Diabetes Mellitus and Cardiovascular Risk Assessment in Mothers with a History of Gestational Diabetes Mellitus Based on Postpartal Expression Profile of MicroRNAs Associated with Diabetes Mellitus and Cardiovascular and Cerebrovascular Diseases

Abstract

Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3-11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

Keywords: cardiovascular risk; cardiovascular/cerebrovascular diseases; gestational diabetes mellitus; microRNA expression; mothers; pregnancy complications; primary prevention; screening.

Figure 1

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. MicroRNA gene expression data (2^−ΔΔCt) are visualized using the heat map. In this setting, each row represents a sample (GDM1–GDM111, NP1–NP89) and each column represents a microRNA gene. The color and intensity of the boxes are used to represent changes of gene expression (2^−ΔΔCt). Green color indicates upregulation, and red color indicates downregulation. NP, normal pregnancies.

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 2

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies. (A–Z) Upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and miR-574-3p was observed in mothers after GDM pregnancies when the comparison to the controls was performed using Mann–Whitney test. Receivers operating characteristic (ROC) curves were constructed to calculate the area under the curve (AUC), the best cut-off point (criterion), the sensitivity, specificity, likelihood ratio positive (LR+), and likelihood ratio negative (LR−) for particular microRNA. In addition, respective sensitivity at 90.0% specificity was reported for miR-1-3p (43.24%), miR-16-5p (20.72%), miR-17-5p (21.62%), miR-20a-5p (10.81%), miR-20b-5p (38.74%), miR-21-5p (28.83%), miR-23a-3p (17.12%), miR-24-3p (0.90%), miR-26a-5p (20.72%), miR-29a-3p (21.62%), miR-100-5p (13.51%), miR-103a-3p (30.63%), miR-125b-5p (9.91%), miR-126-3p (9.91%), miR-130b-3p (3.60%), miR-133a-3p (18.92%), miR-143-3p (13.51%), miR-145-5p (7.21%), miR-146a-5p (17.12%), miR-181a-5p (31.53%), miR-195-5p (16.22%), miR-199a-5p (15.32%), miR-221-3p (31.53%), miR-342-3p (1.8%), miR-499a-5p (28.83%), and miR-574-3p (10.81%).

Figure 3

Combined postpartal screening of microRNAs in the identification of mothers with a history of GDM at an increased cardiovascular risk. Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of diabetes mellitus, and cardiovascular/cerebrovascular diseases.

Figure 4

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies with regard to the treatment strategies. (A–O) Upregulation or trend towards upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p was observed in mothers after GDM pregnancies regardless of the treatment strategies (diet only and/or the combination of diet and therapy). (P) Upregulation of miR-133a-3p was observed in mothers after GDM pregnancies on diet only.

Figure 4

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies with regard to the treatment strategies. (A–O) Upregulation or trend towards upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p was observed in mothers after GDM pregnancies regardless of the treatment strategies (diet only and/or the combination of diet and therapy). (P) Upregulation of miR-133a-3p was observed in mothers after GDM pregnancies on diet only.

Figure 4

Postpartal microRNA expression profile in mothers with a history of GDM pregnancies with regard to the treatment strategies. (A–O) Upregulation or trend towards upregulation of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p was observed in mothers after GDM pregnancies regardless of the treatment strategies (diet only and/or the combination of diet and therapy). (P) Upregulation of miR-133a-3p was observed in mothers after GDM pregnancies on diet only.