PCOS is a risk factor for GDM and was confirmed in a study by Weerakiet S more than 10 years ago [1]. GDM has many effects on both pregnancy outcomes and long-term neonatal complications. The same validation was obtained in the study by Toulis KA [2]. A meta-analysis performed by Jing Z found that the incidence of GDM was reduced by using metformin, suggesting that metformin is effective for preventing GDM in PCOS patients. Therefore, the risk factors for GDM in PCOS women can guide clinicians to early prevention and intervention to reduce occurrence [3]. In our study, we combined five independent risk factors, including BMI, HbA1C, age, TC, and family history, to construct a nomogram model to predict the risk of GDM in women with PCOS in their first trimester.
Type 2 diabetes exhibits insulin resistance and elevated blood glucose levels, which may promote pathological harm in PCOS patients [18]. It is generally accepted that Fatty acids(FAs) play a major role in the development of insulin resistance[19]. In our study, TC is the positive index to indicate the occurrence of GDM in pregnant women with PCOS. Several studies have reported that dyslipidemia in the first trimester of pregnancy is related to the development of GDM [20, 21]. Lean or obese women with higher TG concentrations have an increased risk of developing GDM, whereas lean women with high HDL-C levels do not. This statement is consistent with O’Malley, who stated that maternal obesity mediates the epidemiological relationship between GDM and dyslipidemia, and only women with GDM who were obese had higher TG and lower HDL-C levels and a higher TG: HDL-C ratio than those without GDM [22]. A retrospective study indicated that women with GDM are more likely to have hyperlipidemia postpartum, particularly dyslipidemia defined by TG [23]. Hyperinsulinemia is usually concomitant with low HDL cholesterol and high LDL–cholesterol levels. The increased release of free fatty acids from insulin-resistant fat cells may be the cause of these characteristics [24]. Dyslipidemia, which is associated with diabetes mellitus, is the main risk factor for the development of cardiovascular disease. Diabetes-related lipid changes are attributed to an increased free fatty acid flux caused by insulin resistance. However, the varies of TG was not included in our nomogram model, it may attributed to the different value units and classification of grading methods.
HbA1c is also an indicator for Abnormal glucose regulation, to enable early recognition and intervention of GDM. Based on the prospective analysis for 1,989 pregnant women, Yi-Ran Ho etc. conluded that the when the level of HbA1c achive to 5.7%, the AUC(Area Under The Curve) of the ROC curvce was 0.70 and significantly associated with increased risks of neonatal complications like neonatal intensive care unit, low birth weight, and macrosomia[28]. Burke Schaible etc. showed that HbA1C also was a reliable indicator to GDM for pregnant women in first trimester. They included 146 patients and recommended that an HbA1c threshold of 5.15% can identify 66.7% of pregnant women with abnormal oral glucose tolerance test at 24–28 weeks[29]. While, a large cohort study in China demonstrated that the HbA1c test offers limited value in GDM diagnoses. A total of 19,261 pregnant were enrolled in this study, and Yi Lai et al. found that level of HbA1c is 5.0% as the cutoff point, the sensitivity and specificity was 60.1% and 65.3% respectively. It maybe attributed that the HbA1 level changes is delayed to identify certain cardiometabolic changes. In our study, logistic regression result shows that the level of HbA1c is the significant factor to predict GDM. Consequently, it would be useful to have a clinical index that could quantify the differences between women with PCOS who have GDM and those who do not have. It was shown that both insulin sensitivity and β-cell function are significantly decreased with a 0.6% increase in glycohemoglobin and that insulin resistance can be found by detecting HbA1C [13].
In our study, BMI is the significant index to indicate the occurrence of GDM in pregnant women with PCOS. N.S. Kakoly pointed out that obese women with PCOS patients are more likely to develop insulin resistance or type 2 diabetes mellitus later, and this results were independent of race[20]. According to previous studies, the most important risk factor for GDM is being overweight or obese prior to pregnancy (BMI 25 kg/m2 or above) [21]. This was not affected by the geographical distribution, parity, or a history of GDM. However, a previously reported clinical model that used BMI as the independent factor to screen for GDM found that the outcomes varied widely by race: GDM was found in more than 76% of African-Americans, 58% of Latinas, and 46% of Caucasians, but only 25% of Asians (p = 0.001) [22]. A meta-analysis estimated that the risk of developing GDM increases with weight gain and is not affected by location; compared to the control group, the risk of developing GDM is approximately two, four, and eight times higher in overweight, obese, and extremely obese women, respectively [23].
Recently, much attention has been paid to the role of other hormone factors in the development of GDM. The prediction indices included Follicle-Stimulating Hormone(FSH), Luteinizing Hormone(LH), and Thyroid peroxidase antibody (TPA). The prediction time includes the first and second trimester of pregnancy, but there is no simple and practical prediction index with high sensitivity and specificity. Therefore, we should consider other parameters for predicting GDM in women with PCOS.
We conclude that insulin, age, TC, HbA1C, and family history were effective risk predictors for GDM in women with PCOS in the first trimester. Our analysis was limited because all data used for analysis were obtained from a single site, which may have impaired our analysis. A multicenter validation using a large number of patients may produce results that are more generalizable to the broader population.