Serum Vaspin, Leptin And Adiponectin Levels In Gestational Diabetes Mellitus And The Relationship Of Them To Insulin Resistance

Objective: Along with the rapid development of social economy, the improvement of people’s living standards and the formation of an unhealthy lifestyle, there was increasing health problems for people. The morbidity and the number of patients of diabetes and gestational diabetes mellitus(GDM) has been increased dramatically, and our country was a major disaster area of diabetes. GDM is a special type of diabetes, it will increase the risk of adverse pregnancy outcome and the mortality in perinatal period, and cause the occurring of the mother’s late onset of type 2 diabetes mellitus(T2DM), fetal malformation and macrosomia, neonatal hypoglycemia and so on. Researchers reported that gestational weeks, obesity, environmental factors, race, eating habits, abnormal childbearing history, family history of diabetes, economic and cultural level are all playing an important role in the occurrence of GDM. GDM is related with the relatively insufficient of insulin secretion and insulin resistance(IR), IR is an important characteristic of GDM. IR is mainly manifested in the reduced effect of insulin on body cells, such as fat, muscle and liver. So far, the mechanism of IR is unclear, to our knowledge, exercise and weight loss could improve insulin sensitivity, studies also suggested that adipocytokines play a role in insulin sensitivity. In this study, we detected the vaspin, leptin and adiponectin levels, the aim was to explore their variation in pregnant women with and without GDM and healthy non-pregnant women, and to analyze the relationship between adipocytokines and IR.Methods: In this case-control study, from July 2012 to April 2013, we enrolled newly diagnosed GDM women(n=86), pregnant women without GDM((n=92)) and healthy non-pregnant women(84),who presented to the First Hospital of Qinhuangdao for obstetrical examination or healthexamination. In addition, younger than 18 years old or older than 40 years old[1], multipara, diabetes, liver or renal insufficiency, rheumatologic disease, thyroid diseases, polycystic ovary syndrome(PCOS), tumor, use of corticosteroids or metformin, and acute or chronic inflammation were excluded. Subjects are all collected the following information, age, gestational weeks, weight at pre-pregnancy in pregnancy(weight-1), family history of diabetes were recorded, height, weight, blood pressure were measured, and hemoglobin A1c(Hb A1c), fasting blood glucose(FBG), glucose(1h、2h), fasting insulin(FINS), triglycerides(TG), high-density lipoprotein cholesterol(HDL-c) were detected, vaspin, leptin and adiponectin were determined by enzyme-linked immunosorbent assay(ELISA). To calculate the body mass index(BMI)(including BMI-1 and BMI-2), weight gain and h o m e o s t a s i s m o d e l a s s e s s m e n t- i n s u l i n r e s i s t a n c e( H O M A- I R). All analyses were performed using the SPSS 13.0 statistical software(SPSS Company, Chicago, Illinois, USA). Measurement data were expressed as mean±standard deviation, and enumeration data were expressed rate, using t test, ANOVA or Chi square for comparisons, as appropriate. To measure the strength of the association between two variables, a simple scatter plot and Spearman correlation coefficient were used. Three multiple linear regression models(stepwise method) were used to evaluate the relationships between vaspin, leptin, adiponectin and other variables with HOMA-IR. HOMA–IR as the dependent variable, and age, BMI-1, BMI-2, gestational weeks, weight gain, vaspin, leptin, adiponectin, TG, and HDL-c were used as independent variables in the GDM group(model 1) and normal pregnancy(model 2). Age, BMI-2, vaspin, leptin, adiponectin, TG, and HDL-c were used as independent variables in the healthy non-pregnant group(model 3). Furthermore, normal pregnancy was rated as 0 and GDM group as 1 within dependent variable, age, BMI-1, BMI-2, weight gain, vaspin, leptin, adiponectin, HOMA-IR, TG and HDL-c as independents, a binary logistic regression analysis(enter method) was performed. P<0.05 was considered statistically significant.Results:1 Clinical and laboratory characteristics in the study subjects are shown that age, diastolic blood pressure(DBP), height, family history of diabetes, weight-1 and BMI-1 were similar among the three groups(P>0.05). Though BMI-2 in pregnancy with and without GDM were similar(P>0.05), but BMI-2 in pregnant was significant higher than in non-pregnant group(P<0.05). Furthermore, weight gain and gestational weeks were higher in normal pregnancy than in GDM(P<0.05). 