Glucose Treatment Targets in Pregnancy - A Review of Evidence and Guidelines.

BACKGROUND: Maternal diabetes mellitus during pregnancy is associated with an increased risk of pregnancy complications for both the mother and the fetus. One of the most prevalent complications is pathological fetal growth, and particularly infants are born large for gestational age (LGA), which leads to problematic deliveries, including the need for caesarean section, instrumental delivery, and further perinatal complications. Glucose monitoring during pregnancy is essential for ensuring appropriate glycaemic control and to reduce these associated risks. The current methods of glucose monitoring include measuring glycosylated haemoglobin (HbA1c), selfmonitoring of capillary blood glucose (SMBG), and more recently, continuous glucose monitoring (CGM). Observational studies and randomised controlled trials (RCTs) have assessed the appropriate glycaemic targets for HbA1c, SMBG, and CGM in relation to pregnancy outcomes. OBJECTIVE: In this review, we have identified current international guidelines on glycaemic targets and reviewed the supporting evidence. METHODS: We performed an extensive literature search on glycaemic targets in pregnancies affected by diabetes, and we researched international guidelines from recognised societies. RESULTS AND CONCLUSION: The majority of studies used to define the glucose targets associated with the best pregnancy outcomes, across all modalities, were in women with type 1 diabetes. There were limited studies on women with type 2 diabetes and gestational diabetes. We, therefore, suggest that further research needs be conducted on glucose targets and clinical outcomes, specifically in these populations where CGM technology offers the greatest potential for monitoring glucose and improving pregnancy outcomes.

Cytoplasmic long noncoding RNAs are differentially regulated and translated during human neuronal differentiation.

The expression of long noncoding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SY5Y cells. We discovered 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, 58%-70% of which are associated with polysome translation complexes. Among these polysome-associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. Fifteen of 45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea, suggesting they are under strong selective constraint in this clade. The profiling of publicly available data sets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development, and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localizes to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells, indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a noncanonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.