Circulating miR-330-3p in Late Pregnancy is Associated with Pregnancy Outcomes Among Lean Women with GDM

Abstract

Gestational Diabetes Mellitus (GDM) is characterised by insulin resistance accompanied by reduced beta-cell compensation to increased insulin demand, typically observed in the second and third trimester and associated with adverse pregnancy outcomes. There is a need for a biomarker that can accurately monitor status and predict outcome in GDM, reducing foetal-maternal morbidity and mortality risks. To this end, circulating microRNAs (miRNAs) present themselves as promising candidates, stably expressed in serum and known to play crucial roles in regulation of glucose metabolism. We analysed circulating miRNA profiles in a cohort of GDM patients (n = 31) and nondiabetic controls (n = 29) during the third trimester for miRNA associated with insulin-secretory defects and glucose homeostasis. We identified miR-330-3p as being significantly upregulated in lean women with GDM compared to nondiabetic controls. Furthermore, increased levels of miR-330-3p were associated with better response to treatment (diet vs. insulin), with lower levels associated with exogenous insulin requirement. We observed miR-330-3p to be significantly related to the percentage of caesarean deliveries, with miR-330-3p expression significantly higher in spontaneously delivered GDM patients. We report this strong novel association of circulating miR-330-3p with risk of primary caesarean delivery as a pregnancy outcome linked with poor maternal glycaemic control, strengthening the growing body of evidence for roles of diabetes-associated miRNAs in glucose homeostasis and adaptation to the complex changes related to pregnancy. Gestational Diabetes Mellitus (GDM) is diagnosed as the development of hyperglycaemia during the second or third trimester in pregnant women not previously diagnosed with diabetes 1. The global epidemic of obesity and diabetes has resulted in an increase in the prevalence of diabetes mellitus in women of childbearing age and estimates currently place 5% to 20% of pregnancies as affected by GDM worldwide, due to differences in population demographics, diagnostic criteria, screening methods and maternal lifestyle 2. The significant risk-associations between hyperglycaemia not considered to be within the diagnostic range for overt diabetes and adverse perinatal and maternal outcomes require more accurate measures for monitoring status and predicting outcome in GDM 3. The pathophysiology of GDM manifests as a result of the progressive insulin resistance (IR) and subsequent increased insulin secretion requirement that occurs during normal pregnancy 4. As a result, most women with GDM develop pancreatic beta-cell dysfunction secondary to IR, resulting in impaired glucose tolerance in a setting of IR similar to that of T2DM 5. However, the possible causes of beta-cell dysfunction and IR are not well described, including the contributions of autoimmune and monogenic factors. Meta-analysis of gene expression profiles has indicated that the transcriptome profile in GDM is more similar to that of autoimmune type 1 diabetes mellitus (T1DM...

Postpartum circulating microRNA enhances prediction of future type 2 diabetes in women with previous gestational diabetes

“…Interestingly, in this study there were two subgroups of women with GDM (based on miR-330-3p expression), and the subgroup with relatively higher levels of miR-330-3p had lower fasting insulin and higher incidence of Caesarean section deliveries [49]. In a recent study, higher miR-330-3p levels in the third trimester of pregnancy were reported to be associated with lower exogenous insulin supplementation and better response to GDM management therapy as well as a higher number of vaginal deliveries in women with GDM [50]. The differences observed in the miRNA expression profiles between these different studies could be attributed to type of biofluid, stage of pregnancy for sample collection, ethnicity, age, BMI and smoking status of enrolled participants.…”

Circular RNA expression profiles in umbilical cord blood exosomes from normal and gestational diabetes mellitus patients

“…In our study, we found that most of the exosomal circRNAs harbored miRNA-binding sites, and some miRNAs were associated with GDM. For example, miR-330, miR-23a, and miR-16-5p were reported to be up-regulated in the plasma of GDM patients [ 29–32 ]. miR-330, miR-23a and miR-16-5p were matched with circ_0092108, which was verified to down-regulated in umbilical cord blood exosomes of GDM patients.…”

Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus

“…Another study through ROC analysis showed that the AUC was 0.927 for miR-185 with a sensitivity and specificity of 0.865 and 0.838, respectively, indicating serum miR-185 differentiated patients with GDM from healthy controls ( 123 ). Moreover, miR-330-3p ( 18 , 24 – 32 ) was identified as being significantly upregulated in lean women with GDM compared to nondiabetic pregnant women during the third trimester, highlighting miR-330-3p as a possible new biomarker ( 120 ). Furthermore, a significant decrease occurred in the expression levels of miR-21-3p during the third trimester in GDM patients compared with healthy controls, whose AUC in GDM was 0.73 ( 121 ).…”