Source: idiabetes
Gestational diabetes mellitus (GDM) is a common gestational abnormal glucose metabolism and is associated with a variety of adverse pregnancy outcomes, including pre-eclampsia, macrosomia and neonatal hypoglycemia . At the same time, GDM increases the risk of cardiovascular disease and 2 diabetes after delivery. More and more evidences suggest that thyroid dysfunction and autoimmune thyroid disease may be related to the pathogenesis of GDM, but the relationship is controversial. To this end, Luo Jingyi, a postdoctoral fellow in the team of Professor Guo Lixin from Beijing Hospital , and others conducted a systematic evaluation of the relationship between thyroid disease and GDM risk through Meta-analysis .
The research team conducted a comprehensive search of relevant studies up to November 2020 in PubMed, Embase, MEDLINE and Cochrane databases, and used the Newcastle-Ottawa scale to assess the quality of all included studies. Finally, a total of 44 studies were included in this meta-analysis.
The results of the study
01, thyroid autoantibodies and GDM
Meta analysis showed that thyroid autoantibodies were closely related to the risk of GDM (OR 1.49, 95%CI: 1.07~2.07, P%1<0.00001,>1I).Subgroup analysis showed that thyroid peroxidase antibody (TPOAb, OR 1.65, 95%CI: 1.13~2.40, P<0.00001,>I2=74%) or thyroglobulin antibody (TgAb, OR 1.88, 95%CI: 1.13~3.12, P=0.02, I2=0%) positive were all related to the increased risk of GDM (Figure 1). The results suggest that women with autoimmune thyroiditis should pay great attention to blood glucose monitoring during pregnancy if they become pregnant.
Figure 1. Forest map of thyroid autoantibody positive ：1.73~1.86，PI2=24%）和1.54（95%CI：1.03~2.30，P=0.03，I2=86%）（图2）。 These results suggest that high levels of thyroid-stimulating hormone (TSH) can increase the risk of GDM even when thyroid hormone levels are in the normal range. Therefore, for patients with hypothyroidism, regardless of whether there are clinical symptoms or abnormal thyroid hormone levels, the monitoring of blood glucose during pregnancy should not be ignored.
Figure 2. Forest map of the risk relationship between hypothyroidism and GDM ，P=0.01，I2=0%），而亚临床甲亢则与GDM发生风险降低相关（OR 0.62，95%CI：0.39~0.97，P=0.04，I2=32%)（图3）。 The results of this study on subclinical hyperthyroidism are currently controversial, and large sample studies need to be included and analyzed in the future.
Figure 3. Forest map of the risk relationship between hyperthyroidism and GDM.
Discussion
A total of 44 studies were included in this study, which provides evidence support for the possible impact of thyroid disease on the occurrence of GDM in pregnant women.
Decreased serum free thyroxine (FT4) levels in pregnant women in the first and second trimesters may increase the risk of GDM. At the same time, pregnant women with hypothyroxinemia had a significantly higher risk of GDM. Because the thyroid hormone required by the fetus is completely dependent on the mother in early pregnancy, insufficient serum FT4 levels in pregnant women will lead to serious adverse consequences. At the same time, there is evidence that low serum FT4 levels are strongly associated with metabolic syndrome and insulin resistance .
Hypothyroidism is a common endocrine disease. In pregnant women, the prevalence of clinical and subclinical hypothyroidism is 0.5% and 2% to 3%, respectively. Our meta-analysis found that clinical hypothyroidism and subclinical hypothyroidism were associated with an increased risk of GDM.A study showed that oxidative stress is associated with hypothyroidism, and oxidative stress is also an important link in the pathogenesis of diabetes. In addition, elevated TSH can induce the release of certain inflammatory factors, thereby enhancing the process of oxidative stress, and elevated TSH levels may be involved in the process of clinical hypothyroidism and subclinical hypothyroidism increasing the risk of GDM.
The meta-analysis found that clinical hyperthyroidism was also associated with an increased risk of GDM; but surprisingly, subclinical hyperthyroidism reduced the risk of GDM. Tudela et al. also found this result in a study of 24 355 subjects, but their team was unable to elaborate on the underlying mechanism and possible reasons, and the relevant mechanism needs to be further studied.
Elevated levels of thyroid autoantibodies are associated with adverse pregnancy outcomes such as miscarriage, pregnancy-induced hypertension , premature rupture of membranes and low birth weight. The analysis of thyroid autoantibodies in this study showed that both TPOAb and TgAb were associated with an increased risk of GDM. TPO and Tg play an important role in the production and secretion of thyroid hormones, and their antibodies can be detected in 10% to 20% of women of reproductive age. One study showed that TPOAb in in peripheral blood of Hashimoto's thyroiditis patients was inversely correlated with β-cell homeostasis, and the reduction of CD19+CD24hiCD38hi Breg cells in peripheral blood samples increased the risk of insulin resistance [6]. Another study suggested that elevated thyroid antibodies increase the release of inflammatory cytokines, leading to insulin resistance and diabetes [7]. The specific mechanism needs to be further studied and clarified.
Conclusion
The existing research results show that abnormal thyroid function and positive thyroid antibodies are potentially associated with the occurrence of GDM, which can be summarized as positive TPOAb/TgAb, clinical and subclinical hypothyroidism, and clinical hyperthyroidism.This suggests that providing comprehensive GDM screening for pregnant women with thyroid disease and paying attention to their abnormal glucose metabolism has certain clinical value in improving their adverse pregnancy outcomes.
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