Abstract
Plasma concentrations of adiponectin, tumor necrosis factor-α (TNF-α) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 ± 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 ± 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 ± 5.91 vs. 16.31 ± 6.04 μg/ml, p = 0.00009) and elevated levels of TNF-α (1.71 ± 0.92 vs. 1.27 ± 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-α concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-α correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-α concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62 % of the variance in TNF-α concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39 % of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.
Key words
Gestational diabetes mellitus - Tumor necrosis factor-α - sTNFR-1 - sTNFR-2 - Adiponectin
References
-
1
Zuopas C.
Gestational diabetes mellitus.
Diabetes Rev Int.
1995;
4
5-7
-
2
Catalano P M, Tyzbir E D, Roman N M, Amini S B, Sims E AH.
Longitudinal changes in insulin release and insulin resistance in non-obese pregnant women.
Am J Obstet Gynecol.
1991;
165
1667-1672
-
3
Buchanan T A, Metzger B E, Freinkel N, Berman R N.
Insulin sensitivity and beta-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes.
Am J Obstet Gynecol.
1990;
162
1008-1014
-
4
Gilbert M, Basile S, Buadelin A, Pere M C.
Lowering plasma free fatty acid levels improves insulin action in conscious pregnant rabbits.
Am J Physiol.
1993;
264
E576-E582
-
5
Stehbens W E.
The epidemiological relationship of hypercholesterolemia, hypertension, diabetes mellitus and obesity to coronary heart disease and atherogenesis.
J Clin Epidemiol.
1990;
43
733-741
-
6
Pi-Sunyer F X.
Comorbidities of overweight and obesity: current evidence and research issues.
Med Sci Sports Exerc.
1999;
31
S602-S608
-
7
Hotamisligil G S, Spigelman B M.
Tumor necrosis factor alpha - a key component of the obesity-diabetes link.
Diabetes.
1994;
43
1271-1278
-
8
Hotamisligil G S, Murray D L, Choy L N, Spiegelman B M.
Tumor necrosis factor-α inhibits signaling from the insulin receptor.
Proc Natl Acad Sci USA.
1994;
91
4854-4858
-
9
Stephens J N, Lee J, Pilch P F.
Tumor necrosis factor-α induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction.
J Biol Chem.
1997;
272
971-976
-
10
Daher S, Fonseca F, Ribeioro O G, Musatti C C, Gerbase-DeLima M.
Tumor necrosis factor during pregnancy and at the onset of labour and spontaneous abortion.
Eur J Obstet Gynecol Reprod Biol.
1999;
83
77-79
-
11
Argiles J M, Carbo N, Lopes-Soriano F J.
TNF and pregnancy: the paradigm of a complex interaction.
Cytokine Growth Factor Rev.
1997;
8
181-188
-
12
Kirwan J P, Hauguel-de Mouzon S, Lepercq J, Challier J C, Huston-Presley L, Friedman J F, Kalhan S C, Catalano P M.
TNF-α is a predictor of insulin resistance in human pregnancy.
Diabetes.
2002;
51
2207-2213
-
13
Coughlan M T, Oliva K, Georgiou H M, Parmezel J MH, Rice G E.
Glucose-induced release of tumor necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus.
Diabet Med.
2001;
18
921-927
-
14
Hotamisligil G S, Arner P, Atkinson R L, Spiegelman B M.
Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance.
Diabetes.
1987;
46
451-455
-
15
Fernandez-Real J M, Broch M, Ricart W, Casamitjana R, Gutierrez C, Vendrell J, Richart C.
Plasma levels of the soluble fraction of tumor necrosis factor receptor 2 and insulin resistance.
Diabetes.
1998;
47
1757-1762
-
16
Scherer P E, Williams S, Fogliano M, Baldini G, Lodish H F.
A novel serum protein similar to C1q produced extensively in adipocytes.
J Biol Chem.
1995;
270
26 746-26 749
-
17
Hu E, Liang P, Spiegelman B M.
AdipoQ is a novel adipose-specific gene dysregulated in obesity.
J Biol Chem.
1996;
271
10 697-10 703
-
18
Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay R S, Youngren J F, Havel P J, Pratley R E, Bogardas C, Tataranni P A.
Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.
Diabetes.
2002;
50
1884-1888
-
19
Ukkola O, Santaniemi M.
Adiponectin: a link between excess adiposity and associated comorbidities?.
J Mol Med.
