Network-based Approach in Type 2 Diabetes and Its Cardiovascular Risk

Study Overview
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Brief Summary
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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.

Official Title
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Perturbation of Interactome Through Micro-RNA And Methylome Analyses In Diabetes Endophenotypes: the PIRAMIDE Study Design

Conditions
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Type 2 Diabetes Mellitus, Cardiovascular Diseases

Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: • Patients with known history of cancer, malignancy disorders, active infections, and chronic or immune-mediated diseases.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA methylation status both of CD4+ and CD8+ cells | 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. | 3 Months | 
| Bioinformatics analysis to predict putative novel T2D candidate genes | 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. | 6 Months | 
| RNA sequencing analysis both in CD4+ and CD8+ cells | 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 . | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ROC curves to evaluate putative DNA methylation/microRNA interactions as prognostic biomarkers of cardiovascular dysfunction in T2D patients | 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. | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Network medicine, Epigenetics, Diabetes, Cardiovascular risk