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
- 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
- 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
- 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
- 5
Mogensen C E.
Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset
diabetes.
N Engl J Med.
1984;
310
356-360
- 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
- 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
- 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
- 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
- 10
Tartaglia L A, Goeddel D V.
Two TNF receptors.
Immunol Today.
1992;
13
151-153
- 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
- 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
- 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
- 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
- 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
- 16 World Health Organization .Diabetes Mellitus: Report of a WHO Study Group. Geneva;
World Health Org 1985 (Tech. Rep. Ser., no 727)
- 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
- 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
- 19
Gatling W, Knight C, Hill R D.
Screening for early diabetic nephropathy: which sample to detect microalbuminuria?.
Diabetic Med.
1985;
2
451-455
- 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
- 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
- 22
American Diabetes Associations .
Nephropathy in diabetes.
Diabetes Care.
2004;
27
579-583
- 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
- 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
- 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
- 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
- 27
Baud L, Ardaillou R.
Tumor necrosis factor alpha in glomerular injury.
Kidney Int.
1994;
45 (Suppl 45)
S32-S36
- 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
- 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
- 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
- 31
Ruits-Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J.
Proinflammatory actions of angiotensins.
Curr Opin Nephrol Hypertens.
2001;
10
321-329
- 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
- 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
- 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
- 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
- 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
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