To test these assumptions, we propose an initial proof of concept study to evaluate mitochondrial biology in circulating monocytes in normal volunteers, pre-diabetic and diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the progression to type II diabetes. In parallel, gene expression and proteomic analysis will be performed to evaluate whether the development of insulin resistance and diabetes confers a specific modulation in the biological signature of monocytes with disease progression. To delineate these concepts we will evaluate study subjects' glucose tolerance and insulin sensitivity and draw blood to examine peripheral monocytes. Biological readouts will include: 1) the quantification of the mitochondrial genomic and electron transfer chain content; 2) the determination of mitochondrial reactive oxygen species capacity and defenses; 3) the pattern of monocyte differentiation and 4) the unbiased assessment of monocyte gene expression and proteome.