Association Of Serum α2-HS-Glycoprotein Concentration With Insulin Resistance And Glucolipid Metabolism In Patients With Gestational Diabetes

Objective⑴To investigate the state of insulin resistance and the function of isletβ-cell in patients with gestational diabetes mellitus (GDM), healthy pregnant women and non-pregnant women with type-2 diabetes mellitus (T2DM).⑵To difine the relationship among serum AHSG levels and insulin resistance, glucolipid metabolism, and whether this protein is involved in insulin resistance observed in patients with GDM, healthy pregnant women and non-pregnant women with T2DM.Method⑴Thirty pregnant women with GDM ( GDM group ), Thirty pregnant women with normal glucose tolerance ( normal pregnancy group ) and non-pregnant women with T2DM ( group T2DM ) were selected. Blood glucose concentration was measured by glucose oxidase method, and insulin and C-peptide levels were determined by chemiluminescence method. To analyse the state of insulin resistance and the function ofβ-cell of islet with Homeostasis model assessment-insulin resistance index ( HOMA-IRI ) and islet secretive function index ( IFI ).⑵Enzyme-linked immunosorbent assay was used to measure the fasting serum AHSG levels of GDM group, normal pregnancy group in late trimester and 22 cases of non-pregnant women random selected from T2DM group ( T2DM groupⅠ). Pregnant women's fasting total cholesterol (TC), triglyceride (TG), very low-density lipoprotein cholesterol (VLDL-C), and fasting plasma glucose (FPG), insulin (FINS), C-peptide, glycosylated hemoglobin (HbA1c) were also measured at the same time. HOMA-IRI and IFI was calculated by formula.Results⑴In the mid trimester of pregnancy, the value of HOMA-IRI in women with GDM [ ( 0.9±0.4 ) ] were significantly higher than that of normal pregnant women [ ( 0.4±0.3 ) ] ( P<0.01 ), while significantly lower than that of non-pregnant women with T2DM [ ( 1.3±0.4 ) ] ( P<0.01 ). The value of IFI in women with GDM [ ( 0.7±0.4 ) ] has no significant difference as compared with normal pregnant women [ ( 0.6±0.4 ) ] ( P>0.05 ), but significantly higher than that of non-pregnant women with T2DM [ ( 0.1±0.4 ) ] ( P<0.01 ). The phase of fast insulin secretion after oral glucose is normal in normal pregnancy group, as well as the peak value of insulin and C-peptide was found at the first hour of postoral glucose in normal pregnant women, while at the second hour in GDM and T2DM group. Also the function of fast insulin secretion when glucose stimulation was found defected in GDM and T2DM group.⑵In late pregnancy, the value of HOMA-IRI in women with GDM [ ( 1.5±0.3 ) ] were significantly higher than that of normal pregnant women [ ( 0.9±0.3 ) ] ( P<0.01 ), but no significant differences was found as compared with T2DM group [ ( 1.3±0.4 ) ]. And the value of HOMA-IRI in normal pregnant women were lower than tnat of non-pregnant women with T2DM ( P<0.01 ). The value of IFI in group of GDM [ ( 1.2±0.2 ) ] and normal pregnancy [ ( 1.1±0.2 ) ] have no significant differences ( P>0.05 ), but were all significantly higher than that of T2DM group[ ( 0.1±0.4 ) ] respectively ( P<0.01 ). As well as significantly elevated HOMA-IRI and IFI levels was found in the group of GDM and normal pregnancy in late trimester of pregnancy as compared with that in the mid trimester of pregnancy respectively ( P<0.01 ).