. Ratnam, M. Bulsara, J. Finn, G. O'Driscoll, D. J. Green, T. W. Jones, et al. Exercise Alone Reduces Insulin Resistance in Obese Children Independently of Changes in Body Composition J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4230 - 4235. [Abstract] [Full Text] [PDF]

				E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]

				R. Krogh-Madsen, P. Plomgaard, K. Moller, B. Mittendorfer, and B. K. Pedersen Influence of TNF-{alpha} and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E108 - E114. [Abstract] [Full Text] [PDF]

				L. Wang, X.-P. Xing, A. Holmes, C. Wadham, J. R. Gamble, M. A. Vadas, and P. Xia Activation of the Sphingosine Kinase-Signaling Pathway by High Glucose Mediates the Proinflammatory Phenotype of Endothelial Cells Circ. Res., October 28, 2005; 97(9): 891 - 899. [Abstract] [Full Text] [PDF]

				J. F. Navarro, C. Mora, M. Muros, and J. Garcia Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade: A Short-Term, Randomized, Controlled Trial J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2119 - 2126. [Abstract] [Full Text] [PDF]

				A. Kosaki, T. Hasegawa, T. Kimura, K. Iida, J. Hitomi, H. Matsubara, Y. Mori, M. Okigaki, N. Toyoda, H. Masaki, et al. Increased Plasma S100A12 (EN-RAGE) Levels in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5423 - 5428. [Abstract] [Full Text] [PDF]

				H. Lu, M. Raptis, E. Black, M. Stan, S. Amar, and D. T. Graves Influence of Diabetes on the Exacerbation of an Inflammatory Response in Cardiovascular Tissue Endocrinology, November 1, 2004; 145(11): 4934 - 4939. [Abstract] [Full Text] [PDF]

				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]

				D. B. Carr, K. M. Utzschneider, R. L. Hull, K. Kodama, B. M. Retzlaff, J. D. Brunzell, J. B. Shofer, B. E. Fish, R. H. Knopp, and S. E. Kahn Intra-Abdominal Fat Is a Major Determinant of the National Cholesterol Education Program Adult Treatment Panel III Criteria for the Metabolic Syndrome Diabetes, August 1, 2004; 53(8): 2087 - 2094. [Abstract] [Full Text] [PDF]

				M. T. Coughlan, M. Permezel, H. M. Georgiou, and G. E. Rice Repression of Oxidant-Induced Nuclear Factor-{kappa}B Activity Mediates Placental Cytokine Responses in Gestational Diabetes J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3585 - 3594. [Abstract] [Full Text] [PDF]

				J. N. Fain, A. K. Madan, M. L. Hiler, P. Cheema, and S. W. Bahouth Comparison of the Release of Adipokines by Adipose Tissue, Adipose Tissue Matrix, and Adipocytes from Visceral and Subcutaneous Abdominal Adipose Tissues of Obese Humans Endocrinology, May 1, 2004; 145(5): 2273 - 2282. [Abstract] [Full Text] [PDF]

				J. C. Pickup Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes Diabetes Care, March 1, 2004; 27(3): 813 - 823. [Abstract] [Full Text] [PDF]

				R. Krogh-Madsen, P. Plomgaard, P. Keller, C. Keller, and B. K. Pedersen Insulin stimulates interleukin-6 and tumor necrosis factor-{alpha} gene expression in human subcutaneous adipose tissue Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E234 - E238. [Abstract] [Full Text] [PDF]

				M. Wolf, J. Sauk, A. Shah, K. Vossen Smirnakis, R. Jimenez-Kimble, J. L. Ecker, and R. Thadhani Inflammation and Glucose Intolerance: A prospective study of gestational diabetes mellitus Diabetes Care, January 1, 2004; 27(1): 21 - 27. [Abstract] [Full Text] [PDF]

				T. Radaelli, A. Varastehpour, P. Catalano, and S. Hauguel-de Mouzon Gestational Diabetes Induces Placental Genes for Chronic Stress and Inflammatory Pathways Diabetes, December 1, 2003; 52(12): 2951 - 2958. [Abstract] [Full Text] [PDF]

				A. Katsuki, Y. Sumida, H. Urakawa, E. C. Gabazza, S. Murashima, N. Maruyama, K. Morioka, K. Nakatani, Y. Yano, and Y. Adachi Increased Visceral Fat and Serum Levels of Triglyceride Are Associated With Insulin Resistance in Japanese Metabolically Obese, Normal Weight Subjects With Normal Glucose Tolerance Diabetes Care, August 1, 2003; 26(8): 2341 - 2344. [Abstract] [Full Text] [PDF]

				A. Steensberg, C. P. Fischer, C. Keller, K. Moller, and B. K. Pedersen IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E433 - E437. [Abstract] [Full Text] [PDF]

				G. Amato, M. Conte, G. Mazziotti, E. Lalli, G. Vitolo, A. T. Tucker, A. Bellastella, C. Carella, and A. Izzo Serum and Follicular Fluid Cytokines in Polycystic Ovary Syndrome During Stimulated Cycles Obstet. Gynecol., June 1, 2003; 101(6): 1177 - 1182. [Abstract] [Full Text] [PDF]

				G. D. Slade, E. M. Ghezzi, G. Heiss, J. D. Beck, E. Riche, and S. Offenbacher Relationship Between Periodontal Disease and C-Reactive Protein Among Adults in the Atherosclerosis Risk in Communities Study Arch Intern Med, May 26, 2003; 163(10): 1172 - 1179. [Abstract] [Full Text] [PDF]

