Winkler Gábor, Cseh Károly, Baranyi Eva, Melczer Zsolt, Speer Gábor, Hajós Péter, Salamon Ferenc, Turi Zsuzsa, Kovács Margit, Vargha Péter, Karádi István
Second Department of Internal Medicine, St. John's Hospital, H-1125, Diós Arok 1, Budapest, Hungary.
Diabetes Res Clin Pract. 2002 May;56(2):93-9. doi: 10.1016/s0168-8227(01)00355-2.
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.
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.
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).
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.
本研究旨在探讨肿瘤坏死因子（TNF）系统在妊娠期糖尿病（GDM）患者及正常妊娠过程中胰岛素抵抗的病理生理作用。
研究了30例患有GDM的女性（孕16 - 39周）、35例健康孕妇（15例孕早期、9例孕中期和11例孕晚期）以及25例年龄匹配的健康非孕女性。检测血清TNF-α及其可溶性受体1和2（sTNFR-1和-2）。
在孕晚期的非糖尿病孕妇中，所有检测指标均显著高于孕早期和非孕女性（BMI分别为27.6±4.1（±标准差）、24.1±2.6、22.4±2.4kg/m²），血清TNF-α（分别为4.6±0.6、4.1±0.4、4.1±0.4ng/l），sTNFR-1（分别为2.7±0.9、2.0±0.5、2.0±0.1μg/l），sTNFR-2（分别为5.6±2.6、4.6±2.1、3.3±0.2μg/l），C肽（分别为3.1±1.7、1.1±0.7、1.1±0.8μg/l），以及C肽与血糖比值（分别为0.6±0.2、0.2±0.1、0.2±0.1μg/mmol）。在GDM患者中，这些指标甚至高于健康孕妇的任何亚组（BMI）（33.4±6.4kg/m²，TNF-α）（6.3±0.6μg/l），sTNFR-1（3.0±0.5μg/l），sTNFR-2（10.0±6.9μg/l，C肽6.0±2.7μg/l，C肽与血糖比值：1.2±0.5μg/mmol，P<0.01）。在妊娠期糖尿病和非糖尿病女性中，血清TNF-α、C肽水平与BMI之间存在显著（P<0.01）的正线性相关性。在妊娠期糖尿病女性中，在多变量分析中研究C肽的依赖性时，仅BMI仍具有显著性（r² = 0.67，P = 0.01）。
我们的观察强调了在正常妊娠和GDM过程中，由脂肪细胞因子如TNF-α及其受体驱动的与肥胖相关的胰岛素抵抗成分。
