Download PDF
Horm Metab Res 2005; 37(10): 617-621
DOI: 10.1055/s-2005-870536
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Soluble TNF Receptors and Albuminuria in Non-obese Japanese Type 2 Diabetic Patients

Y.  Kawasaki1 , A.  Taniguchi2 , M.  Fukushima3 , Y.  Nakai4 , A.  Kuroe2 , M.  Ohya2 , S.  Nagasaka5 , Y.  Yamada1 , N.  Inagaki1 , Y.  Seino1, 2
  • 1Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • 2Division of Diabetes and Clinical Nutrition, Kansai-Denryoku Hospital, Osaka, Japan
  • 3Department of Health Informatics Research, Translational Research Informatics Center, Foundation for Biochemical Research and Innovation, Kobe, Japan
  • 4School of Health Sciences Faculty of Medicine, Kyoto University, Kyoto, Japan
  • 5Division of Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan
Further Information

Publication History

Received 17 December 2004

Accepted after revision 7 April 2005

Publication Date:
08 November 2005 (online)

Also available at
    Permissions and Reprints

Abstract

The aim of this study was to investigate the relationships between albuminuria and tumor necrosis factor (TNF)-α or soluble TNF receptors (sTNF-R1, sTNF-R2) in eighty-eight non-obese Japanese type 2 diabetic patients stratified into two groups according to albuminuria status-microalbuminuria or normoalbuminuria. Patients with microalbuminuria were older and had significantly higher concentrations of sTNF-R1 and sTNF-R2 than those with normoalbuminuria. There was, however, no significant difference in sex, diabetes duration, smoking, BMI, systolic and diastolic blood pressure, HbA1c, serum creatinine, and lipid profile between the two groups. Although serum TNF-α was positively correlated to serum sTNF-R1 and sTNF-R2, serum TNF-α level did not differ with respect to albuminuria. Univariate regression analysis showed that urinary albumin concentration was positively correlated to age (r = 0.380, p < 0.001), serum creatinine (r = 0.214, p < 0.05) and concentrations of sTNF-R1 (r = 0.364, p < 0.001) and sTNF-R2 (r = 0.342, p < 0.005). Other variables, including TNF-α, were not associated with albuminuria. Multiple regression analyses showed that urinary albumin concentration was independently predicted by the level of sTNF-R1 (F = 32.1), which explained 26.3 % of the variability of urinary albumin concentration. From these results, it can be concluded that serum soluble TNF receptor is an important independent factor associated with albuminuria in non-obese Japanese type 2 diabetic patients.

