Gestational diabetes mellitus is a clinical condition of impaired glucose tolerance that begins or is first determined during pregnancy. Betatrophin, a recent biomarker, has been shown to play a role in lipid and glucose metabolism [24, 25]. Studies that have aimed to determine the role of betatrophin in the pathophysiology of GDM, have mainly focused on the glucose metabolism parameters, and its effect on impaired lipid metabolism has not been shown.
In this study, LDL subfractions and biomarkers of lipid metabolism were evaluated in patients with GDM. The main finding of the study was the presence of higher betatrophin, and GPIHBP1 levels in patients with GDM. LDL subfraction analysis also showed higher levels of small dense subfraction LDL-6 and lower mean LDL size in patients.
The serum levels of betatrophin and GPIHBP1 were found to be significantly higher in the GDM group compared to the pregnant control group in the current study. These results indicate that these markers could be a part of the adaptive mechanism of lipid metabolism against insulin resistance. In previous studies, betatrophin levels have also been found to be higher in patients with GDM [7–9]. Those studies revealed betatrophin as a risk factor for GDM, and the finding of higher levels of betatrophin in GDM patients in the current study is consistent with those results. Fenzl et al. conducted a study of type 1 diabetic patients and found a correlation between betatrophin and LDL cholesterol levels . However, no correlation between the levels of betatrophin and LDL cholesterol was determined in the current study.
To the best of our knowledge, this is the first study to have compared GPIHBP1 levels in gestational diabetes mellitus. We found higher levels of GPIHBP1 in GDM patients. These findings suggest that GPIHBP1, which plays an important role in the lipolysis of chylomicrons by binding to lipoprotein lipase enzyme, increases in response to insulin resistance .
The activity of PON1 enzyme, which is an antioxidant enzyme associated with HDL, was also investigated in this study, and no significant difference was found between the groups. Although there are no studies about gestational metabolic diseases, some studies have reported a decrease in serum PON1 activity, especially in patients with diabetes mellitus compared to a non-diabetic group [13, 14].
In the evaluation of the LDL subfractions in a study by Qiu et al, pattern B was found to be associated with a 4.9-fold increased risk of developing GDM, and the mean LDL particle size was smaller in GDM patients compared to the control group . In a study by Rizzo et al., the mean LDL size in patients with GDM was determined to be smaller than that of the control group due to decreased LDL-1, and increased LDL-4 subfractions . Sattar et al. reported higher triglycerides levels and a change in the LDL profile towards smaller and denser subfractions in line with the current study findings . Consistent with the studies mentioned above, higher levels of LDL6 subfraction and smaller mean LDL size was found in GDM patients compared to the pregnant control group in our study.
This study has some limitations to be acknowledged. First, the dietary habits of the participants were not controlled and standardized in the study. The second limitation was the small sample size of groups. Further studies with larger numbers of patients are required. Despite these limitations, this study can be considered of value with regard to determining differences in betatrophin, GPIHBP1, and LDL subfraction levels between patients and control subjects.
In conclusion, the results of this study demonstrated that betatrophin, and GPIHBP1 levels increased in GDM. LDL subfractions analysis showed that this increase was mostly due to the smaller and denser LDL subfraction (LDL6) in GDM patients. Betatrophin and GPIHBP1 are adaptive mechanisms in response to insulin resistance, and the study results suggest that betatrophin and GPIHBP1 could be potential biomarkers of metabolic syndrome in patients with GDM. There is a need for further prospective studies with larger samples to fully elucidate the mechanisms of insulin resistance in pregnancy. These biomarkers should be assessed in the postpartum period with long-term clinical outcomes such as atherosclerosis and cardiovascular diseases.