2 Hb A1 c and HOMA-IR were different among the three groups(P<0.05). FINS levels was higher in GDM and normal pregnancy than in non-pregnant women(P<0.05), however, there was only a rising trend in GDM(P>0.05). Moreover, HDL-c levels were significantly different in three groups, and it is more lower in GDM than in normal pregnancy(P<0.05), there is different levels of TG between pregnancy and non-pregnancy, but not in GDM and normal pregnancy. 3 Data inferred higher concentrations of vaspin(2.72 ± 2.20 vs. 1.84 ± 1.57 vs. 0.81 ± 1.02), higher leptin(23.42 ± 12.18 vs. 22.19 ± 10.55 vs. 12.10 ± 11.26), and lower adiponectin(4164.83 ± 2650.39 vs. 4871.66 ± 2803.51 vs. 7202.85 ± 4893.13) in GDM than during normal pregnancy and in non-pregnant women(P<0.05). 4 Correlation analysis for vaspin, leptin, adiponectin, HOMA-IR and other parameters 4.1 In GDM group, Vaspin was positively correlated to HOMA–IR(r=0.387, P<0.001), FINS and TG, leptin was positively correlated to HOMA-IR(r=0.419, P<0.001), FINS, BMI-2, and it was negatively correlated to age. Adiponectin was negatively correlated to HOMA-IR(r=-0.182, P=0.018), FINS, BMI-1 and BMI-2. Furthermore, Vaspin was positively correlated to leptin(r=0.273, P=0.012), and leptin was negatively correlated to adiponectin(r=-0.336, P=0.002). HOMA-IR was positively correlated to BMI-1, BMI-2 and TG. 4.2 In normal pregnancy, leptin was positively correlated to HOMA-IR(r=0.213, P=0.041) and BMI-1, BMI-2. Adiponectin was negatively correlated to HOMA-IR(r=-0.286, P=0.006), FINS, BMI-1 and BMI-2. There was no correlation between vaspin and other variables. In addition, leptin was negatively correlated to adiponectin(r=-0.256, P=0.014). HOMA-IR was positively correlated to BMI-1 and TG. 4.3 In non-pregnant group, leptin was positively correlated to HOMA-IR(r=0.504, P<0.001), FINS, and BMI-2.Adiponectin was negatively correlated to HOMA-IR(r=-0.240, P=0.032), FINS, BMI-2 and TG, and positively correlated to HDL-c. There was also no correlation between vaspin and other variables. Moreover, HOMA-IR was positively correlated to BMI-2 and TG, and was negatively correlated to age. 5 Results of multiple linear regression analysis and binary logistic regression analysis 5.1 In GDM group, HOMA-IR was independently associated with BMI-2, vaspin, and leptin(R2=0.419). In normal pregnancy group, HOMA–IR was independently associated with adiponectin and TG, the regression equation was ?=1.8-0.00008(adiponectin)+0.187(TG), R=0.356, R2=0.127. And in non-pregnant women group, HOMA–IR was only independently associated with BMI-2, the regression equation was ?=-1.694+0.148(BMI-2), R=0.590, R2=0.384。 5.2 In binary logistic regression, vaspin, HOMA-IR,HDL-c and weight gain were independently associated with GDM.Conclusions:1 There were different IR among the three groups, the GDM group was the most serious, the normal pregnant group occupied second place, and the healthy non-pregnant women comes third. 2 Data inferred higher concentrations of vaspin, higher leptin, and lower adiponectin in GDM than during normal pregnancy and in non-pregnant women, the vaspin levels were different among the three groups, but no significant difference between GDM and normal pregnancy individules for leptin and adiponectin. 3 There are correlations between vaspin, leptin, adiponectin and IR, and levels of vaspin and leptin might be associated with IR in GDM, but it is still not sure about the adiponectin.