Diabetes, Lipids and Metabolism Laboratory
PROJECTS IN ASSOCIATION
New oxidative pathway of DNA demethylation: diabetes hyperglycemic effect in global DNA methylation and hydroxymethylation
Current status: Active
Background: Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycemia and increased oxidative stress that could lead to chronic micro- and macro-vascular complications. We hypothesized that part of the target organ damage is mediated by alterations in epigenetic mechanisms.
Methods: We analyzed global DNA methylation and hydroxymethylation in peripheral blood in 79 subjects: 19 well-controlled and 25 poorly controlled patients with T2DM, and 35 healthy controls. We also analyzed microarrays of DNA methylation and gene expression in other tissues from the GEO database repository.
Results: DNA methylation and hydroxymethylation levels were increased in poorly-controlled patients compared to well-controlled and healthy individuals (p=0.0039 for 5mC, p=0.0034 for 5hmC). Both 5mC and 5hmC correlate well with glycated hemoglobin (HbA1c %) (r=0.29, p=0.009 and r=0.219, p=0.05), indicating an association with changes in the epigenome. In methylation microarrays, 5mC in peripheral blood were higher in T2DM vs. controls; in pancreas and other tissues 5mC and 5hmC levels were the opposite of blood. The high levels of 5mC and 5hmC were not explained by different expression of genes involved in the demethylation machinery (TET enzymes), but one enzyme involved in DNA repair (AID) was found to be increased in T2DM pancreas (p=0.017).
Conclusions: The oxidation associated with hyperglycemia in T2DM may explain the DNA demethylation observed in many tissues, although this DNA demethylation was only observed in tissues with increased expression of genes associated with DNA repair machinery and not blood. This suggest a new pathway for DNA demethylation, mediated by oxidative stress and not catalyzed by TET enzymes.
Clinical, imaging (fMRI) and biomarkers changes after a high intensity tandem bicycle exercise program in Parkinson disease patients.
Current status: Finished
Recent studies have demonstrated the benefits of exercise in patients with Parkinson disease (PD); However, the mechanisms that cause this positive impact are not fully known and further research is needed to understand what type of exercise would be the one to recommend for these patients. This study provided an innovative approach to understand the impact of exercise in PD integrating clinical, biochemical and imaging (functional magnetic resonance (fMRI)) data.
Objective: To identify the Clinical, imaging (fMRI) and biomarkers changes after a four-month high intensity exercise tandem bicycle program in Parkinson disease patients at the This project was financed by University of the Rosario (FIUR), Fundación Santa Fe de Bogotá Clinical Hospital and the University of the Andes.