Diabetes is one of the most frequently occurring metabolic disorders, affecting almost one tenth of the global population. Despite advances in antihyperglycemic therapeutics, the management of diabetes is limited due to its complexity and associated comorbidities, including diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are involved in the regulation of gene expression as well as various disease pathways in humans. Several ncRNAs are dysregulated in diabetes and are responsible for modulating the expression of various genes that contribute to the ‘symptom complex’ in diabetes. We review various miRNAs and lncRNAs implicated in diabetes and delineate ncRNA biological networks as well as key ncRNA targets in diabetes. Further, we discuss the spatial regulation of ncRNAs and their role(s) as prognostic markers in diabetes. We also shed light on the molecular mechanisms of signal transduction with diabetes-associated ncRNAs and ncRNA-mediated epigenetic events. Lastly, we summarize clinical trials on diabetes-associated ncRNAs and discuss the functional relevance of the dysregulated ncRNA interactome in diabetes. This knowledge will facilitate the identification of putative biomarkers for the therapeutic management of diabetes and its comorbidities. Taken together, the elucidation of the architecture of signature ncRNA regulatory networks in diabetes may enable the identification of novel biomarkers in the discovery pipeline for diabetes, which may lead to better management of this metabolic disorder.

Understanding how HIV-1 pathogenesis affects systemic and TB specific immunity in the setting of latent (LTBI+) compared to active TB infection could provide actionable insights for the prevention of reactivation. Fifty HIV-seronegative and 112 HIV-1-positive anti-retroviral therapy (ART)-naïve participants were stratified as LTBI+ (n = 35), active TB+ (n = 22) and non-coinfected (n = 55) based on an interferon gamma release assay (IGRA) and clinical confirmation prior to receiving TB therapy. Systemic and TB-specific (DosR and Rpf) immune monitoring of cellular subsets, together with multi-analyte plasma analysis, was carried out. Pursuant to isoniazid prophylaxis therapy (IPT) and ART initiation, HIV-1-positive LTBI+ participants (HLTBI+) were followed for up to two years. Before ART initiation, HLTBI+ individuals exhibited the lowest levels of circulating intermediate monocytes, T-cell activation and PD-1 expression, with a decreased frequency of T-regulatory cells and higher circulating IL-10 and IL-17A. PD-1 expression on CD4+ T cell memory subsets, together with opposing anamnestic TNF-α responses to DosR and Rpf, was a discriminatory signature for the HLTBI+ group, as was preserved (following ART) TB-specific TNF-α production, which positively correlated with the CD4/CD8 ratio. Our results highlight an immunomodulatory phenotype conferred by latent TB infection in PLHIV, whose preservation may provide strategies to mitigate TB reactivation.