2002;
80
696-702
-
20
Arita Y, Kihara S, Oguchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Schimomura I, Nakamura T, Miyoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y.
Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem.
Biophys Res Commun.
1996;
257
79-83
-
21
Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A.
Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
J Clin Endocrinol Metab.
2001;
86
1930-1935
-
22
Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Schimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y.
Association of hypoadiponectinemia and coronary artery disease in men.
Arterioscler Thromb Vasc Biol.
2003;
23
85-89
-
23
Iwahashi H, Funahashi T, Kurokawa , Sayama K, Fukuda E, Okita K, Imagawa A, Yamagata K, Shimomura I, Miyagawa J-I, Matsuzawa Y.
Plasma adiponectin levels in women with anorexia nervosa.
Horm Metab Res.
2003;
35
537-540
-
24
Brichard S M, Delporte M I, Lambert M.
Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin.
Horm Metab Res.
2003;
35
337-342
-
25
Maeda N, Shimomura I, Kishida K.
Diet-induced insulin resistance in mice lacking adiponectin/Acrp30.
Nat Med.
2002;
8
731-737
-
26
Hotamisligl G S, Arner P, Caro J F, Atkinson R L, Spiegelman B M.
Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance.
J Clin Invest.
1995;
95
2409-2415
-
27
Friedewald W T, Levy R I, Fredrickson P S.
Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of the preparative ultracentrifuge.
Clin Chem.
1972;
18
499-506
-
28
Winkler G, Cseh K, Baranyi E, Melczer Z, Speer G, Hajos P, Salamon F, Turi Z, Kovacs M, Vargha P, Karadi I.
Tumor necrosis factor system in insulin resistance in gestational diabetes.
Diabetes Res Clin Pract.
2002;
56
93-99
-
29
Melczer Z S, Banhidy F, Csomor S Jr, Kovasc M, Siklos P, Winkler G, Cseh K.
Role of tumor necrosis factor-α in insulin resistance during normal pregnancy.
Eur J Obstet Gynecol and Reprod Biol.
2002;
105
7-10
-
30
Cseh K, Baranyi E, Melczer Z, Csakany G M, Speer G, Kovacs M, Gero˝ G, Karadi I, Winkler G.
The pathophysiological influence of leptin and the tumor necrosis factor system on maternal insulin resistance: negative correlation with anthropometric parameters of neonates in gestational diabetes.
Gynecol Endocrinol.
2002;
16
453-460
-
31
Hotamisligil G S.
Mechanisms of TNF-α induced insulin resistance.
Exp Clin Endocrinol Diabetes.
1999;
107
119-125
-
32
Cseh K, Winkler G, Melczer Z.
The role of tumor necrosis factor (TNF)-α resistance in obesity and insulin resistance.
Diabetologia.
2000;
43
525
-
33
Hulthe J, Hulten L M, Fagerberg B.
Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles: atherosclerosis and insulin resistance study.
Metabolism.
2003;
52
1612-1614
-
34
Cseh K, Baranyi E, Melczer Z, Kaszas E, Palik E, Winkler G.
Plasma adiponectin and pregnancy-induced insulin resistance.
Diabetes Care.
2004;
27
274-275
-
35
Retnakaran R, Hanley A JG, Raif N, Connely P W, Sermer M, Zinman B.
Reduced adiponectin concentration in women with gestational diabetes.
Diabetes Care.
2004;
27
799-800
-
36
Ranheim T, Haugen F, Staff A C, Braekke K, Harsem N K, Drevon C A.
Adiponectin is reduced in gestational diabetes mellitus in normal weight women.
Acta Obstet Gynecol Scand.
2004;
83
341-347
-
37
Williams M A, Qiu C, Muy-Rivera M, Vadachkoria S, Song T, Luthy D A.
Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetes mellitus.
J Clin Endocrinol Metab.
2004;
89
2306-2311
-
38
Lindsay R S, Funahashi T, Hanson R L, Matsuzawa Y, Tanaka S, Tataranni P A, Knowler W C, Krakoff J.
Adiponectin and development of type 2 diabetes in the Pima Indians population.
Lancet.
2002;
360
57-58
-
39
Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Kato T.
Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population.
Diabetes Care.
2003;
26
2015-2020
M. Kinalski
Department of Pathophysiology of Pregnancy, Medical University of Białystok
ul. M. Curie-Skłodowska 24A · 15-276 Białystok · Poland
Telefon: +48(85)7468352
Fax: +48(85)7468682 ·
eMail: Telejkob@poczta.onet.pl
