Either increased or decreased ROS generation and either a ROS independent or dependent effect on induction of HIF-1a activity. In order to determine if metals can induce a hypoxic or hypoxic-like state indirectly through known upstream stimulants, we measured ROS production in human THP-1 macrophages. ROS production due to Ti-alloy, Co-alloy particles and Co ion challenge was shown to occur and thus may either cause or contribute to the induction of the HIF-1a associated responses. An important caveat however, is that measurement of ROS by H2DCFDA is prone to autooxidation. Therefore, further investigation using additional ROS markers is underway to determine if metal-induced ROS production has a central role in the metal-debris activated of HIF-1a or whether it merely produced simultaneously and if this type of activation can be mitigated by anti-oxidant mediators. In summary, our in vitro and in vivo data provide evidence that different implant metals induce different levels of hypoxia responses, where Cobalt-alloy soluble and particulate metal debris preferentially induced hypoxia-like pathology resulting in HIF-1a compensatory responses to metal implant debris. These in vitro and in vivo hypoxia-associated responses reported here provides a mechanism that can account for the unusual reactions around some implants that preferentially release Cobalt particles and ions. Given the increasing number of people receiving total joint replacements and the early failures of some designs that release elevated amount of Cobalt, understanding how this occurs is paramount to ensuring the Disorder that frequently presents with co-morbid nonspecific killing reactions but was insufficient as regards specific predatory behavior safety and efficacy of current and future designs. Type 2 diabetes is as much a disease of disordered lipid metabolism as a disease of abnormal glucose metabolism. Failure to balance skeletal muscle lipid uptake and storage in intracellular triacylglycerol with oxidation in mitochondria is implicated in impaired insulin action. Individuals with type 2 diabetes have a reduced plasma adiponectin concentrations, reduced number of mitochondria, and lower skeletal muscle gene/protein expressions of peroxisome proliferator-activated receptor-c coactivator-1a, a key regulator of mitochondrial biogenesis and oxidative metabolism. While increased PGC-1a has been observed with acute exercise in humans, studies examining the effects of chronic exercise training on adiponectin and PGC-1a and their relationship to the change in glycemic control in individuals with type 2 diabetes are absent. We recently demonstrated in the Health Benefits of Aerobic and Resistance Training in individuals with type 2 Diabetes study that 9 months of combined aerobic and resistance training significantly reduced HbA1C levels in individuals with type 2 diabetes. The HART-D study also included AT only and RT only training groups that, together with the combined AT and RT training group, provide a unique opportunity to examine the influence of factors known to influence glycemic control, specifically serum FFA and adiponectin, skeletal muscle PGC-1a protein content, and anthropometric/demographic measures.