				M. Friedberg, E. Zoumakis, N. Hiroi, T. Bader, G. P. Chrousos, and Z.'e. Hochberg Modulation of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Mature Human Subcutaneous Adipocytes by Hypothalamic Messengers J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 385 - 393. [Abstract] [Full Text] [PDF]

				J.A. Paniagua, J. Lopez-Miranda, A. Escribano, F.J. Berral, C. Marin, D. Bravo, E. Paz-Rojas, P. Gomez, M. Barcos, J.A. Moreno, et al. Cerivastatin Improves Insulin Sensitivity and Insulin Secretion in Early-State Obese Type 2 Diabetes Diabetes, August 1, 2002; 51(8): 2596 - 2603. [Abstract] [Full Text] [PDF]

				M. Soop, H. Duxbury, A. O Agwunobi, J. M. Gibson, S. J. Hopkins, C. Childs, R. G. Cooper, P. Maycock, R. A. Little, and G. L. Carlson Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1276 - E1285. [Abstract] [Full Text] [PDF]

				A. P. Richardson and J. A. Tayek Type 2 diabetic patients may have a mild form of an injury response: a clinical research center study Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1286 - E1290. [Abstract] [Full Text] [PDF]

				T. Wu, J. P. Dorn, R. P. Donahue, C. T. Sempos, and M. Trevisan Associations of Serum C-reactive Protein with Fasting Insulin, Glucose, and Glycosylated Hemoglobin : The Third National Health and Nutrition Examination Survey, 1988-1994 Am. J. Epidemiol., January 1, 2002; 155(1): 65 - 71. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, R. M. Calvo, J. Sancho, and J. L. San Millan TNF-{alpha} and Hyperandrogenism: A Clinical, Biochemical, and Molecular Genetic Study J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3761 - 3767. [Abstract] [Full Text] [PDF]

				C. B. Whorwood, S. J. Donovan, P. J. Wood, and D. I. W. Phillips Regulation of Glucocorticoid Receptor {{alpha}} and {beta} Isoforms and Type I 11{beta}-Hydroxysteroid Dehydrogenase Expression in Human Skeletal Muscle Cells: A Key Role in the Pathogenesis of Insulin Resistance? J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2296 - 2308. [Abstract] [Full Text]

				J. M. Bruun, S. B. Pedersen, and B. Richelsen Regulation of Interleukin 8 Production and Gene Expression in Human Adipose Tissue in Vitro J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1267 - 1273. [Abstract] [Full Text]

				A. Katsuki, Y. Sumida, E. C. Gabazza, S. Murashima, M. Furuta, R. Araki-Sasaki, Y. Hori, Y. Yano, and Y. Adachi Homeostasis Model Assessment Is a Reliable Indicator of Insulin Resistance During Follow-up of Patients With Type 2 Diabetes Diabetes Care, February 1, 2001; 24(2): 362 - 365. [Abstract] [Full Text]

				C. G. Solomon and E. W. Seely Brief Review: Hypertension in Pregnancy : A Manifestation of the Insulin Resistance Syndrome? Hypertension, February 1, 2001; 37(2): 232 - 239. [Abstract] [Full Text] [PDF]

				B. B. Yaspelkis III, J. R. Davis, M. Saberi, T. L. Smith, R. Jazayeri, M. Singh, V. Fernandez, B. Trevino, N. Chinookoswong, J. Wang, et al. Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E130 - E142. [Abstract] [Full Text] [PDF]

				T. Rönnemaa, K. Pulkki, and J. Kaprio Serum Soluble Tumor Necrosis Factor-{alpha} Receptor 2 Is Elevated in Obesity But Is Not Related to Insulin Sensitivity: A Study in Identical Twins Discordant for Obesity J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2728 - 2732. [Abstract] [Full Text]

				N. Paquot, M. J. Castillo, P. J. Lefèbvre, and A. J. Scheen No Increased Insulin Sensitivity after a Single Intravenous Administration of a Recombinant Human Tumor Necrosis Factor Receptor: Fc Fusion Protein in Obese Insulin-Resistant Patients J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1316 - 1319. [Abstract] [Full Text]

				A. E. Hak, C. D. A. Stehouwer, M. L. Bots, K. H. Polderman, C. G. Schalkwijk, I. C. D. Westendorp, A. Hofman, and J. C. M. Witteman Associations of C-Reactive Protein With Measures of Obesity, Insulin Resistance, and Subclinical Atherosclerosis in Healthy, Middle-Aged Women Arterioscler. Thromb. Vasc. Biol., August 1, 1999; 19(8): 1986 - 1991. [Abstract] [Full Text] [PDF]

				T. Sakamoto, J. Woodcock-Mitchell, K. Marutsuka, J. J. Mitchell, B. E. Sobel, and S. Fujii TNF-alpha and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes Am J Physiol Cell Physiol, June 1, 1999; 276(6): C1391 - C1397. [Abstract] [Full Text] [PDF]

				K. T. Uysal, S. M. Wiesbrock, and G. S. Hotamisligil Functional Analysis of Tumor Necrosis Factor (TNF) Receptors in TNF-{alpha}-Mediated Insulin Resistance in Genetic Obesity Endocrinology, December 1, 1998; 139(12): 4832 - 4838. [Abstract] [Full Text] [PDF]