Key words

sTNF receptors - TNF-alpha - Albuminuria - Diabetes

  • 1 Fuller H, Shipley M J, Rose G, Jarrett R J, Keen H. Coronary heart disease risk and impaired glucose tolerance.  Lancet. 1980;  1 1373-1376
    PubMedGoogle Scholar
  • 2 Yano K, Kagan A, McGee D, Rhoads G G. Glucose intolerance and nine-year mortality in Japanese men in Hawaii.  Am J Med. 1982;  72 71-80
    CrossrefPubMedGoogle Scholar
  • 3 Diabetes Drafting Group . Prevalence of small vessel and large vessel disease in diabetic persons from 14 centers: the World Health Organization multinational study of vascular disease in diabetics.  Diabetologia. 1985;  28 615-640
    CrossrefPubMedGoogle Scholar
  • 4 Herman J B, Medalie J H, Goldbourt U. Differences in cardiovascular morbidity and mortality between previously known and newly diagnosed adult diabetics.  Diabetologia. 1977;  13 229-234
    CrossrefPubMedGoogle Scholar
  • 5 Mogensen C E. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.  N Engl J Med. 1984;  310 356-360
    PubMedGoogle Scholar
  • 6 Festa A, D’Agostino R, Howard G, Mykkanen L, Tracy R P, Haffner S M. Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The insulin resistance atherosclerosis study.  Kidney Int. 2000;  58 1703-1710
    CrossrefPubMedGoogle Scholar
  • 7 Stehouwer C DA, Gall M A, Twisk J WR, Knudsen E, Emeis J J, Parving H H. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes. Progressive, interrelated, and independently associated with risk of death.  Diabetes. 2002;  51 1157-1165
    CrossrefPubMedGoogle Scholar
  • 8 Smith C A, Farrah T, Goodwin R G. TNF receptor superfamily of cellular and viral proteins: activation, costimulation and death.  Cell. 1994;  76 959-962
    CrossrefPubMedGoogle Scholar
  • 9 Tartaglia L A, Weber R F, Figari I S, Reynolds S, Pailadino M A Jr, Goeddel D V. The two different receptors.  Proc Natl Acad Sci USA. 1991;  88 9292-9296
    PubMedGoogle Scholar
  • 10 Tartaglia L A, Goeddel D V. Two TNF receptors.  Immunol Today. 1992;  13 151-153
    CrossrefPubMedGoogle Scholar
  • 11 Rauchhaus M, Doehner W, Francis D P, Davos C, Kemp M, Liebenthal C, Niebauer J, Hooper J, Volk H D, Coats A JS, Anker S D. Plasma cytokine parameters and mortality in patients with chronic heart failure.  Circulation. 2000;  102 3060-3067
    PubMedGoogle Scholar
  • 12 Zoppini G, Faccini G, Muggeo M, Zenari L, Falezza G, Targher G. Elevated plasma levels of soluble receptors of TNF-α and their association with smoking and microvascular complications in young adults with type 1 diabetes.  J Clin Endocrinol Metab. 2001;  186 3805-3808
    PubMedGoogle Scholar
  • 13 Hotamisligil G S, Shargil N S, Spiegelman B M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.  Science. 1993;  259 87-91
    CrossrefPubMedGoogle Scholar
  • 14 Tanaka S, Seino H, Satoh J, Fujii N, Rikiishi H, Zhu X P, Takahashi K, Sagara M, Nobunaga T, Toyota T. Increased in vivo production of tumor necrosis factor after development of diabetes in non-treated, long-term diabetic BB rats.  Clin Immunol Immunopathol. 1992;  62 258-263
    CrossrefPubMedGoogle Scholar
  • 15 Taniguchi A, Nakai Y, Doi K, Fukuzawa H, Fukushima M, Kawamura H, Tokuyama K, Suzuki M, Fujitani J, Tanaka H, Nagata I. Insulin sensitivity, insulin secretion, and glucose effectiveness in obese subjects: a minimal model analysis.  Metabolism. 1995;  44 1397-1400
    CrossrefPubMedGoogle Scholar
  • 16 World Health Organization .Diabetes Mellitus: Report of a WHO Study Group. Geneva; World Health Org 1985 (Tech. Rep. Ser., no 727)
    Google Scholar
  • 17 Friedewald W T, Levy R I, Fredrickson D S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.  Clin Chem. 1972;  18 499-502
    CrossrefPubMedGoogle Scholar
  • 18 Nakai Y, Hamagaki S, Seino Y, Takagi R, Taniguchi A, Kurimoto F. Plasma concentrations of tumor necrosis factor-α (TNF-α) and soluble TNF receptors in patients with anorexia nervosa.  J Clin Endocrinol Metab. 1999;  84 1226-1228
    CrossrefPubMedGoogle Scholar
  • 19 Gatling W, Knight C, Hill R D. Screening for early diabetic nephropathy: which sample to detect microalbuminuria?.  Diabetic Med. 1985;  2 451-455
