The prevalence of diabetes mellitus is increasing in resource limited settings. Simultaneously, there has been an increase in the number of novel therapies for the management of diabetes mellitus. However, use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings. Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes, and thus most likely to benefit from the therapy, are less likely to have negative budget impact for funders. To improve access, and reduce morbidity and mortality, requires alignment amongst key stakeholders including patient advocacy groups, health care professional councils, national departments of health, the pharmaceutical industry, treasury and finance departments.

Background: Analysis of placental genes could unravel maternal-fetal complications. However, inaccessibility to placental tissue during early pregnancy has limited this effort. We tested if exosomes (Exo) released by human placenta in the maternal circulation harbor crucial placental genes.Methods: Placental alkaline phosphate positive exosomes (ExoPLAP) were enriched from maternal blood collected at the following gestational weeks; 6–8th (T1), 12–14th (T2), 20–24th (T3), and 28th−32nd (T4). Nanotracking analysis, electron microscopy, dynamic light scattering, and immunoblotting were used for characterization. We used microarray for transcriptome and quantitative PCR (qPCR) for gene analysis in ExoPLAP.Results: Physical characterization and presence of CD63 and CD9 proteins confirmed the successful ExoPLAP enrichment. Four of the selected 36 placental genes did not amplify in ExoPLAP, while 32 showed regulations (n = 3–8/time point). Most genes in ExoPLAP showed significantly lower expression at T2–T4, relative to T1 (p < 0.05), such as NOS3, TNFSF10, OR5H6, APOL3, and NEDD4L. In contrast, genes, such as ATF6, NEDD1, and IGF2, had significantly higher expression at T2–T4 relative to T1. Unbiased gene profiling by microarray also confirmed expression of above genes in ExoPLAP-transcriptome. In addition, repeated measure ANOVA showed a significant change in the ExoPLAP transcriptome from T2 to T4 (n = 5/time point).Conclusion: Placental alkaline phosphate positive exosomes transcriptome changed with gestational age advancement in healthy women. The transcriptome expressed crucial placental genes involved in early embryonic development, such as actin cytoskeleton organization, appropriate cell positioning, DNA replication, and B-cell regulation for protecting mammalian fetuses from rejection. Thus, ExoPLAP in maternal blood could be a promising source to study the placental genes regulation for non-invasive monitoring of placental health.

Background: Renal disease in T2DM could arise independent of hyperglycemia, aka non diabetic kidney disease. Their prevalence ranges from 33%to72.5% among T2DM patients. Specific molecular signatures that distinguish Diabetic Nephropathy from NDKD (FSGS) in T2DM might provide new targets for CKD management. Methods: Five original GEO microarray DN and FSGS datasets were evaluated (GSE111154, GSE96804, GSE125779, GSE129973 and GSE121233). Each of the three groups (DN, FSGS, and Controls) had equal renal transcriptome data (n=32) included in the analysis to eliminate bias. The DEGs were identified using TAC4.0. Pathway analysis was performed on the discovered genes that aligned to official gene symbols using Reactome, followed by functional gene enrichment analysis using Funrich,Enrichr. STRING and Network analyst investigated PPI, followed by Webgestalt's pathway enrichment. Finally, using the Targetscan7.0 and DIANA tools, filtered differential microRNAs downregulated in DN were evaluated for target identification. Result: Between the three groups, DN, FSGS, and Control, a total of 194 DEGs. with foldchange >2& <-2 and P-value0.01 were found in the renal transcriptome. In comparison to control, 45 genes were elevated particularly in DN, whereas 43 were upregulated specifically in FSGS. DN datasets were compared to FSGS in a separate analysis. FABP4, EBF1, ADIRF, and ART4 were shown to be among the substantially up-regulated genes unique to DN in both analyses. The transcriptional regulation of white adipocytes was discovered by a pathway analysis. Conclusion: The molecular markers revealed might be employed as specific targets in the aetiology of DN, as well as in T2DM patients' therapeutic care.

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