The fasting and post load glucose, HbA1c, fasting insulin, and HOMA-IR levels were statistically significantly higher in the GDM group. Because GDM occurs as a result of the progressive advancement of insulin resistance, blood glucose, and insulin levels were expected to be higher than those of the healthy group. Significant increases in fasting insulin levels and HOMA-IR were determined. Metabolic parameters of women with GDM that were comparable to those observed in obesity and type 2 DM 20
Lipid profiles of the two groups were not significantly different except triglyceride levels. In pregnancy, total cholesterol and triglyceride levels are expected to increase, but the ranges are variable according to various studies performed 21-23. High levels of triglyceride and low levels of HDL-cholesterol are typical findings of metabolic syndrome and diabetes mellitus. Insulin resistance and GDM, may lead to the development of higher triglyceride levels in the GDM group.
In our study, the hs-CRP level in the GDM group was significantly higher than that of the healthy group. The hs-CRP is accepted as a risk factor for atherosclerosis, myocardial infarction and stroke 24. C-reactive protein secreted from liver has an important role in immune response. The hs-CRP activates many inflammatory processes. In human endothelial cells, hs-CRP stimulates adhesion proteins like vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and monocyte chemo-attractant protein-1 (MCP-1) 5. Also in human monocytes hs-CRP stimulates the production of tissue factor that has a role in extrinsic coagulation pathway 24. Retnakaran et al. 8 reported that the obesity is the factor that influences the CRP levels in GDM patients. In another report, the patients who previously had GDM also had higher levels of CRP 25. Even after GDM, chronic inflammation and thus the CAD risk probably continue. Bo et al. 26 reported that post-GDM women had higher levels of E-selectin, intracellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), hs-CRP and IMT (intima media thickness) than the controls. Thus, these studies have led to the conclusion that GDM patients will have an increased risk of cardiovascular disease in the future 26.
OPN is a glycoprotein and acts as a multifunctional pro-inflammatory cytokine. It is secreted from activated T cells, NK cells, dendritic cells and monocytes/macrophages. OPN plays an important role in the physiologic and pathologic events including angiogenesis, apoptosis, inflammation, wound healing and tumor metastasis 27,28. OPN levels increase in chronic inflammation, and it may have a function in the pathogenesis of atherosclerosis 29. Nakamachi et al. 30 reported that PPRα agonists suppress OPN expression in macrophage cell cultures and decrease OPN levels in type 2 diabetic patients. In conclusion, all these information suggest the possible role of OPN in macrophage-derived inflammatory process. In another paper, the authors reported that in pre-eclamptic patients OPN concentrations increased in association with extensive endothelial injury 14. Yan et al. 31 reported higher OPN levels in type 2 diabetic patients and demonstrated the existence of an independent association with the presence and severity of nephropathy and CAD. In another article, Ahmad et al. 13 reported that IL-8 plays a significant role in the secretion of plasma OPN levels. They also noticed that IL-8 and OPN levels increased in correlation with insulin resistance in obese patients 13. In a large-scale study conducted in young adults, OPN was shown not to be of interest regarding vascular markers of subclinical atherosclerosis 12. In another study, OPN was suggested to be the first indicator of coronary artery calcification in asymptomatic CAD in patients with type 2 DM 32. Despite contradictory publications, in an article involvement of OPN in insulin resistance, obesity, chronic inflammation, such as CAD has been demonstrated 33. As indicated in this paper, in spite of favourable changes in insulin resistance, levels of OPN increased in bariatric surgery 33. In this study, increased OPN levels were correlated with the increased osteocalcin and C-telopeptide levels 33. The association of OPN with insulin/glucose levels and atherosclerosis has been reported in an experimental study 34. As demonstrated in that study, an increase in blood glucose levels activates NFAT (Nuclear Factor of Activated T-cell) which leads to an increase in OPN mRNA 34. A similar study was done previously by Winhofer et al 16. In that study, lower OPN levels were detected in patients with GDM compared with the control group, and any correlation could not be found between OPN and insulin levels/secretion 16. The authors also reported that OPN levels had increased during postpartum period 16. The authors concluded that OPN might have local importance and it is not an underlying factor in the development of insulin resistance in GDM patients. Correlation between OPN, and CRP/hs-CRP levels was also reported. In our study we reported that OPN levels were not different in GDM group than the healthy group and there was no correlation with the hs-CRP levels. We did not study the postpartum OPN levels, so we do not know any postpartum effect on OPN levels. The important role of OPN in vascular calcification has been shown in insulin resistance, obesity, and chronic inflammation in atherosclerosis. In GDM or bariatric surgery, patients are experiencing rapid metabolic changes. So these metabolic changes may not affect the level of OPN. However, in chronic diseases such as type 2 Diabetes or CAD, blood OPN levels may be correlated with the disease duration.
The limitations of our study were as follows: More significant results could be obtained if greater number of patients could be investigated in a longer study period. And also if a group of diabetic patients who were not pregnant could be enrolled in the study; then more meaningful results could be reported. If the weight gain during pregnancy had been considered, there might have been statistically significant correlation with the OPN. We could have obtained highly significant results, if we could evaluate OPN levels during postpartum period.