Cardiovascular Diseases, Type 2 Diabetes Mellitus
Conditions
Keywords
Network medicine, Epigenetics, Diabetes, Cardiovascular risk
Brief summary
PIRAMIDE study design will test the hypothesis that simultaneous interactions between DNA methylation and microRNAs may hit T2D candidate genes and predict the development of T2D-related cardiovascular complications.
Interventions
None listed
Sponsors
Study design
Eligibility
Exclusion criteria
* Clinical Diagnosis of Type 2 Diabetes. In according to current guidelines, diabetes is diagnosed by evidence of impairing fast glucose (IFG) \> 7.0 mmol/L (\>125 mg/dl), post prandial glycemia \> 11.1 mmol/L (\>200 mg/dl), and evidence of glycated hemoglobin (HbA1c) \> 6.6%. Clinical and demographic characteristics of study population will be avaiable from datasets generated by physicians. * Clinical Diagnosis of macrovascular dysfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DNA methylation status both of CD4+ and CD8+ cells | 3 Months | Using Methylation 27K BeadChip platform based on Bisulfite conversion technology, DNA methylation profile of 35 preselected T2D patients will be measured both in CD4+ and CD8+ cells collected from peripheral blood respect with controls. |
| Bioinformatics analysis to predict putative novel T2D candidate genes | 6 Months | The network-based algorithm Weighted Human DNA methylation PPI network (WMPN) will be applied to methylome data in order to obtain a disease module containing the crucial differentially methylated genes both in CD4+ and CD8+ cells from T2D patients and controls. |
| RNA sequencing analysis both in CD4+ and CD8+ cells | 3 Months | RNA sequencing analysis by using Illumina HiSeq2000 Next Generatin Sequencing (NGS) platform will be performed for identifying differentially expressed micro-RNA and mRNA target both in CD4+ and CD8+ cells isolated from T2D patients and controls . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ROC curves to evaluate putative DNA methylation/microRNA interactions as prognostic biomarkers of cardiovascular dysfunction in T2D patients | 12 Months | The ROC curves will be used to correlation putative epigenetics interactions (DNA methylation and microRNA) with the presence or absence of T2D-related cardiovascular dysfunction. |
Countries
Italy