    PubMedGoogle Scholar
  • 20 Cowell C T, Rodgers S, Silkink M. First morning urinary albumin concentration is a good predictor of 24-hour urinary albumin excretion in children with type 1 (insulin-dependent) diabetes.  Diabetologia. 1986;  29 97-99
    CrossrefPubMedGoogle Scholar
  • 21 Hutchison A S, O’Reilly D SJ, McCuish A C. Albumin excretion rate, albumin concentration, and albumin/creatinine ratio compared for screening diabetics for slight albuminuria.  Clin Chem. 1988;  34 2019-2021
    PubMedGoogle Scholar
  • 22 American Diabetes Associations . Nephropathy in diabetes.  Diabetes Care. 2004;  27 579-583
    PubMedGoogle Scholar
  • 23 Groop L, Ekstrand A, Forsblom C, Widen E, Groop P H, Teppo A M, Eriksson J. Insulin resistance, hypertension, and microalbuminuria in patients with type 2 (non-insulin-dependent) diabetes mellitus.  Diabetologia. 1993;  36 642-647
    CrossrefPubMedGoogle Scholar
  • 24 Gabazza E C, Takeya H, Debuchi H, Sumida Y, Taguchi O, Murata K, Nakatani K, Yano Y, Mohri M, Sata M, Shima T, Nishioka J, Suzuki K. Protein C activation in NIDDM patients.  Diabetologia. 1996;  39 1455-1461
    CrossrefPubMedGoogle Scholar
  • 25 Nielsen S, Schmitz A, Bacher T, Rehling M, Ingerslev J, Mogensen C E. Transcapillary escape rate and albuminuria in type II diabetes: Effects of short-term treatment with low-molecular weight heparin.  Diabetologia. 1999;  42 60-67
    CrossrefPubMedGoogle Scholar
  • 26 Chen J W, Gall M A, Yokoyama H, Jensen J S, Deckert M, Parving H H. Raised serum sialic acid concentration in NIDDM patients with and without diabetic nephropathy.  Diabetes Care. 1996;  19 130-134
    PubMedGoogle Scholar
  • 27 Baud L, Ardaillou R. Tumor necrosis factor alpha in glomerular injury.  Kidney Int. 1994;  45 (Suppl 45) S32-S36
    PubMedGoogle Scholar
  • 28 Klein N J, Shennan G I, Heyderman R S, Levin M. Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin, and neutrophils.  J Cell Sci. 1992;  102 821-832
    PubMedGoogle Scholar
  • 29 Nakamura T, Fukui M, Ebihara I, Osada S, Nagaoka I, Tomino Y, Koide H. mRNA expression of growth factors in glomeruli from diabetic rats.  Diabetes. 1993;  42 450-456
    PubMedGoogle Scholar
  • 30 Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, Fu C, Kislinger T, Stern D M, Schmidt A M, De Caterina R. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE. A mechanism for amplification of inflammatory responses.  Circulation. 2002;  105 816-822
    CrossrefPubMedGoogle Scholar
  • 31 Ruits-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J. Proinflammatory actions of angiotensins.  Curr Opin Nephrol Hypertens. 2001;  10 321-329
    CrossrefPubMedGoogle Scholar
  • 32 Hotamisligil G S, Arner P, Atkinson R L, Spiegelman M. Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance.  Diabetes. 1997;  46 451-455
    PubMedGoogle Scholar
  • 33 Fernandez-Real J M, Broch M, Ricart W, Casmitjana R, Gutierrez C, Vendrell J, Richart C. Plasma levels of the soluble fraction of tumor necrosis factor 2 and insulin resistance.  Diabetes. 1998;  47 1757-1762
    PubMedGoogle Scholar
  • 34 Liu L S, Spelleken M, Rohrig K, Hauner H, Eckel J. Tumor necrosis factor-α acutely inhibits insulin signaling in human adipocytes. Implication of the p80 tumor necrosis factor receptor.  Diabetes. 1998;  47 515-522
    CrossrefPubMedGoogle Scholar
  • 35 Vandenabeele P, Declercq W, Beyaert R, Fiers W. Two tumor necrosis factor receptors: structure and function.  Trends in Cell Bilogy. 1995;  5 392-399
    PubMedGoogle Scholar
  • 36 Pichler R, Maschek W, Hatzl-Griesenhofer M, Huber H, Crespillo-Gomez C, Berg J. Soluble tumor necrosis factor-α receptor 1 and interleukin-6 as markers of activity in thyrotoxic Graves’ disease.  Horm Metab Res. 2003;  35 427-433
    Article in Thieme ConnectPubMedGoogle Scholar

Ataru Taniguchi, M. D.

Division of Diabetes and Clinical Nutrition

Kansai-Denryoku Hospital · 2-1-7 Fukushima · Fukushima-ku · Osaka-city · Osaka 553-0003 · Japan

Fax: +81 (6) 64 58-69 94 ·

Email: K-58403@kepco.co.jp

      >