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Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application.

ABSTRACT: Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring.

SUBMITTER: Ibarra A

PROVIDER: S-EPMC6316501 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application.

Ibarra Adriana A Vega-Guedes Begoña B Brito-Casillas Yeray Y Wägner Ana M AM

Non-coding RNA 20181112 4

Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with incre ...[more]

PMID: 30424584

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Project description:AIMS:Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex. METHODS:In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI?25kg/m2) or lean (ppBMI<25kg/m2) women, and women with male or female offspring separately. RESULTS:Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (?=0.260/p=0.028) and -21-3p (?=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (?=0.266/p=0.068) and miR-517-5p (?=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p<0.05). CONCLUSIONS:Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

Project description:FMRI-studies are mostly based on a group study approach, either analyzing one group or comparing multiple groups, or on approaches that correlate brain activation with clinically relevant criteria or behavioral measures. In this study we investigate the potential of fMRI-techniques focusing on individual differences in brain activation within a test-retest reliability context. We employ a single-case analysis approach, which contrasts dyscalculic children with a control group of typically developing children. In a second step, a support-vector machine analysis and cluster analysis techniques served to investigate similarities in multivariate brain activation patterns. Children were confronted with a non-symbolic number comparison and a non-symbolic exact calculation task during fMRI acquisition. Conventional second level group comparison analysis only showed small differences around the angular gyrus bilaterally and the left parieto-occipital sulcus. Analyses based on single-case statistical procedures revealed that developmental dyscalculia is characterized by individual differences predominantly in visual processing areas. Dyscalculic children seemed to compensate for relative under-activation in the primary visual cortex through an upregulation in higher visual areas. However, overlap in deviant activation was low for the dyscalculic children, indicating that developmental dyscalculia is a disorder characterized by heterogeneous brain activation differences. Using support vector machine analysis and cluster analysis, we tried to group dyscalculic and typically developing children according to brain activation. Fronto-parietal systems seem to qualify for a distinction between the two groups. However, this was only effective when reliable brain activations of both tasks were employed simultaneously. Results suggest that deficits in number representation in the visual-parietal cortex get compensated for through finger related aspects of number representation in fronto-parietal cortex. We conclude that dyscalculic children show large individual differences in brain activation patterns. Nonetheless, the majority of dyscalculic children can be differentiated from controls employing brain activation patterns when appropriate methods are used.

Project description:BackgroundFor women with pre-existing and gestational diabetes mellitus, pregnancy involves specialized and intensive medical care to improve maternal and infant outcomes. Medical management for patients with diabetes in pregnancy typically occurs via frequent face-to-face outpatient appointments. Barriers to face-to-face care during the COVID-19 pandemic have signaled the need for high-quality, patient-centered virtual health care modalities, such as mobile health (mHealth).ObjectiveThe objective of the proposed scoping review is to identify the patient-reported benefits and limitations of mHealth technology among women with diabetes in pregnancy. We also aim to determine how the women's experiences align with the best practice standards for patient-centered communication.MethodsArksey and O'Malley's framework for conducting scoping reviews with refinements by Levac et al will be used to guide the conduct of this scoping review. Relevant studies will be identified through comprehensive database searches of MEDLINE, Embase, Emcare, and PsycINFO. Following database searches, studies will be screened for eligibility at the title, abstract, and full-text level by two independent reviewers, with the inclusion of a third reviewer if required to reach consensus. Data charting of included studies will be conducted by one reviewer using a standardized data extraction form and verified independently by a second reviewer. Synthesis of results will be guided by Thomas and Harden's "Methods for the Thematic Synthesis of Qualitative Research in Systematic Reviews."ResultsAs of August 2020, we have carried out the qualitative searches in the electronic databases MEDLINE, Embase, Emcare, and PsycINFO (Ovid interface) for a combined total of 8207 articles. Next, we plan to conduct the quantitative searches in the electronic databases MEDLINE, Embase, and Emcare (Ovid interface). We also plan to review the reference lists of relevant studies to identify additional eligible studies.ConclusionsWith the results of this review, we hope to describe the patient-reported benefits and limitations of mHealth technology for women with diabetes in pregnancy. Furthermore, we aim to determine how women's experiences align with the best practice standards for patient-centered communication. Ultimately, our review can provide valuable information for guideline developers, policy makers, and clinicians related to mobile technologies to support virtual care delivery for women with diabetes in pregnancy.International registered report identifier (irrid)PRR1-10.2196/29727.

Dataset Information

Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application.

Publications

Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application.

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