Tumor necrosis factor- α, adiponectin and their ratio in gestational diabetes mellitus

Caspian J Intern Med 2018; 9(1):71-77 DOI:10.22088/cjim.9.1.71 Original Article Tumor necrosis factor- α, adiponectin and their ratio in gestational diabetes mellitus Ali Khosrowbeygi (PhD) 1* Mohammad Reza Rezvanfar (MD) 2 Hassan Ahmadvand (PhD) 3 1. Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran. 2. Department of Internal Medicine, Arak University of Medical Sciences, Arak, Iran. 3. Department of Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran. * Correspondence: Ali Khosrowbeygi, Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran. Abstract Background: It has been suggested that inflammation might be implicated in the gestational diabetes mellitus (GDM) complications, including insulin resistance. The aims of the current study were to explore maternal circulating values of TNF-α, adiponectin and the adiponectin/TNF-α ratio in women with GDM compared with normal pregnancy and their relationships with metabolic syndrome biomarkers. Methods: Forty women with GDM and 40 normal pregnant women were included in the study. Commercially available enzyme-linked immunosorbent assay methods were used to measure serum levels of TNF-α and total adiponectin. Results: Women with GDM had higher values of TNF-α (225.08±27.35 vs 115.68±12.64 pg/ml, p<0.001) and lower values of adiponectin (4.50±0.38 vs 6.37±0.59 µg/ml, p=0.003) and the adiponectin/TNF-α ratio (4.31±0.05 vs 4.80±0.07, P<0.001) than normal pregnant women. The adiponectin/TNF-α ratio showed negative correlations with insulin resistance (r=-0.68, p<0.001) and triglyceride (r=-0.39, p=0.014) and a positive correlation with insulin sensitivity (r=0.69, p<0.001). Multiple linear regression analysis showed that values of the adiponectin /TNF-α ratio were independently associated with insulin resistance. Binary logistic regression analysis showed that GDM was negatively associated with adiponectin /TNF-α ratio. Conclusions: In summary, the adiponectin/TNF-α ratio decreased significantly in GDM compared with normal pregnancy. The ratio might be an informative biomarker for assessment of pregnant women at high risk of insulin resistance and dyslipidemia and for diagnosis and therapeutic monitoring aims in GDM. Keywords: Gestational diabetes mellitus, Adiponectin, Tumor necrosis factor- α, Insulin resistance Citation: Khosrowbeygi A, Rezvanfar MR, Ahmadvand H. Tumor necrosis factor- α, adiponectin and their ratio in gestational diabetes mellitus. Caspian J Intern Med 2018; 9(1):71-77. E-mail: Tel: 0098 8634173501 Fax: 0098 8634173529 Received: 3 April 2017 Revised: 17 June 2017 Accepted: 18 June 2017 estational diabetes mellitus (GDM), which is defined as glucose intolerance with G onset or first diagnosis during pregnancy, is one of the most important pregnancy complications (1-4). It affects approximately 1 to 20% of all pregnancies worldwide and its prevalence in Iranian women is about 4 to 9% of all pregnancies (5). It has been suggested that inflammation might be implicated in the GDM pathogenesis (6). In recent years, the role of pro-inflammatory cytokines such as tumor necrosis factor- α (TNF-α), and anti-inflammatory cytokine such as adiponectin has been increasingly studied in GDM (4). TNF-α is one of proposed molecules that can cause insulin resistance during pregnancy. On the other hand, adiponectin has been suggested as the strongest antiinflammatory cytokine that promotes insulin sensitization by stimulating AMP-activated protein kinase that leads to increase glucose uptake in skeletal muscle (7, 8). There are some conflicting findings of maternal circulating levels of the cytokines in women with GDM compared with normal pregnancy (5, 7). Caspian J Intern Med 2018; 9(1):71-77 Khosrowbeygi A, et al. 72 Therefore, the aims of the current study were to explore maternal circulating values of TNF-α, adiponectin and the adiponectin/TNF-α ratio in Iranian women with GDM compared with normal pregnancy and their relationships with metabolic syndrome biomarkers. Methods This case-control study was conducted at the Obstetrics and Gynecology Hospital of Lorestan University of Medical Sciences (July, 2014- March, 2015) after being approved by the Institutional Ethics Review Board. Informed consent was obtained from each pregnant woman enrolled in this study. The study population consisted of 40 nulliparous women with newly diagnosed GDM before any drug treatment, and 40 normal nulliparous pregnant women at 24-28 weeks of gestation. All subjects were Iranian with Lor ethnicity. The diagnosis of GDM was made according to the 75-g oral glucose tolerance test (OGTT) (9). Exclusion criteria were smoking, multiparity, diabetes mellitus, chronic hypertension, preeclampsia and the patients who were under treatment with metformin or insulin (10). Commercially available photometric methods were used to measure fasting serum levels of glucose (FBG), total cholesterol (TC), triglyceride (TG) (ZiestChem Diagnostic, Tehran, Iran) and high-density lipoprotein cholesterol (HDLC) (Parsazmun, Karaj, Iran) using a chemistry analyzer (Hitachi, Germany). The intra-assay and inter-assay coefficients of variation were <10% according to the manufacturers. Low-density lipoprotein cholesterol (LDL-C) was estimated by Friedewald’s equation (11). The lipid ratios including the TC/HDL-C ratio, the LDL-C/HDL-C ratio and the TG/TC ratio were calculated (12). The atherogenic index of plasma (AIP) was calculated using log (TG/HDL-C) formula (13). Commercially available enzyme-linked immunosorbent assay (ELISA) methods were used to measure serum levels of TNF-α (Ani Biotech Oy, Orgenium Laboratories Business Unit, Finland), total adiponectin (BioVendor Laboratory Medicine, Inc. Czech Republic) and insulin (Monobind Inc., USA) using an ELISA reader (STAT FAX 3200, USA). The intra-assay coefficient of variation of all the ELISA assays was <10% according to the manufacture. The sensitivities of the assays were 15 pg/ml, 26 ng/ml and 0.75µIU/ml, respectively, according to the manufacture. The adiponectin/TNF-α ratio was calculated and log-transformed. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR) index formula (14). The quantitative insulin sensitivity check index (QUICKI) was used to estimate insulin sensitivity (15). The Kolmogorov–Smirnov test was used to explore the normality of distribution of the variables. The Student t-test and Pearson’s correlation analysis were used to do statistical calculations for quantitative variables with normal distributions. Skewed parameters were analyzed by the Mann–Whitney U-test and Spearman’s correlation. Multiple linear regression analysis was also performed to determine the independent predictors of FBG, the HOMA-IR index and the QUICKI as the dependent variables. Non-normally distributed par (...truncated)