Tumor necrosis factor system in insulin resistance in gestational diabetes.
OBJECTIVE
The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy.


METHODS
Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured.


RESULTS
In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01).


CONCLUSIONS
Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.
Winkler
Gábor
G
Second Department of Internal Medicine, St. John's Hospital, H-1125, Diós Arok 1, Budapest, Hungary. winkler.gabor@axelero.hu
Cseh
Károly
K
Baranyi
Eva
E
Melczer
Zsolt
Z
Speer
Gábor
G
Hajós
Péter
P
Salamon
Ferenc
F
Turi
Zsuzsa
Z
Kovács
Margit
M
Vargha
Péter
P
Karádi
István
I
D015703:Antigens, CD / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016640:Diabetes, Gestational / Q000097:blood / Q000503:physiopathology*; D005260:Female; D019270:Fructosamine / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis; D006304:Health Status; D006801:Humans; D007333:Insulin Resistance; D011247:Pregnancy; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015703:Antigens, CD; D001786:Blood Glucose; D002096:C-Peptide; D019270:Fructosamine; D006442:Glycated Hemoglobin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha