High serum total bilirubin as a potential protective factor for gestational diabetes mellitus: a retrospective cohort study of 92,885 Chinese pregnant women

Gestational diabetes mellitus (GDM) is one of the most prevalent metabolic disorders in pregnancy, affecting 5-25% of pregnant women worldwide [1], [2], [3]. It imposes short- and long-term adverse consequences for both mothers and their children. Women with previous GDM are more prone to develop cardiovascular diseases, metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) later in life [4], [5], [6]. Offspring born to GDM mothers are more likely to experience adverse birth outcomes and are at higher risk of developing metabolic and cardiovascular diseases in adulthood [7], [8], [9]. Therefore, it is crucial to identify physiological factors that reduce pregnant women's risk for developing GDM.

Bilirubin, a natural product of heme catabolism, is useful for assessing liver function, and high serum total bilirubin (TBIL) levels serve as a marker of hepatobiliary disorders [10]. However, within the physiologically normal range, bilirubin exhibits potent antioxidative activity and offers protection against oxidative stress [11,12]. Oxidative stress may play a role in pathogenesis of T2DM [13], [14], [15]. Reports from several studies have indicated inverse associations between serum levels of TBIL and risk of T2DM [16], [17], [18], [19], [20]. However, only very few studies with small sample sizes have examined the associations between serum TBIL and GDM, and the results were inconsistent [21], [22], [23], [24].

In this study, we sought to examine whether higher serum levels of TBIL were associated with a decreased risk of GDM in a large cohort of pregnant Chinese women. We hope our findings will clarify the pathophysiological significance of bilirubin in the prevention of GDM.

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