Adiponectin DNA methylation in South African women with gestational diabetes mellitus : effects of HIV infection

DNA methylation is increasingly recognized as a potential biomarker of metabolic disease. However, there is limited information on the impact of human immunodeficiency virus (HIV) infection on the candidacy of DNA methylation to serve as molecular biomarkers. This study investigated the effect of HIV infection on DNA methylation patterns in the peripheral blood of South African women with (n = 95) or without (n = 191) gestational diabetes mellitus (GDM). DNA methylation levels at eight CpG sites in the adiponectin gene (ADIPOQ) promoter were measured using bisulfite conversion and pyrosequencing. Differences between HIV negative ( - ) and positive ( + ) women were observed. In HIVwomen, methylation at CpG -3400 was lower in GDM+ women compared to those with normoglycemia (8.5-fold; p = 0.004), and was associated with higher fasting glucose (β-co-efficient = 0.973; p = 0.006) and lower adiponectin (β-co-efficient = -0.057; p = 0.014) concentrations. These associations were not observed in HIV+ women. In silico analysis showed that Transcription Factor AP2-alpha is able to bind to the altered CpG site, suggesting that CpG -3400 may play a functional role in the regulation of ADIPOQ expression. Our findings show that DNA methylation differs by HIV status, suggesting that HIV infection needs to be taken into consideration in studies exploring DNA methylation as a biomarker of GDM in high HIV prevalence settings.http://www.plosone.orgpm2022Internal MedicineObstetrics and Gynaecolog

Molecular biomarkers for gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included “gestational diabetes mellitus”, “blood”, “single-nucleotide polymorphism (SNP)”, “DNA methylation”, and “microRNAs”, including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.http://www.mdpi.com/journal/ijmsInternal MedicineObstetrics and Gynaecolog

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response

Abstract Background There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity. We used semi-automated, whole lung quantification of lung lesions to analyse serial FDG PET-CT scans from the Catalysis TB Treatment Response Cohort to identify characteristics that best correlated with clinical and microbiological outcomes. Results Quantified scan metrics were already associated with clinical outcomes at diagnosis and 1 month after treatment, with further improved accuracy to differentiate clinical outcomes after standard treatment duration (month 6). A high cavity volume showed the strongest association with a risk of treatment failure (AUC 0.81 to predict failure at diagnosis), while a suboptimal reduction of the total glycolytic activity in lung lesions during treatment had the strongest association with recurrent disease (AUC 0.8 to predict pooled unfavourable outcomes). During the first year after TB treatment lesion burden reduced; but for many patients, there were continued dynamic changes of individual lesions. Conclusions Quantification of FDG PET-CT images better characterised TB treatment outcomes than qualitative scan patterns and robustly measured the burden of disease. In future, validated metrics may be used to stratify patients and help evaluate the effectiveness of TB treatment modalities