| Outcome Measures: |
Primary: Change in GLP-1 (glucagon like peptide) and GIP (gastric inhibitory peptide) postprandial secretion, The primary endpoint of the study is the change in postprandial GLP-1(ng/ml) and GIP (ng/ml) secretion with metformin treatment compared to placebo., 4 months | Secondary: Change in glycemic variability pre- and post- treatment, A continuous glucose-monitoring device will be attached to each participant and record daily glucose measurements (mg/dl) for 6 consecutive days on two separate time points: a) within a week prior to randomization and b) as a follow up, within a week prior to Inpatient Visit 2., 4 months|Metabolomic profile of each treatment group, Untargeted metabolomics analysis and identification of candidate metabolites using mass spectrometry. Quantitative targeted metabolomics will then be applied on candidate metabolites to compare differences pre and post treatment between metformin and placebo treatment arm, 4 months|Change in inflammatory state, Corrrelation of CRP levels (mg/dl) and treatment arm, as marker of inflammation. CRP will be measured from plasma blood samples collected during Inpatient Visits 1 and 2., 4 months|Change in endothelial dysfunction, Correlation of Serpin E1/PAI-1 levels (ng/ml), VEGF levels (pg/ml), ICAM1 levels (ng/ml) SYndecan-1 levels (ng/ml) and placebo/metformin administration, as markers of endothelial dysfunction. Concentration of adhesion molecules will be measured and compared from plasma blood samples collected during Inpatient Visits 1 and 2., 4 months|Change in cytokine production, Correlation of TNFα levels (pg/ml) ,IL-6 levels (pg/ml),IL-1β levels (pg/ml),IL-10 levels ,(pg/ml) and placebo/metformin administration, as markers of inflammation. Concentration of cytokines will be measured and compared from plasma blood samples collected during Inpatient Visits 1 and 2., 4 months|Change in matrix metalloproteinase-9 (MMP-9) levels, Correlation of MMP-9 levels (ng/ml) levels and placebo/metformin administration, as markers of inflammation. Concentration of MMP-9 will be measured and compared from plasma blood samples collected during Inpatient Visits 1 and 2., 4 months|Change in chemokine production, Correlation of CCL2 levels (pg/ml) ,CCL3 levels (pg/ml),CCL4 levels (pg/ml) and placebo/metformin administration, as markers of inflammation. Concentration chemokines will be measured and compared from plasma blood samples collected during Inpatient Visits 1 and 2., 4 months|Change in gene expression, RNA from PBMCs collected pre and post intervention will be isolated and Quantitative Real Time PCR will be used to measure the transcription of genes related to inflammation and endothelial function., 4 months|Change in gut microbiome analysis, Stool samples will be collected pre and post the intervention on Inpatient Visits 1 and 2 to identify the changes in the microbiome composition based on phylogenetic analysis of the 16S rRNA gene sequencing classification using quantitative PCR., 4 months
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