Circulating MicroRNA Profiles in Pregnant South African Women with Different Types of Diabetes Mellitus

Abstract

Diabetes in pregnancy increases the risk of adverse perinatal outcomes for mother and child, with severity influenced by the type of diabetes and degree of hyperglycemia. This study aimed to identify circulating microRNAs (miRNAs) associated with different types of diabetes in pregnancy. Serum miRNAs were profiled in pregnant South African women with type 1 diabetes (T1DM), type 2 diabetes (T2DM), gestational diabetes (GDM), and normoglycemia using PCR arrays (n = 15). Differentially expressed miRNAs were validated in pregnant South African women (n = 167), and a separate cohort of Spanish pregnant women with T1DM and T2DM (n = 48). PCR arrays showed significant differential expression for miR-19b-3p (down arrow 9.8-fold; p = 0.033) in GDM, miR-20a-5p (down arrow 4.5-fold; p = 0.047) in T1DM, and miR-29a-3p (up arrow 1.8-fold; p = 0.002) in T2DM compared to normoglycemia. Screening in the larger cohort showed lower expression of miR-20a-5p (down arrow 2-fold; p = 0.013) in GDM and miR-30d-5p (down arrow 2.1-fold; p = 0.032) in T1DM compared to normoglycemia. Additionally, miR-20a-5p levels were higher in women with T2DM compared to those with GDM (up arrow 2.5-fold; p = 0.019). Our findings show that miRNA profiles are largely consistent across different types of diabetes in pregnancy, suggesting that hyperglycemia plays a key role in shaping miRNA expressions. Moreover, the identification of several shared gene targets suggests common underlying pathophysiological mechanisms.