Different types of small non-coding RNAs, especially microRNAs (miRNAs), may be found in the circulation, either protein bound or enclosed in extracellular vesicles. During gestation, and particular during gestational diabetes mellitus (GDM), the levels of several miRNAs are altered. Worldwide the incidence of GDM is increasing, in part driven by the current obesity epidemic. This is a point of public health concern, because offspring of women with GDM frequently suffer from short and long-term complications of maternal GDM. This has prompted the investigation of whether levels of specific miRNA species, detected early in gestation, may be used as diagnostic or prognostic markers for development of GDM. Here, we summarize mechanisms of RNA secretion, and review circulating miRNAs associated with GDM. Several miRNAs are associated with GDM: miR-29a-3p and miR-29b-3p are generally upregulated in GDM pregnancies, also when measured prior to the development of GDM, while miR-16-5p is consistently upregulated in GDM pregnancies, especially in late gestation. miR-330-3p in circulation is increased in late gestation GDM women, especially in those with poor insulin secretion. miR-17-5p, miR-19a/b-3p, miR-223-3p, miR-155-5p, miR-125-a/b-5p, miR-210-3p and miR-132 are also associated with GDM, but less so and with more contradictory results reported. There could be a publication bias as miRNAs identified early are investigated the most, suggesting that it is likely that additional, more recently detected miRNAs could also be associated with GDM. Thus, circulating miRNAs show potential as biomarkers of GDM diagnosis or prognosis, especially multiple miRNAs containing prediction algorithms show promise, but further studies are needed.

Gestational diabetes mellitus (GDM) is a severe pregnancy complication for both the woman and the child. Women who suffer from GDM have a greater risk of developing Type 2 diabetes mellitus (T2DM) later in life. Identification of any potential biomarkers for the early prediction of gestational diabetes can help prevent the disease in women with a high risk. Studies show microRNA (miRNA) as a potential biomarker for the early discovery of GDM, but there is a lack of clarity as to which miRNAs are consistently altered in GDM. This study aimed to perform a systematic review and meta-analysis to investigate miRNAs associated with GDM by comparing GDM cases with normoglycemic controls. The systematic review was performed according to PRISMA guidelines with searches in PubMed, Web of Science, and ScienceDirect. The primary search resulted in a total of 849 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 35 full-text articles, which were evaluated for risk of bias and estimates of quality, after which data were extracted and relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: MiR-29a, miR-330, miR-134, miR-132, miR-16, miR-223, miR-155, miR-122, miR-17, miR-103, miR-125, miR-210, and miR-222. While some miRNAs showed considerable between-study variability, miR-29a, miR-330, miR-134, miR-16, miR-223, and miR-17 showed significant overall upregulation in GDM, while circulating levels of miR-132 and miR-155 were decreased among GDM patients, suggesting further studies of these as biomarkers for early GDM discovery.