⑶Significantly elevated serum AHSG concentration was found in the women with GDM [ ( 223.8±117.0 ) ng/ml] as compared with the normal pregnant women [ ( 149.6±70.6 ) ng/ml ] and non-pregnant women with T2DM [ ( 124.7±56.3 ) ng/ml ] ( P<0.01 ). And no significant differences was found between the normal pregnancy group and T2DM groupⅠ( P>0.05 ).⑷The concentration of serum TC, TG and VLDL-C [ ( 6.3±1.1 ) mmol/L, ( 3.8±1.1 ) mmol/L, (1.8±0.7) mmol/L] in GDM group were significantly higher than those of normal pregnancy group [ ( 5.7±0.5 ) mmol/L, ( 2.8±0.7 ) mmol/L, ( 1.2±0.3 ) mmol/L] ( P<0.05 or P<0.01 ).⑸The concentration of FPG, FINS and C-peptide in GDM group were ( 5.6±0.8 ) mmol/L, ( 18.1±3.4 ) uIU/ml and ( 6.2±0.7 ) ng/ml, being significantly higher than those of the normal pregnant women [ ( 4.3±0.6 ) mmol/L, ( 13.5±2.6 ) uIU/ml, ( 5.6±1.0 ) ng/ml ] (P<0.01). The concentration of FPG, FINS and C-peptide in T2DM groupⅠwere ( 7.7±0.9 ) mmol/L, ( 12.8±2.5 ) uIU/ml, ( 5.8±0.8 ) ng/ml. The FPG levels in T2DM groupⅠwere significantly higher than that of GDM group and normal pregnancy group ( P<0.01 ), while the FINS and C-peptide levels were significantly lower than those of GDM group ( P<0.01 ). Also the C-peptide levels in in T2DM groupⅠwere significantly lower than that of normal pregnant women ( P<0.01 ), but the FINS levels has no significant difference ( P>0.05 ).⑹The concentration of HbA1c in GDM group were ( 5.8±0.9 )%, being significantly higher than that of normal pregnancy group [ ( 4.1±0.6 )%] ( P<0.01 ).⑺Univariate linear correlation and regression analysis showed serum AHSG to be positively correlated with HOMA-IR, TC, TG, VLDL-C, weight gain during pregnancy, BMI in late pregnancy, FPG, FINS, C-peptide and HbA1c ( r=0.831, 0.789, 0.620, 0.478, 0.901, 0.686, 0.844, 0.663, 0.477, 0.827, P<0.01) in GDM group, but no correlation between AHSG and progestational BMI, IFI was found ( r=–0.020,–0.009, P>0.05 ). In normal group there is also significantly positive correlations between AHSG and HOMA-IR, FPG, HbA1c ( r=0.718, 0.846, 0.538, P<0.01 ); the correlations between AHSG and FINS, C-peptide, and weight gain during pregnancy was also found ( r=0.401, 0.386, 0.370, P<0.05 ), but less significant than those in the GDM group ; there is no correlations between AHSG and TC, TG, VLDL-C, IFI, progestational BMI, BMI in late pregnancy ( r=0.164, 0.009,–0.116,–0.173, 0.144, 0.214, P>0.05 ). And there is significantly positive correlations between AHSG and HOMA-IR, FPG, FINS and C-peptide ( r=0.884, 0.731, 0.751, P<0.01) and no correlations between AHSG and IFI ( r=0.062, P>0.05 ) in T2DM groupⅠ.Conclusion⑴Women with GDM have been more insulin resistance than normal pregnant women. And in late pregnancy women with GDM have the same state in insulin resistance with T2DM patients. Also the function of isletβ-cell was defected in women with GDM, but still to remain better function reserve than T2DM patients. It is possible that there was a lengthy course of insulin resistance and then resulting in failure to insulin secretion during the development from GDM to T2DM.⑵Fasting serum AHSG levels in pregnant women with GDM is significantly higher than in normal pregnant women. A significantly positive correlation between AHSG and HOMA-IR is found in late pregnancy women and non-pregnant women with T2DM. Also the concentration of serum AHSG is positively correlated with the indiscriminate glycolipid indexes, weight gain during pregnancy in GDM. It suggests that increased AHSG may contribute to insulin resistance during normal pregnancy and GDM and T2DM. Also, AHSG is involved in the formation of glycolipid metabolic disorder in pregnant women with GDM.